ORCID Profile
0000-0001-8738-8463
Current Organisations
Calvary Mater Newcastle
,
Breast Cancer Trials Ltd
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Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BREAST.2013.12.001
Abstract: Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy. Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety. 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer. Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.
Publisher: Wiley
Date: 06-2016
DOI: 10.1111/IMJ.13049
Abstract: Neoadjuvant systemic therapy (NAST) has become an established treatment option for women with operable breast cancer. We aimed to better understand NAST treatment patterns, barriers and facilitators in Australia and New Zealand. We undertook a cross-sectional survey of the current clinical practice of Australian and New Zealand breast cancer specialists. Questions included referral patterns for NAST, patient selection, logistics, decision making and barriers. Of 207 respondents, 162 (78%) reported routinely offering NAST to selected patients with operable breast cancer (median 9% of patients offered NAST). Specialty, location, practice type, gender or years of experience did not predict for offering NAST. In all, 45 and 58% wanted to increase the number of patients who receive NAST in routine care and in clinical trials respectively. Facilitators included the multidisciplinary team meeting and access to NAST clinical trials. Specialist-reported patient barriers included: patient desire for immediate surgery (63% rated as important/very important) lack of awareness of NAST (50%) concern about progression (43%) and disinterest in downstaging (32%). Forty-three per cent of participants experienced system-related barriers to the use of NAST, including other clinicians' lack of interest (27%) lack of clinical trials (24%) and unacceptable wait for a medical oncology appointment (37%). This group of Australian and New Zealand clinicians are interested in NAST for operable breast cancer in routine care and clinical trials. Patient- and system-related barriers that prevent the optimal uptake of this treatment approach will need to be systematically addressed if NAST is to become a more common approach.
Publisher: Wiley
Date: 10-2019
DOI: 10.1111/IMJ.14456
Abstract: Only 2-3% of cancer patients enrol in a trial. We surveyed patients' willingness to change clinician or treating centre, or to travel, to participate in trials, to improve trial recruitment. Of 188 respondents, 79% were willing to participate in a trial in at least one scenario. Increasing travel time, change in oncologist, private health insurance and out of pocket expenses decreased likelihood of joining a trial. Rural and regional patients, and those from lower socio-economic areas, were more willing to travel. To optimise access to trials, clinicians should refer within and between institutions.
Publisher: JMIR Publications Inc.
Date: 20-05-2016
DOI: 10.2196/RESPROT.5641
Publisher: Oxford University Press (OUP)
Date: 10-01-2012
DOI: 10.1634/THEONCOLOGIST.2011-0300
Abstract: After completing this course, the reader will be able to: Among patients with liver metastases from colorectal cancer, determine which would benefit from liver resection, the timing for surgery, and an appropriate perioperative chemotherapy regimen.Determine which patients are candidates for perioperative chemotherapy and the appropriate timing of chemotherapy, and describe the relevant toxicities and their impact on morbidity and mortality. This article is available for continuing medical education credit at CME.TheOncologist.com Colorectal cancer is a very common malignancy and frequently manifests with liver metastases, often without other systemic disease. Margin-negative (R0) resection of limited metastatic disease, in conjunction with systemic antineoplastic agents, is the primary treatment strategy, leading to long survival times for appropriately selected patients. There is debate over whether the primary tumor and secondaries should be removed at the same time or in a staged manner. Chemotherapy is effective in converting some unresectable liver metastases into resectable disease, with a correspondingly better survival outcome. However, the ideal chemotherapy with or without biological agents and when it should be administered in the course of treatment are uncertain. The role of neoadjuvant chemotherapy in initially resectable liver metastases is controversial. Local delivery of chemotherapy, with and without surgery, can lead to longer disease-free survival times, but it is not routinely used with curative intent. This review focuses on methods to maximize the disease-free survival interval using chemotherapy, surgery, and local methods.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.BREAST.2015.12.007
Abstract: Several complex treatment decisions may be offered to women with early stage breast cancer, about a range of treatments from different modalities including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids can facilitate shared decision-making and improve decision-related outcomes. We aimed to systematically identify, describe and appraise the literature on treatment decision aids for women with early breast cancer, synthesise the data and identify breast cancer decisions that lack a decision aid. A prospectively developed search strategy was applied to MEDLINE, the Cochrane databases, EMBASE, PsycINFO, Web of Science and abstract databases from major conferences. Data were extracted into a pre-piloted form. Quality and risk of bias were measured using Qualsyst criteria. Results were synthesised into narrative format. Thirty-three eligible articles were identified, evaluating 23 in idual treatment decision aids, comprising 13 randomised controlled trial reports, seven non-randomised comparative studies, eight single-arm pre-post studies and five cross-sectional studies. The decisions addressed by these decision aids were: breast conserving surgery versus mastectomy (+/- reconstruction) use of chemotherapy and/or endocrine therapy radiotherapy and fertility preservation. Outcome measures were heterogeneous, precluding meta-analysis. Decisional conflict decreased, and knowledge and satisfaction increased, without any change in anxiety or depression, in most studies. No studies were identified that evaluated decision aids for neoadjuvant systemic therapy, or contralateral prophylactic mastectomy. Decision aids are available and improved decision-related outcomes for many breast cancer treatment decisions including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids for neoadjuvant systemic therapy and contralateral prophylactic mastectomy could not be found, and may be warranted.
Publisher: Harborside Press, LLC
Date: 05-2018
Publisher: Hindawi Limited
Date: 04-11-2015
DOI: 10.1111/TBJ.12537
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/AJCO.12206
Abstract: We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2-positive metastatic breast cancer. We reviewed phase 2 and 3 studies in which an anti-HER2 agent was used in one or both arms of the study. While formal meta-analysis was not possible for such a heterogeneous group of trials, resulting forest plots outline some generalizable findings. There is strong evidence that the addition of an anti-HER2 agent to standard chemo- or endocrine therapy improves clinically relevant measurable outcomes. There is also consistent evidence that initial treatment with trastuzumab alone (and subsequent use of a cytotoxic) is inferior to the initial combination of trastuzumab plus chemotherapy, and that either T-DM1 or dual anti-HER2 agents are superior to single anti-HER2 agent regimens. There is no strong evidence that the use of more than one cytotoxic agent together with an anti-HER2 agent confers any benefit over a single cytotoxic, anti-HER2 combination. This review provides a strong evidence base for current clinical practice with a discussion of treatment in the Australian setting.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2017
DOI: 10.1007/S00520-017-3602-2
Abstract: Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer. Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA). Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1-48.7) weeks in the control group, and 67.6 (95% CI 14.1-98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted. Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/AJCO.12207
Abstract: Improvements in the treatment of metastatic HER2-positive breast cancer constitute one of the great advances in breast cancer medicine of the last generation. From being a highly aggressive fatal condition, the use of anti-HER2-targeted therapies, in particular trastuzumab, has led to significant improvements in disease outcomes. There are reports of increasing numbers of patients alive and well more than 5 years from diagnosis of metastatic disease. Nevertheless, there remain many complex and clinically difficult scenarios where there is little in the way of randomized evidence or published guidelines to guide decision making. As a companion piece to our review of HER2-targeted therapies in the metastatic setting, we decided to focus on a series of clinical scenarios that fell outside of the standard trial-based settings and where opinions and guidance from experienced clinicians and experts in the field would be considered useful to help develop safe and effective treatment strategies. The following eight cases were put forward by our panel of experts, voted on by their peers to select the most relevant and interesting cases, and the discussions worked on by teams of two followed by review and commentary by another team of two.
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA16.00947
Abstract: Patients diagnosed with breast cancer may have supportive care needs for many years after diagnosis. High quality multidisciplinary care can help address these needs and reduce the physical and psychological effects of breast cancer and its treatment. Ovarian suppression and extended endocrine therapy benefits are associated with vasomotor, musculoskeletal, sexual and bone density-related side effects. Aromatase inhibitor musculoskeletal syndrome is a common reason for treatment discontinuation. Treatment strategies include education, exercise, simple analgesia and a change to tamoxifen or another aromatase inhibitor. Chemotherapy-induced alopecia may be a constant reminder of breast cancer to the patient, family, friends, acquaintances and even strangers. Alopecia can be prevented in some patients using scalp-cooling technology applied at the time of chemotherapy infusion. The adverse impact of breast cancer diagnosis and treatment on sexual wellbeing is under-reported. Identification of physical and psychological impacts is needed for implementation of treatment strategies. Fear of cancer recurrence reduces quality of life and increases distress, with subsequent impact on role functioning. Identification and multidisciplinary management are key, with referral to psychosocial services recommended where indicated. The benefits of exercise include reduced fatigue, better mental health and reduced musculoskeletal symptoms, and may also include reduced incidence of breast cancer recurrence. Identification and management of unmet supportive care needs are key aspects of breast cancer care, to maximise quality of life and minimise breast cancer recurrence.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2015
DOI: 10.1007/S00520-015-3001-5
Abstract: Aromatase inhibitor induced musculoskeletal syndrome is experienced by approximately half of women taking aromatase inhibitors, impairing quality of life and leading some to discontinue treatment. Evidence for effective treatments is lacking. We aimed to understand the manifestations and impact of this syndrome in the Australian breast cancer community, and strategies used for its management. A survey invitation was sent to 2390 members of the Breast Cancer Network Australia Review and Survey Group in April 2014. The online questionnaire included 45 questions covering demographics, aromatase inhibitor use, clinical manifestations and risk factors for the aromatase inhibitor musculoskeletal syndrome, reasons for treatment discontinuation and efficacy of interventions used. Aromatase inhibitor induced musculoskeletal syndrome was reported by 302 (82 %) of 370 respondents. Twenty-seven percent had discontinued treatment for any reason and of these, 68 % discontinued because of the musculoskeletal syndrome. Eighty-one percent had used at least one intervention from the following three categories to manage the syndrome: doctor prescribed medications, over-the-counter/complementary medicines or alternative/non-drug therapies. Anti-inflammatories, paracetamol (acetaminophen) and yoga were most successful in relieving symptoms in each of the respective categories. Almost a third of respondents reported that one or more interventions helped prevent aromatase inhibitor discontinuation. However, approximately 20 % of respondents found no intervention effective in any category. We conclude that aromatase inhibitor induced musculoskeletal syndrome is a significant issue for Australian women and is an important reason for treatment discontinuation. Women use a variety of interventions to manage this syndrome however, their efficacy appears limited.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2018
Publisher: Harborside Press, LLC
Date: 2018
Publisher: Hindawi Limited
Date: 14-06-2018
DOI: 10.1111/ECC.12871
Abstract: We examined whether not having been asked by their clinicians about how involved cancer patients would like to be in their treatment decisions is related to discordance between patients' preferred and perceived involvement in treatment decision-making. This was a cross-sectional survey of adult cancer patients recruited from five medical and radiation oncology outpatient clinics in Australia. Discordance of patients' preferred and perceived decision-making roles was assessed via an adapted version of the Control Preferences Scale. Logistic regression modelling was conducted to assess the relationship between role discordance and whether patients were not asked but wanted to be asked about how involved they would like to be in deciding on their treatment. Of 423 study participants, almost a third (n = 128, 31%) reported discordance between their preferred and perceived involvement in their treatment decisions. Of those reporting discordance, 72% (n = 92) were less involved than they would have liked to have been. Not being asked about their preferences for involvement in treatment decisions, despite wanting this, was associated with discordance between patients' preferred and perceived involvement in treatment decision-making (p < 0.04). To achieve patient-centred care, it is vital that clinicians seek patients' views about how involved they would like to be in deciding on their cancer treatment.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2017
DOI: 10.1007/S00520-017-3944-9
Abstract: Cancer patients can be overwhelmed when being confronted with their diagnosis and treatment options. Such information is often provided during one consultation between the patient and treating clinician. In order to achieve optimal cancer care, there may be justification for alternative consultation styles. We assessed, in a s le of adult medical oncology patients, their preferences for (i) attending one 40-min consultation or two 20-min consultations and (ii) receiving written only or both written and online information, when making a cancer treatment decision. This was a cross-sectional survey using a discrete choice design of 159 adult medical oncology patients presenting for their second or subsequent outpatient consultation. Participants were presented with a set of hypothetical scenarios and asked to indicate their most and least preferred scenario. The scenarios contained a caveat explaining that there would be no difference between the available treatment options in terms of when treatment would be initiated and the impact it would have on patients' life expectancy. One hundred forty-seven patients completed the DCE. Of these, 70% (n = 103) preferred being provided with written and online information rather than just written information. This preference was statistically significant (p < 0.01). Fifty-nine percent (n = 86) of patients preferred two 20-min consultations over one 40-min consultation when making a treatment decision. Significantly, more patients preferred two shorter consultations rather than one longer consultation when this was combined with written and online information (p < 0.01). When making a cancer treatment decision, clinicians should consider offering patients written and online information, combined with two shorter consultations.
Publisher: Wiley
Date: 2018
DOI: 10.1111/IMJ.13626
Abstract: The perceptions of those called on to make decisions on behalf of patients who lack capacity at the end of life must accurately reflect patient preferences. To establish the extent to which the views of medical oncology outpatients are understood by their support persons, specifically with regards to (i) preferred type and location of end-of-life care, (ii) preferred level of involvement in end-of-life decision-making and (iii) whether the patient has completed an advance care plan or appointed an enduring guardian. Adults with a confirmed cancer diagnosis and their nominated support persons were approached between September 2015 and January 2016 in the waiting room of an Australian tertiary referral clinic. Consenting participants completed a pen-and-paper survey. Nominated support persons answered the same questions from the patient's perspective. In total, 208 participants (39% of eligible dyads) participated. Observed agreement across the five outcomes ranged from 54% to 84%. Kappa values for concordance between patient-support person responses were fair to moderate (0.24-0.47) for enduring guardian, decision-making, advance care plan and care location outcomes. A slight level of concordance (k = 0.15 95% confidence interval: -0.02, 0.32) was found for the type of care outcome. Relying on support persons' views does not guarantee that patients' actual preferences will be followed. Strategies that make patient preferences known to healthcare providers and support persons while they still have the capacity to do so is a critical next step in improving quality cancer care.
Publisher: Wiley
Date: 07-04-2022
DOI: 10.1002/PON.5921
Abstract: Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI‐SF). We also report on associations between FCR and clinical and demographic characteristics. This is a systematic review and in idual participant data (IPD) meta‐analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI‐SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI‐SF (range 0–36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis. FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185).
Publisher: Wiley
Date: 11-2013
DOI: 10.1111/IMJ.12245
Abstract: Appropriately timed cessation of chemotherapy is an important aspect of good quality palliative care. There is wide variation in the reported rates of chemotherapy administration within the last 30 days of life. To identify predictors of death within 30 days of receiving palliative chemotherapy, and to propose a standard definition by which oncologists and cancer centres can be compared. Patients who received palliative chemotherapy at a regional cancer centre and its rural outreach unit between 2009 and 2011 were included. An adjusted logistic regression model, including all variables, was fit to identify predictors of death within 30 days of receiving palliative chemotherapy. Over a 3-year period, 1131 patients received palliative chemotherapy, 138 (12%) died within 30 days of receiving palliative chemotherapy. Predictors of death within 30 days of palliative chemotherapy were: less than 30 days contact with palliative care (odds ratio 3.30 (95% confidence interval 2.04-5.34), P < 0.001) and male gender (odds ratio 2.02 (95% confidence interval 1.24-3.31), P = 0.0049), but treating clinician, tumour chemoresponsiveness, age, body mass index and survival from initial diagnosis were not. Patients who received chemotherapy in the last 30 days of life were more likely to be male and have a shorter duration of palliative care team involvement. In this study, the observed rate of death within 30 days of chemotherapy is within the range of published data. It is recommended that a standard definition be used to benchmark medical oncology centres and in idual oncologists, and to allow comparison over time.
Publisher: Informa UK Limited
Date: 12-2021
DOI: 10.2147/JMDH.S332972
Publisher: Springer Science and Business Media LLC
Date: 15-03-2016
Publisher: Harborside Press, LLC
Date: 04-2018
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.BREAST.2018.05.009
Abstract: Describe the development, acceptability and feasibility of a Decision Aid (DA) for women with early-stage breast cancer (BC) at average contralateral breast cancer (CBC) risk considering contralateral prophylactic mastectomy (CPM). The DA was developed using the International Patient Decision Aid Standards (IPDAS) and the Ottawa Decision Support Framework. It provides evidence-based information about CPM in a booklet format combining text, graphs and images of surgical options. Twenty-three women with a history of early-stage breast cancer were interviewed in person or over the phone using a 'think aloud approach'. Framework analysis was used to code and analyse data. Twenty-three women participated in the study. Mean age of participants was 58.6 years and time since diagnosis ranged from 14 months to 21 years. Five women had CPM and eighteen had not. Women strongly endorsed the DA. Many felt validated by a section on appearance and found information on average risk of recurrence and metastases helpful, however, noted the importance of discussing personal risk with their surgeon. Many requested more information on surgery details (time taken, recovery) and costs of the different options. The DA was acceptable to women, including the format, content and proposed implementation strategies. Practical and financial issues are important to women in considering treatment options. Women appreciate information about CPM at diagnosis and emphasised the importance of discussing potential downsides of the procedure in addition to benefits. The DA was considered acceptable to facilitate such discussions.
Publisher: Elsevier BV
Date: 05-2016
Abstract: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.
Publisher: Wiley
Date: 25-10-2015
DOI: 10.1111/ANS.13266
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-08-2023
DOI: 10.1200/JCO.23.00126
Abstract: BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93 95% CI, 0.91 to 0.94 adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84 95% CI, 0.63 to 1.12 overweight HR, 1.10 95% CI, 0.82 to 1.49 and obese HR, 0.95 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2019
DOI: 10.1007/S10549-019-05187-Y
Abstract: The separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy. This open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150 mg/m In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity. For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy. Australian Clinical Trials Registry registration number ACTRN12605000478617.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.PEC.2018.12.006
Abstract: Decision aids can improve a number of patient outcomes, but they are not commonly used in clinical practice. This commentary paper provides suggestions for potential next steps of decision aid research, with the aim to facilitate their implementation. We suggest to further standardise clinically meaningful outcomes and outcome measures that should be used to examine the impact of decision aids. Second, using mediation analysis and active control groups could help tease out and explore variables that influence decision aids' effectiveness to help healthcare providers decide when and how to use them in clinical practice. Third, effectiveness trials should be clearly reported and replicated to investigate under what circumstances decision aids work best. Specific checklists for decision aid trials should be used to ensure that all relevant factors are reported in detail. Addressing the above issues will help identify what specific components of decision aids are effective and should be implemented. We can then move towards conducting implementation trials which help increase the use of decision aids in "real-world" healthcare.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-02-2022
DOI: 10.1200/JCO.21.01918
Abstract: The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation in PALLAS. Patients with stage II-III HR+, HER2– disease were randomly assigned to 2 years of palbociclib with adjuvant ET versus ET alone. The primary objective was to compare iDFS between arms. Continuous monitoring of toxicity, dose modifications, and early discontinuation was performed. Association of baseline covariates with time to palbociclib reduction and discontinuation was analyzed with multivariable competing risk models. Landmark and inverse probability weighted per-protocol analyses were performed to assess the impact of drug persistence and exposure on iDFS. Of the 5,743 patient analysis population (2,840 initiating palbociclib), 1,199 (42.2%) stopped palbociclib before 2 years, the majority (772, 27.2%) for adverse effects, most commonly neutropenia and fatigue. Discontinuation of ET did not differ between arms. Discontinuations for non–protocol-defined reasons were greater in the first 3 months of palbociclib, and in the first calendar year of accrual, and declined over time. No significant relationship was seen between longer palbociclib duration or ≥ 70% exposure intensity and improved iDFS. In the weighted per-protocol analysis, no improvement in iDFS was observed in patients receiving palbociclib versus not (hazard ratio 0.89 95% CI, 0.72 to 1.11). Despite observed rates of discontinuation in PALLAS, analyses suggest that the lack of significant iDFS difference between arms was not directly related to inadequate palbociclib exposure. However, the discontinuation rate illustrates the challenge of introducing novel adjuvant treatments, and the need for interventions to improve persistence with oral cancer therapies.
Location: Australia
No related grants have been discovered for Nicholas Zdenkowski.