ORCID Profile
0000-0002-3611-0258
Current Organisation
Guangdong Provincial People's Hospital
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Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JTHO.2015.11.014
Abstract: Metastatic spread to the brain is common in patients with non-small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutation-positive patients with NSCLC and included patients with brain metastases prespecified subgroup analyses are assessed in this article. For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378 LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months HR, 0.50 p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases.
Publisher: Elsevier BV
Date: 04-2016
Publisher: American Association for Cancer Research (AACR)
Date: 2022
DOI: 10.1158/1078-0432.CCR-21-3530
Abstract: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB–IIIA EGFR-mutated (EGFRm) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB–IIIA N = 682). Clinically meaningful changes were defined using the SF-36 manual. Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46–47) and maintained to Week 96, with no clinically meaningful differences between arms difference in adjusted least squares (LS) mean [95% confidence intervals (CI), −1.18 (−2.02 to −0.34) and −1.34 (−2.40 to −0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS HR, 1.17 (95% CI, 0.82–1.67) and HR, 0.98 (95% CI, 0.70–1.39), respectively. HRQoL was maintained with adjuvant osimertinib in patients with stage IB–IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488171
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717520
Abstract: Kaplan–Meier estimates showing investigator-assessed PFS in FLAURA trial patients by clearance or non-clearance of plasma EGFRm status at Weeks 3 or 6 in patients who had baseline detectable plasma EGFRm. For comparison, patients with baseline non-detectable plasma EGFRm are included. A, Osimertinib arm by Week 3 plasma EGFRm status (n = 238). B, Comparator EGFR-TKI arm by Week 3 plasma EGFRm status (n = 243). C, Osimertinib arm by Week 6 plasma EGFRm status (n = 240). D, Comparator EGFR-TKI arm by Week 6 plasma EGFRm status (n = 235). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NC, not calculable mPFS, median PFS TKI, tyrosine kinase inhibitor.
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717523
Abstract: FLAURA flow diagram for ctDNA analysis (n = 499). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 3 patients in the osimertinib arm and 7 patients in the comparator EGFR-TKI arm without a valid ddPCR result at Weeks 3 and 6 these s les were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) TKI, tyrosine kinase inhibitor.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488174
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488177
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.C.6752094.V1
Abstract: AbstractPurpose: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non–small cell lung cancer (NSCLC) monitoring dynamic ctDNA changes may be used to predict outcomes. Patients and Methods: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm ex19del or L858R) advanced NSCLC AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR–tyrosine kinase inhibitor (EGFR-TKI gefitinib/erlotinib FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma i EGFR /i m was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma i EGFR /i m and plasma i EGFR /i m clearance (non-detection) at Weeks 3/6. Results: In AURA3 ( i n /i = 291), non-detectable versus detectable baseline plasma i EGFR /i m had longer median progression-free survival [mPFS HR, 0.48 95% confidence interval (CI), 0.33–0.68 i P /i 0.0001]. In patients with Week 3 clearance versus non-clearance ( i n /i = 184), respectively, mPFS (months 95% CI) was 10.9 (8.3–12.6) versus 5.7 (4.1–9.7) with osimertinib and 6.2 (4.0–9.7) versus 4.2 (4.0–5.1) with platinum-pemetrexed. In FLAURA ( i n /i = 499), mPFS was longer with non-detectable versus detectable baseline plasma i EGFR /i m (HR, 0.54 95% CI, 0.41–0.70 i P /i 0.0001). For Week 3 clearance versus non-clearance ( i n /i = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5–16.5) with osimertinib and 10.8 (9.7–11.1) versus 7.0 (5.6–8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance. Conclusions: Plasma i EGFR /i m analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC. /
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717526
Abstract: Assessment of correlation between EGFRm VAF in baseline plasma and investigator-assessed PFS in A, patients from the AURA3 trial, by treatment arm and B, patients from the FLAURA trial, by treatment arm. Abbreviations: CR, complete response EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NE, not evaluable PD, progressive disease PFS, progression-free survival PR, partial response SD, stable disease VAF, variant allelic fraction.
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717529
Abstract: Kaplan–Meier estimates showing OS in all trial patients with a valid baseline (detectable or non-detectable) plasma ctDNA result in A, patients from the AURA3 trial (n = 291) and B, patients from the FLAURA trial (n = 499). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) HR, hazard ratio mOS, median overall survival NC, not calculable.
Publisher: Oxford University Press (OUP)
Date: 02-02-2017
DOI: 10.1093/JNCI/DJW279
Abstract: We performed an in idual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided. Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P = .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P = .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P < .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7). Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: Archives of Pathology and Laboratory Medicine
Date: 05-2018
DOI: 10.5858/ARPA.2017-0245-RA
Abstract: The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, in conjunction with the International Mesothelioma Interest Group, the International Thymic Malignancy Interest Group, and the Worldwide Esophageal Cancer Collaboration, developed proposals for the 8th edition of their respective tumor, node, metastasis (TNM) staging classification systems. To review these changes and discuss issues for the reporting pathologist. Proposals were based on international databases of lung (N = 94 708), with an external validation using the US National Cancer Database mesothelioma (N = 3519) thymic epithelial tumors (10 808) and epithelial cancers of the esophagus and esophagogastric junction (N = 22 654). These proposals have been mostly accepted by the Union for International Cancer Control and the American Joint Committee on Cancer and incorporated into their respective staging manuals (2017). The Union for International Cancer Control recommended implementation beginning in January 2017 however, the American Joint Committee on Cancer has deferred deployment of the eighth TNM until January 1, 2018, to ensure appropriate infrastructure for data collection. This manuscript summarizes the updated staging of thoracic malignancies, specifically highlighting changes from the 7th edition that are relevant to pathologic staging. Histopathologists should become familiar with, and start to incorporate, the 8th edition staging in their daily reporting of thoracic cancers henceforth.
Publisher: Elsevier BV
Date: 06-0001
DOI: 10.1016/J.JTHO.2018.03.010
Abstract: Traditionally, marked tumor shrinkage has been assumed to portend better outcome. We investigated whether depth of tumor response was associated with improved survival outcomes in advanced EGFR-mutant NCLC. In idual patient data from randomized trials (EURTAC, IPASS, ENSURE, LUX-Lung 3, and LUX-Lung 6) were used. The association of depth of response with progression-free survival (PFS) and overall survival was examined using landmark analyses. Depth of response based on radiologic assessments at 6 weeks and 12 weeks was calculated as the relative changes in the sum of the longest diameters of the target lesions from baseline. Of 1081 evaluable patients at 6 weeks with no disease progression, 71.2% achieved Response Evaluation Criteria in Solid Tumors response. Using a landmark analysis, EGFR-TKI was more effective than chemotherapy (PFS hazard ratio = 0.36, p < .0001) and was associated with greater mean tumor shrinkage than chemotherapy (35.1% versus 18.5%, p < .0001). However, there was no significant difference in the relative PFS benefit between treatment groups across the entire spectrum of tumor shrinkage (p = .18 for test of interaction between treatment and continuously measured depth of response). Depth of response at 6 weeks was not associated with PFS when adjusted for treatment effect (hazard ratio = 0.96, p = .78). Similar results were obtained for 12-week landmark analysis and for OS outcome. The PFS advantage of EGFR-TKI over chemotherapy in advanced EGFR mutant NCLC is not explained by depth of response at 6 or 12 weeks. It should not be used as a surrogate of benefit in future trials or routine clinical decision making.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
DOI: 10.1158/1078-0432.C.6752094
Abstract: AbstractPurpose: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non–small cell lung cancer (NSCLC) monitoring dynamic ctDNA changes may be used to predict outcomes. Patients and Methods: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm ex19del or L858R) advanced NSCLC AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR–tyrosine kinase inhibitor (EGFR-TKI gefitinib/erlotinib FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma i EGFR /i m was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma i EGFR /i m and plasma i EGFR /i m clearance (non-detection) at Weeks 3/6. Results: In AURA3 ( i n /i = 291), non-detectable versus detectable baseline plasma i EGFR /i m had longer median progression-free survival [mPFS HR, 0.48 95% confidence interval (CI), 0.33–0.68 i P /i 0.0001]. In patients with Week 3 clearance versus non-clearance ( i n /i = 184), respectively, mPFS (months 95% CI) was 10.9 (8.3–12.6) versus 5.7 (4.1–9.7) with osimertinib and 6.2 (4.0–9.7) versus 4.2 (4.0–5.1) with platinum-pemetrexed. In FLAURA ( i n /i = 499), mPFS was longer with non-detectable versus detectable baseline plasma i EGFR /i m (HR, 0.54 95% CI, 0.41–0.70 i P /i 0.0001). For Week 3 clearance versus non-clearance ( i n /i = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5–16.5) with osimertinib and 10.8 (9.7–11.1) versus 7.0 (5.6–8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance. Conclusions: Plasma i EGFR /i m analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488177.V1
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: Elsevier BV
Date: 09-2018
Abstract: In clinical trials of patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) treated with crizotinib, evaluation of the relationship between the percentage of ALK-positive cells by fluorescence in situ hybridization (FISH)-particularly near the cut-off defining positive status-and clinical outcomes have been limited by small s le sizes. Data were pooled from three large prospective trials (one single-arm and two randomized versus chemotherapy) of crizotinib in patients with ALK-positive NSCLC determined by Vysis ALK Break Apart FISH using a cut-off of ≥15% ALK-positive cells. Logistic regression and proportional hazards regression analyses were used to explore the association of percent ALK-positive cells with objective response and progression-free survival (PFS), respectively. Of 11 081 screened patients, 1958 (18%) were ALK positive, 7512 (68%) were ALK negative, and 1540 (14%) were uninformative. Median percentage of ALK-positive cells was 58% in ALK-positive patients and 2% in ALK-negative patients. Of ALK-positive patients, 5% had 15%-19% ALK-positive cells of ALK-negative patients, 2% had 10%-14% ALK-positive cells. Objective response rate for ALK-positive, crizotinib-treated patients with ≥20% ALK-positive cells was 56% (n = 700/1246), 55% (n = 725/1312) for those with ≥15% ALK-positive cells, and 38% for those with 15%-19% ALK-positive cells (n = 25/66). As a continuous variable, higher percentages of ALK-positive cells were estimated to be associated with larger differences in objective response and PFS between crizotinib and chemotherapy however, tests for interaction between treatment and percentage of ALK-positive cells were not significant (objective response, P = 0.054 PFS, P = 0.17). Patients with ALK-positive NSCLC benefit from treatment with crizotinib across the full range of percentage of ALK-positive cells, supporting the clinical utility of the 15% cut-off. The small number of patients with scores near the cut-off warrant additional study given the potential for misclassification of ALK status due to technical or biologic reasons.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6532659.V1
Abstract: AbstractPurpose: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB–IIIA EGFR-mutated ( i EGFR /i m) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. Patients and Methods: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB–IIIA i N /i = 682). Clinically meaningful changes were defined using the SF-36 manual. Results: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46–47) and maintained to Week 96, with no clinically meaningful differences between arms difference in adjusted least squares (LS) mean [95% confidence intervals (CI), −1.18 (−2.02 to −0.34) and −1.34 (−2.40 to −0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS HR, 1.17 (95% CI, 0.82–1.67) and HR, 0.98 (95% CI, 0.70–1.39), respectively. Conclusions: HRQoL was maintained with adjuvant osimertinib in patients with stage IB–IIIA i EGFR /i m NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. i See related commentary by Patil and Bunn, p. 2204 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-06-2015
Abstract: We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non–small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy. This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided. In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48 95% CI, 0.39 to 0.58 P interaction .001). Never-smokers had a 36% greater benefit (HR, 0.32 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50 95% CI, 0.40 to 0.63 P interaction .001). Women had a 27% greater benefit (HR, 0.33 95% CI, 0.28 to 0.38) than men (HR, 0.45 95% CI, 0.36 to 0.55 treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs. Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717529.V1
Abstract: Kaplan–Meier estimates showing OS in all trial patients with a valid baseline (detectable or non-detectable) plasma ctDNA result in A, patients from the AURA3 trial (n = 291) and B, patients from the FLAURA trial (n = 499). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) HR, hazard ratio mOS, median overall survival NC, not calculable.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488168.V1
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 28-06-2023
DOI: 10.1158/1078-0432.CCR-22-3146
Abstract: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non–small cell lung cancer (NSCLC) monitoring dynamic ctDNA changes may be used to predict outcomes. This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm ex19del or L858R) advanced NSCLC AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR–tyrosine kinase inhibitor (EGFR-TKI gefitinib/erlotinib FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6. In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS HR, 0.48 95% confidence interval (CI), 0.33–0.68 P & 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months 95% CI) was 10.9 (8.3–12.6) versus 5.7 (4.1–9.7) with osimertinib and 6.2 (4.0–9.7) versus 4.2 (4.0–5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54 95% CI, 0.41–0.70 P & 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5–16.5) with osimertinib and 10.8 (9.7–11.1) versus 7.0 (5.6–8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance. Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488165.V1
Abstract: Supplementary Table from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: Springer Science and Business Media LLC
Date: 27-02-2023
DOI: 10.1038/S41467-023-35962-X
Abstract: Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma s les collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have resistance-related genomic alteration MET lification (14/78, 18%) and EGFR C797X mutation (14/78, 18%).
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717532
Abstract: Correlation between EGFRm allelic fraction at baseline by ddPCR (Biodesix) and NGS (Guardant Health) analyses in A, patients from the AURA3 trial (n = 202) and B, patients from the FLAURA trial (n = 347). Abbreviations: ddPCR, droplet digital PCR EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NGS, next-generation sequencing.
Publisher: Massachusetts Medical Society
Date: 16-02-2017
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2022
DOI: 10.1200/JCO.21.02278
Abstract: Lorlatinib significantly improved progression-free survival (PFS) versus crizotinib and showed robust intracranial activity in patients with previously untreated advanced ALK-positive non–small-cell lung cancer (NSCLC) in the phase III CROWN trial. Here, we report post hoc efficacy outcomes in patients with and without brain metastases at baseline, and present data on the incidence and management of CNS adverse events (AEs) in CROWN. Eligible patients were randomly assigned 1:1 to first-line lorlatinib (100 mg once daily) or crizotinib (250 mg twice a day) no crossover between treatment arms was permitted. Tumor assessments, including CNS magnetic resonance imaging, were performed at screening and then at 8-week intervals. Regular assessments of patient-reported outcomes were conducted. PFS by blinded independent central review was improved with lorlatinib versus crizotinib in patients with and without brain metastases at baseline (12-month PFS rates: 78% v 22% and 78% v 45%, respectively). Lorlatinib was associated with lower 12-month cumulative incidence of CNS progression versus crizotinib in patients with (7% v 72%) and without (1% v 18%) brain metastases at baseline. In total, 35% of patients had CNS AEs with lorlatinib, most of grade 1 severity. Occurrence of CNS AEs did not result in a clinically meaningful difference in patient-reported quality of life. At analysis, 56% of CNS AEs had resolved (33% without intervention 17% with lorlatinib dose modification), and 38% were unresolved most required no intervention. Lorlatinib dose modification did not notably influence PFS. First-line lorlatinib improved PFS outcomes and reduced CNS progression versus crizotinib in patients with advanced ALK-positive non–small-cell lung cancer with or without brain metastases at baseline. Half of all CNS AEs resolved without intervention or with lorlatinib dose modification.
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717520.V1
Abstract: Kaplan–Meier estimates showing investigator-assessed PFS in FLAURA trial patients by clearance or non-clearance of plasma EGFRm status at Weeks 3 or 6 in patients who had baseline detectable plasma EGFRm. For comparison, patients with baseline non-detectable plasma EGFRm are included. A, Osimertinib arm by Week 3 plasma EGFRm status (n = 238). B, Comparator EGFR-TKI arm by Week 3 plasma EGFRm status (n = 243). C, Osimertinib arm by Week 6 plasma EGFRm status (n = 240). D, Comparator EGFR-TKI arm by Week 6 plasma EGFRm status (n = 235). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NC, not calculable mPFS, median PFS TKI, tyrosine kinase inhibitor.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JTHO.2017.05.019
Abstract: Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488165
Abstract: Supplementary Table from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717535
Abstract: AURA3 flow diagram for ctDNA analysis (n = 291). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 9 patients in the osimertinib arm and 1 patient in the platinum-pemetrexed arm without a valid ddPCR result at Weeks 3 and 6 these s les were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA EGFRm, epidermal growth factor receptor mutation (ex19del or L858R).
Publisher: Elsevier BV
Date: 09-2015
Publisher: Massachusetts Medical Society
Date: 20-06-2013
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488171.V1
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488168
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.LUNGCAN.2018.10.027
Abstract: In AURA3 (NCT02151981), osimertinib treatment provided significant clinical benefit compared with platinum-pemetrexed in patients with epidermal growth factor receptor (EGFR) T790M-positive advanced non-small-cell lung cancer (NSCLC), whose tumors had progressed on previous EGFR-tyrosine kinase inhibitor therapy. This retrospective analysis investigated detection rates for T790M, common (exon 19 deletion and L858R), and rare EGFR mutations in tissue s les from the screened population of AURA3. In AURA3, eligible patients were randomized 2:1 to receive oral osimertinib 80 mg once daily or intravenous platinum-pemetrexed every 3 weeks for up to six cycles. Tumor tissue s les were centrally tested for EGFR mutations using the cobas A total of 820 screened patients had a valid EGFR mutation test result, of whom 452 (55%) were T790M-positive. Detection rates were similar by ethnicity (Asian versus non-Asian) for T790M (53% versus 58%) and exon 19 deletions (56% versus 63%). Conversely, the L858R rate was higher among Asian patients versus non-Asian patients (39% versus 28% p = 0.0017). In the overall population, a higher proportion of patients had T790M detected against a background of exon 19 deletion versus L858R mutations (64% versus 47% p < 0.0001). Rare EGFR mutations were detected in 28 (3%) patients, including G719X (2%), exon 20 insertion (1%), and S768I (<1%). Among AURA3 screened patients with EGFR mutation-positive advanced NSCLC, approximately half had detectable T790M in their tumor tissue, a rate unaffected by ethnicity. Results are consistent with previous reports of T790M detection rate in this patient population.
Publisher: Springer Science and Business Media LLC
Date: 24-11-2017
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.LUNGCAN.2019.04.014
Abstract: With the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), sequential therapy could potentially render EGFR mutation-positive non-small cell lung cancer a chronic disease in some patients. In this retrospective analysis of EGFR mutation-positive (Del19/L858R) patients receiving first-line afatinib in LUX-Lung 3, 6, and 7, we assessed uptake of, and outcomes following, subsequent therapies including the third-generation EGFR TKI, osimertinib. Post-progression therapy data were prospectively collected during follow-up. Molecular testing of tumours at progression/discontinuation of afatinib was not mandatory. Duration of subsequent therapies, and survival following osimertinib, were calculated with Kaplan-Meier estimates. Among 553 patients who discontinued first-line afatinib, second-, third- and fourth-line therapy was administered in 394 (71%), 265 (48%), and 156 (28%) patients. The most common post-progression therapy was platinum-based chemotherapy (46%). Thirty-seven patients received subsequent osimertinib, 10 as second-line treatment. Median progression-free survival on afatinib in these 37 patients was 21.9 months. Median duration of osimertinib therapy was 20.2 months median overall survival was not reached after a median follow-up of 4.7 years. Most patients treated with first-line afatinib received subsequent therapy. Although limited by s le size, enrichment, and a retrospective nature, data from patients who received sequential afatinib and osimertinib are encouraging, warranting further investigation.
Publisher: Massachusetts Medical Society
Date: 04-12-2014
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-09-2023
DOI: 10.1200/JCO.23.01476
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717514.V1
Abstract: Univariable and multivariable analyses for OS from the AURA3 trial (ctDNA evaluable population, n = 291) and FLAURA trial (ctDNA evaluable population, n = 499).
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JTHO.2017.04.011
Abstract: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717523.V1
Abstract: FLAURA flow diagram for ctDNA analysis (n = 499). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 3 patients in the osimertinib arm and 7 patients in the comparator EGFR-TKI arm without a valid ddPCR result at Weeks 3 and 6 these s les were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) TKI, tyrosine kinase inhibitor.
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717517.V1
Abstract: Representativeness of study participants
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-10-2009
Abstract: This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC). Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m 2 days 1 and 8) and either cisplatin (75 mg/m 2 day 1) or carboplatin (5 × area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety. The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC) -erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47 log-rank P = .0002 median, 29.4 v 23.4 weeks) this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease. Sequential administration of erlotinib following gemcitabine latinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.
Publisher: MDPI AG
Date: 11-01-2023
DOI: 10.3390/NU15020366
Abstract: Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p 0.001 and −1.47 ± 0.20 p 0.001, respectively), which was significantly different from the HabDiet group over time (p 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.CLLC.2018.03.009
Abstract: Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm Treatment-naive patients with advanced EGFRm Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03] LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19 Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm
Publisher: Springer Science and Business Media LLC
Date: 22-12-2016
DOI: 10.1038/BJC.2016.420
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717532.V1
Abstract: Correlation between EGFRm allelic fraction at baseline by ddPCR (Biodesix) and NGS (Guardant Health) analyses in A, patients from the AURA3 trial (n = 202) and B, patients from the FLAURA trial (n = 347). Abbreviations: ddPCR, droplet digital PCR EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NGS, next-generation sequencing.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6532659
Abstract: AbstractPurpose: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB–IIIA EGFR-mutated ( i EGFR /i m) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. Patients and Methods: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB–IIIA i N /i = 682). Clinically meaningful changes were defined using the SF-36 manual. Results: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46–47) and maintained to Week 96, with no clinically meaningful differences between arms difference in adjusted least squares (LS) mean [95% confidence intervals (CI), −1.18 (−2.02 to −0.34) and −1.34 (−2.40 to −0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS HR, 1.17 (95% CI, 0.82–1.67) and HR, 0.98 (95% CI, 0.70–1.39), respectively. Conclusions: HRQoL was maintained with adjuvant osimertinib in patients with stage IB–IIIA i EGFR /i m NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. i See related commentary by Patil and Bunn, p. 2204 /i /
Publisher: Elsevier BV
Date: 02-2015
Publisher: Elsevier BV
Date: 11-2016
Abstract: Afatinib 40 mg/day is approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). In the case of drug-related grade ≥3 or selected prolonged grade 2 adverse events (AEs), the dose can be reduced by 10 mg decrements to a minimum of 20 mg. Here, we evaluate the influence of afatinib dose reduction on AEs, pharmacokinetics and progression-free survival (PFS) in the phase III LUX-Lung 3 and 6 (LL3/6) trials. Treatment-naïve patients with advanced EGFR mutation-positive NSCLC in LL3 (global) and LL6 (China, Thailand, South Korea) were randomized to afatinib or chemotherapy. All afatinib-treated patients (LL3, n = 229 LL6, n = 239) were included in the post hoc analyses. Incidence and severity of common AEs before and after afatinib dose reduction were assessed. Afatinib plasma concentrations were compared in patients who reduced to 30 mg versus those remaining at 40 mg. PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. Dose reductions occurred in 53.3% (122/229) and 28.0% (67/239) of patients in LL3 and LL6, respectively most (86.1% and 82.1%) within the first 6 months of treatment. Dose reduction led to decreases in the incidence of drug-related AEs, and was more likely in patients with higher afatinib plasma concentrations. On day 43, patients who dose reduced to 30 mg (n = 59) had geometric mean afatinib plasma concentrations of 23.3 ng/ml, versus 22.8 ng/ml in patients who remained on 40 mg (n = 284). The median PFS was similar in patients who dose reduced during the first 6 months versus those who did not {LL3: 11.3 versus 11.0 months [hazard ratio (HR) 1.25] LL6: 12.3 versus 11.0 months (HR 1.00)}. Tolerability-guided dose adjustment is an effective measure to reduce afatinib-related AEs without affecting therapeutic efficacy. Clinicaltrials.gov identifiers: NCT00949650 and NCT0112393.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.LUNGCAN.2011.02.017
Abstract: Erlotinib is a highly potent inhibitor of epidermal growth factor receptor tyrosine-kinase activity that significantly prolongs overall survival in patients with non-small-cell lung cancer (NSCLC), and improves symptom control and quality of life compared with placebo. The safety and efficacy of erlotinib has been investigated in a large, international, phase IV, open-label study (TRUST) in patients (n=6665) with advanced stage IIIB/IV NSCLC. An analysis of efficacy and safety outcomes is reported for patients receiving erlotinib as second-line therapy in TRUST (n=3224). Best response data were available for all 3224 patients. Complete response, partial response and stable disease were achieved in 25 (<1%), 368 (14%) and 1444 (54%) patients, respectively, for a disease control rate of 68%. Median progression-free and overall survivals were 13.6 weeks and 8.6 months, respectively 1-year survival was 39.4%. Safety data were available for all patients. Of these, 389 patients (12%) had an erlotinib-related adverse event (AE) other than pre-specified AEs defined in the protocol only 96 patients (3%) had an erlotinib-related AE ≥ grade 3. Of 1376 patients (43%) with serious AEs (SAEs), only 122 (4%) had treatment-related SAEs and most were gastrointestinal disorders (mainly diarrhoea and nausea). No treatment-related SAE occurred in ≥ 1% of patients. Data on the incidence of erlotinib-related rash were collected for all patients, 2302 (71%) of whom experienced rash. Of these rash events, 83% were of grade 1/2. These data confirm the good efficacy and tolerability of second-line erlotinib in a broad range of patients with NSCLC.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717514
Abstract: Univariable and multivariable analyses for OS from the AURA3 trial (ctDNA evaluable population, n = 291) and FLAURA trial (ctDNA evaluable population, n = 499).
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717526.V1
Abstract: Assessment of correlation between EGFRm VAF in baseline plasma and investigator-assessed PFS in A, patients from the AURA3 trial, by treatment arm and B, patients from the FLAURA trial, by treatment arm. Abbreviations: CR, complete response EGFRm, epidermal growth factor receptor mutation (ex19del or L858R) NE, not evaluable PD, progressive disease PFS, progression-free survival PR, partial response SD, stable disease VAF, variant allelic fraction.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 08-2018
Abstract: The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) –positive advanced nonsquamous non–small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 or carboplatin (area under the concentration–time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171). Crossover to crizotinib was permitted after disease progression. OS was analyzed using a stratified log-rank test and a prespecified rank-preserving structural failure time model to account for crossover. Median follow-up duration for OS was approximately 46 months for both arms. In the chemotherapy arm, 144 patients (84.2%) received crizotinib in subsequent lines. Hazard ratio for OS was 0.760 (95% CI, 0.548 to 1.053 two-sided P = .0978). Median OS was not reached (NR) with crizotinib (95% CI, 45.8 months to NR) and 47.5 months with chemotherapy (95% CI, 32.2 months to NR). Survival probability at 4 years was 56.6% (95% CI, 48.3% to 64.1%) with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) with chemotherapy. After crossover adjustment, there was an improvement in OS that favored crizotinib (hazard ratio, 0.346 95% bootstrap CI, 0.081 to 0.718). The longest OS was observed in crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor. No new safety signals were identified. The final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non–small-cell lung cancer and highlights the benefit of crizotinib for prolonging survival in this patient population.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JTHO.2016.03.025
Abstract: This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.
Publisher: Elsevier BV
Date: 12-2015
Publisher: American Association for Cancer Research (AACR)
Date: 20-07-2023
DOI: 10.1158/1078-0432.23717517
Abstract: Representativeness of study participants
Publisher: Elsevier BV
Date: 2016
Publisher: Elsevier BV
Date: 07-2015
Publisher: Korean Cancer Association
Date: 15-07-2018
DOI: 10.4143/CRT.2017.280
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-08-2016
Abstract: Intracranial efficacy of first-line crizotinib versus chemotherapy was compared prospectively in the phase III PROFILE 1014 study in ALK-positive non–small-cell lung cancer. Patients were randomly assigned to receive crizotinib (250 mg twice daily n = 172) or chemotherapy (pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 or carboplatin at area under the curve 5 to 6, every 3 weeks for ≤ six cycles n = 171). Patients with stable treated brain metastases (tBM) were eligible. Intracranial efficacy was assessed at baseline and every 6 or 12 weeks in patients with or without known brain metastases (BM), respectively intracranial time to tumor progression (IC-TTP per protocol) and intracranial disease control rate (IC-DCR post hoc) were measured. The intent-to-treat population was also assessed. Of 343 patients in the intent-to-treat population, 23% had tBM at baseline. A nonsignificant IC-TTP improvement was observed with crizotinib in the intent-to-treat population (hazard ratio [HR], 0.60 P = .069), patients with tBM (HR, 0.45 P = .063), and patients without BM (HR, 0.69 P = .323). Among patients with tBM, IC-DCR was significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%, respectively P .001) and 24 weeks (56% v 25%, respectively P = .006). Progression-free survival was significantly longer with crizotinib versus chemotherapy in both subgroups (tBM present: HR, 0.40 P .001 median, 9.0 v 4.0 months, respectively BM absent: HR, 0.51 P .001 median, 11.1 v 7.2 months, respectively) and in the intent-to-treat population (HR, 0.45 P .001 median, 10.9 v 7.0 months, respectively). Compared with chemotherapy, crizotinib demonstrated a significantly higher IC-DCR in patients with tBM. Improvements in IC-TTP were not statistically significant in patients with or without tBM, although sensitivity to detect treatment differences in or between the two subgroups was low.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22488174.V1
Abstract: Supplementary Figure from Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JTHO.2016.10.003
Abstract: Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
No related grants have been discovered for Yi-Long Wu.