ORCID Profile
0000-0001-8328-9126
Current Organisations
University of Pisa
,
University of Milan
,
European Institute of Oncology
,
Thermo Fisher Scientific Inc
,
Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Basic Pharmacology | Biochemistry and Cell Biology | Receptors and Membrane Biology | Structural Biology (incl. Macromolecular Modelling) |
Expanding Knowledge in the Chemical Sciences | Human Pharmaceutical Treatments (e.g. Antibiotics) | Expanding Knowledge in Technology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2017
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478804
Abstract: Baseline characteristics of studied c-TREnd biomarker population - including all patients with at least one s le available for analysis at any timepoint(s), compared to the overall original TREnd cohort. Fisher exact test was used to calculate p-values. *Denotes patients included in intention-to-treat population of TREnd, despite breach of eligibility criteria (discovered post-enrolment).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6528728
Abstract: AbstractPurpose: The i FGFR1 /i gene is lified in 14% of patients with HR b sup + /sup /b /HER2 b sup − /sup /b breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed. Patients and Methods: Patients with HR b sup + /sup /b /HER2 b sup − /sup /b metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) i FGFR1 /i lified, (ii) i FGFR1 /i non lified, 11q13 lified, and (iii) i FGFR1 /i and 11q13 non lified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. i FGFR1 /i copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high i FGFR1 /i lification (≥4 CNV) than those without high lification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR b sup + /sup /b /HER2 b sup − /sup /b MBC. Although based on small s le sizes, exploratory biomarker analyses suggested that patients with high i FGFR1 /i lification or expression might derive greater benefit. /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540795
Abstract: File with the supplementary material & methods, supplementary tables and supplementary figure.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478804.V1
Abstract: Baseline characteristics of studied c-TREnd biomarker population - including all patients with at least one s le available for analysis at any timepoint(s), compared to the overall original TREnd cohort. Fisher exact test was used to calculate p-values. *Denotes patients included in intention-to-treat population of TREnd, despite breach of eligibility criteria (discovered post-enrolment).
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540798
Abstract: Supplementary file with the listing of the liver genes excluded from transcriptomic analyses.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.CCELL.2019.03.007
Abstract: Tumor cells may adapt to metabolic challenges by alternating between glycolysis and oxidative phosphorylation (OXPHOS). To target this metabolic plasticity, we combined intermittent fasting, a clinically feasible approach to reduce glucose availability, with the OXPHOS inhibitor metformin. In mice exposed to 24-h feeding/fasting cycles, metformin impaired tumor growth only when administered during fasting-induced hypoglycemia. Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3β (GSK3β) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death. Mechanistically, specific activation of the PP2A-GSK3β axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56δ by low glucose, leading to an active PP2A-B56δ complex with high affinity toward GSK3β.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6549478.V1
Abstract: Abstract AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 targeted gene sequencing, 152 RNA sequencing, 67 single nucleotide polymorphism arrays), we found a driver role for i GATA1 /i and i MEN1 /i somatic mutations. Metastases were enriched in i ESR1, PTEN, CDH1, PIK3CA /i , and i RB1 /i mutations i MDM4 /i and i MYC /i lifications and i ARID1A /i deletions. An increase in clonality was observed in driver genes such as i ERBB2 /i and i RB1 /i . Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-enriched switching was associated with i TP53 /i and/or i PIK3CA /i mutations. Metastases had lower immune score and increased immune-permissive cells. High tumor mutational burden correlated to shorter time to relapse in HR sup + /sup /HER2 sup − /sup cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could affect treatment strategies in MBC. Significance: The AURORA program, through the genomic and transcriptomic analyses of matched primary and metastatic s les from 381 patients with breast cancer, coupled with prospectively collected clinical data, identified genomic alterations enriched in metastases and prognostic biomarkers. ESCAT tier I/II alterations were detected in more than half of the patients. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-11-11-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 2659 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540795.V1
Abstract: File with the supplementary material & methods, supplementary tables and supplementary figure.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530048.V1
Abstract: AbstractPurpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both i in vitro /i and in patients with ABC. Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor–positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the “To Reverse ENDocrine Resistance” (TREnd) trial ( i n /i = 46). Results: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients ( i n /i = 8) showing an increase—correlating with a worse outcome than those with decreased/stable TKa ( i n /i = 33 mPFS 3.0 vs 9.0 months i P /i = 0.002). At T2, mTKa was 251 Du/L patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months i P /i = 0.05). Conclusions: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib. /
Publisher: Elsevier BV
Date: 02-2017
Abstract: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Association for Cancer Research (AACR)
Date: 05-2020
DOI: 10.1158/1078-0432.CCR-19-3271
Abstract: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor–positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the “To Reverse ENDocrine Resistance” (TREnd) trial (n = 46). Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients (n = 8) showing an increase—correlating with a worse outcome than those with decreased/stable TKa (n = 33 mPFS 3.0 vs 9.0 months P = 0.002). At T2, mTKa was 251 Du/L patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months P = 0.05). TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib.
Publisher: American Association for Cancer Research (AACR)
Date: 28-06-2021
DOI: 10.1158/2159-8290.CD-20-1647
Abstract: The AURORA program, through the genomic and transcriptomic analyses of matched primary and metastatic s les from 381 patients with breast cancer, coupled with prospectively collected clinical data, identified genomic alterations enriched in metastases and prognostic biomarkers. ESCAT tier I/II alterations were detected in more than half of the patients. This article is highlighted in the In This Issue feature, p. 2659
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6528728.V1
Abstract: AbstractPurpose: The i FGFR1 /i gene is lified in 14% of patients with HR b sup + /sup /b /HER2 b sup − /sup /b breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed. Patients and Methods: Patients with HR b sup + /sup /b /HER2 b sup − /sup /b metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) i FGFR1 /i lified, (ii) i FGFR1 /i non lified, 11q13 lified, and (iii) i FGFR1 /i and 11q13 non lified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. i FGFR1 /i copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high i FGFR1 /i lification (≥4 CNV) than those without high lification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR b sup + /sup /b /HER2 b sup − /sup /b MBC. Although based on small s le sizes, exploratory biomarker analyses suggested that patients with high i FGFR1 /i lification or expression might derive greater benefit. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530048
Abstract: AbstractPurpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both i in vitro /i and in patients with ABC. Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor–positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the “To Reverse ENDocrine Resistance” (TREnd) trial ( i n /i = 46). Results: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients ( i n /i = 8) showing an increase—correlating with a worse outcome than those with decreased/stable TKa ( i n /i = 33 mPFS 3.0 vs 9.0 months i P /i = 0.002). At T2, mTKa was 251 Du/L patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months i P /i = 0.05). Conclusions: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib. /
Publisher: American Association for Cancer Research (AACR)
Date: 2013
DOI: 10.1158/1078-0432.CCR-11-2701
Abstract: The immune system could mediate the antitumor activity of several anticancer treatments. Several chemotherapy compounds, including anthracyclines and oxaliplatin, induce immunogenic cell death that in turn activates antitumor immune response. Trastuzumab induces antibody-dependant cell-mediated cytotoxicity. On the basis of this background, immune markers have recently been the focus of intense translational research to predict and monitor the efficacy of treatments. Gene expression arrays and immunohistochemistry have assessed immune activation and infiltration by macrophages, natural killer, and T and B lymphocytes. Using these approaches, several retrospective analyses of large trials have shown that activation of immune pathway may predict treatment efficacy and outcome in patients with breast cancers. As ex les, intratumoral infiltration by lymphocytes and interferon-response in primary tumor predicted the efficacy of neoadjuvant chemotherapy. Intratumoral infiltration by lymphocytes was associated with good prognosis in patients with triple-negative breast cancer treated with adjuvant chemotherapy. More recently, it has been suggested that lymphocyte infiltration could also predict efficacy of trastuzumab. Finally, small retrospective studies have suggested that postchemotherapy lymphocyte infiltrates could be associated with better outcome in patients who did not reach pathologic complete response. This body of evidence suggests that assessing immune infiltration and activation could be useful in the future to stratify breast cancer patients. In addition, they provide evidence for the development of immunotherapies in breast cancer patients. Clin Cancer Res 19(1) 28–. ©2012 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540798.V1
Abstract: Supplementary file with the listing of the liver genes excluded from transcriptomic analyses.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1038/S41523-020-0155-1
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
DOI: 10.1038/S41523-020-0156-0
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues scoring outside the tumor boundary tumors with minimal assessable stroma including lymphocytes associated with other structures and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at itfalls .
Publisher: American Association for Cancer Research (AACR)
Date: 15-01-2020
DOI: 10.1158/1078-0432.CCR-19-1164
Abstract: The FGFR1 gene is lified in 14% of patients with HR+/HER2− breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed. Patients with HR+/HER2− metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 lified, (ii) FGFR1 non lified, 11q13 lified, and (iii) FGFR1 and 11q13 non lified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC. Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%–35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%–18%) and 15% (95% CI, 6%–34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 lification (≥4 CNV) than those without high lification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers. Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR+/HER2− MBC. Although based on small s le sizes, exploratory biomarker analyses suggested that patients with high FGFR1 lification or expression might derive greater benefit.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22474223.V1
Abstract: Supplementary Table S1. Treatment dose, duration, interruption and reduction. Supplementary Table S2A. Performance of the FGF23 ELISA, Kainos Laboratories Inc., cat# CY4000. Supplementary Table S2B. Concentration range of FGF23 in serum and plasma s les. Supplementary Table S2C. ddPCR assays used for determination of FGFR1 CNV. Supplementary Figure S1. A) FINESSE study design. B) Supplementary Figure S1B. FINESSE CONSORT diagram. Supplementary Figure S2. FISH screening results for FGFR1, CCND1/11q and FGF3,4,19. All s les were screened for both FGFR1 and CCND1/11q. Only s les positive for CCND1/11q lification were assessed for FGF3,4,19 lification. Of these, 1 patient was not assessed for FGF3,4,19 at the request of the site. 3 patients assessed as FGF3,4,19 lified by additional evalution criteria to those described in the Methods section, with % of tumour cells showing {greater than or equal to}5 gene signals/nucleus. Supplementary Figure S3. Progression-free survival by A) FGFR1 lification status by FISH and B) FGFR1 expression by IHC. Supplementary Figure S4. Expression of endothelial FGF2 and Ki67 presented by trial cohort. Supplementary Figure S5. Progression free survival by A) endothelial FGF2 and B) endothelial Ki67 expression.
Publisher: Elsevier BV
Date: 03-2019
Abstract: Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival. All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs. Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile. ClinicalTrials.gov, NCT02447003.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22474223
Abstract: Supplementary Table S1. Treatment dose, duration, interruption and reduction. Supplementary Table S2A. Performance of the FGF23 ELISA, Kainos Laboratories Inc., cat# CY4000. Supplementary Table S2B. Concentration range of FGF23 in serum and plasma s les. Supplementary Table S2C. ddPCR assays used for determination of FGFR1 CNV. Supplementary Figure S1. A) FINESSE study design. B) Supplementary Figure S1B. FINESSE CONSORT diagram. Supplementary Figure S2. FISH screening results for FGFR1, CCND1/11q and FGF3,4,19. All s les were screened for both FGFR1 and CCND1/11q. Only s les positive for CCND1/11q lification were assessed for FGF3,4,19 lification. Of these, 1 patient was not assessed for FGF3,4,19 at the request of the site. 3 patients assessed as FGF3,4,19 lified by additional evalution criteria to those described in the Methods section, with % of tumour cells showing {greater than or equal to}5 gene signals/nucleus. Supplementary Figure S3. Progression-free survival by A) FGFR1 lification status by FISH and B) FGFR1 expression by IHC. Supplementary Figure S4. Expression of endothelial FGF2 and Ki67 presented by trial cohort. Supplementary Figure S5. Progression free survival by A) endothelial FGF2 and B) endothelial Ki67 expression.
Location: United States of America
Location: Italy
Start Date: 03-2021
End Date: 03-2026
Amount: $4,789,838.00
Funder: Australian Research Council
View Funded Activity