Rachel F Dear

Chemotherapy in metastatic breast cancer: A summary of all randomised trials reported 2000-2007.

AIM To summarise the findings of all randomised trials comparing chemotherapy regimens for metastatic breast cancer that were reported between 2000 and 2007 inclusive. METHODS We searched the specialised register of clinical trials maintained by the secretariat of the Cochrane Breast Cancer Group (CBCG) from 2000 to 2007, and abstracts from the American Society of Clinical Oncology (ASCO) annual scientific meeting (2000-2007). RESULTS Eighty reports of 63 trials were identified as eligible for this review. Whilst over 30% of the trials reported a statistically significant difference in response rate or progression free survival, only 8 trials (13%) reported a difference in overall survival. Thirty percent reported quality of life data. Very few trials examined the critical clinical questions of duration and the relative merits of combination versus sequential single agent chemotherapy. CONCLUDING STATEMENT There is little evidence from trials reported from 2000 to 2007 that major survival differences exist between many commonly employed chemotherapy regimens.

Pulmonary metastasectomy for bone and soft tissue sarcoma in Australia: 114 patients from 1978 to 2008.

Aims:  The aim of this study is to analyze the prognostic factors for overall and relapse‐free survival that may help select patients for pulmonary metastasectomy and inform their prognosis.

Exploring the communication of oncologists, patients and family members in cancer consultations: development and application of a coding system capturing family-relevant behaviours (KINcode).

Family members (FMs) regularly attend oncology consultations. However, limited studies have assessed actual behaviours of oncologists, patients and FMs – particularly during decision‐making. The current study aimed the following: (i) to rigorously develop a family (kin) interaction coding system (KINcode) capturing communication and decision‐making behaviours of FMs and family‐relevant behaviours of oncologists and patients and (ii) to apply KINcode to initial oncology consultations.

Consumer input into research: the Australian Cancer Trials website

BackgroundThe Australian Cancer Trials website (ACTO) was publicly launched in 2010 to help people search for cancer clinical trials recruiting in Australia, provide information about clinical trials and assist with doctor-patient communication about trials. We describe consumer involvement in the design and development of ACTO and report our preliminary patient evaluation of the website.MethodsConsumers, led by Cancer Voices NSW, provided the impetus to develop the website. Consumer representative groups were consulted by the research team during the design and development of ACTO which combines a search engine, trial details, general information about trial participation and question prompt lists. Website use was analysed. A patient evaluation questionnaire was completed at one hospital, one week after exposure to the website.ResultsACTOs main features and content reflect consumer input. In February 2011, it covered 1, 042 cancer trials. Since ACTOs public launch in November 2010, until the end of February 2011, the website has had 2, 549 new visits and generated 17, 833 page views. In a sub-study of 47 patient users, 89% found the website helpful for learning about clinical trials and all respondents thought patients should have access to ACTO.ConclusionsThe development of ACTO is an example of consumers working with doctors, researchers and policy makers to improve the information available to people whose lives are affected by cancer and to help them participate in their treatment decisions, including consideration of clinical trial enrolment. Consumer input has ensured that the website is informative, targets consumer priorities and is user-friendly. ACTO serves as a model for other health conditions.

Identifying and prioritising gaps in colorectal cancer trials research in Australia

Objectives: To identify gaps in colorectal cancer clinical trials research in Australia and to suggest and prioritise trials to fill those gaps.

Recurrent ovarian cancer: treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experience.

Aim:  To describe the overall survival, progression‐free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer.

Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers

Background Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. Purpose An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. Methods The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. Results The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers’ information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Limitations Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data. Conclusion Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

Barriers and enablers to implementing scalp cooling in Australia: a qualitative study of health professionals’ attitudes to and experience with scalp cooling

BackgroundChemotherapy-induced alopecia is a common and distressing adverse event for patients. Scalp cooling to reduce this alopecia has been available in Europe for more than a decade, but only recently introduced in Australia. The aim of this study was to qualitatively explore health professionals’ perceptions of the barriers and enablers to the implementation of scalp cooling in Australian cancer centres.MethodsUsing a qualitative methodology, telephone interviews were conducted with 21 health professionals working in a tumour stream where chemotherapy-induced alopecia is an adverse event of treatment. Participants were recruited from five centres in Australia where scalp cooling is currently available and one centre without access to the technology.ResultsFour interrelated themes were identified: (1) health professional attitudes, (2) concerns for patient equity, (3) logistical considerations and (4) organisational support.ConclusionsThis qualitative study provides the first methodological exploration of Australian health professionals’ perceptions of barriers and enablers to scalp cooling uptake. The results highlighted health professional support drives the introduction of scalp cooling. Integration of the technology requires adjustments to nursing practice to manage the increased time, workload and change in patient flow. Strategies to manage the change in practice and organisational support for change in work flow are essential for successful implementation into routine care.

Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach

BackgroundMultidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments.MethodsWe analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines.ResultsMachine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p < 0.01, representing 43% and 53% variations from ESMO/NCCN guidelines, respectively). Using ten-fold cross-validation, the best classifiers achieved areas under the receiver operating characteristic curve (AUC) of 0.940 for chemotherapy (95% C.I., 0.922—0.958), 0.899 for the endocrine therapy (95% C.I., 0.880—0.918), and 0.977 for trastuzumab therapy (95% C.I., 0.955—0.999) respectively. Overall, bootstrap aggregated classifiers performed better among all evaluated machine learning models.ConclusionsA machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

Abstract A084: DENALI: a 3-arm double-blind randomized phase 2 study of carboplatin, pemetrexed, and placebo (CPP) versus carboplatin, pemetrexed, and either 1 or 2 truncated courses of demcizumab (CPD) in patients with non-squamous non-small cell lung cancer (NSCLC)

Introduction: Delta-like ligand 4 (DLL4) is a ligand that activates the Notch pathway, which is important for cancer stem cell (CSC) survival. Demcizumab is a humanized, anti-DLL4 antibody that has been shown using an in vivo tumorigenicity limiting dilution assay to inhibit tumor growth and decrease CSC frequency in minimally passaged human xenograft models. In addition, inhibition of DLL4 has also been shown in preclinical studies to cause dysfunctional sprouting of new vessels, resulting in an antiangiogenic effect. Data from a phase 1b study of carboplatin (C), pemetrexed (P), and demcizumab (D) in patients with 1st-line metastatic non-squamous NSCLC led to this double-blind randomized 3-arm placebo (Pl)-controlled phase 2 study. Methods: Patients with non-squamous NSCLC were randomized (1:1:1) to 1st-line therapy with either Arm 1 -CPPl, Arm 2 -CPD with a single 70-day truncated course of demcizumab or Arm 3 - CPD with two 70-day truncated courses of demcizumab (second course starting on Day 168). CP were given at usual dose and schedule; P/D was given IV on days 1 and 15 in cycles 1-3 and 7-9. The primary endpoint was response rate and secondary endpoints included progression-free survival, survival, safety, immunogenicity, pharmacokinetics, and biomarkers of Notch signaling and CSCs in blood, hair follicles, and tumor cells. The primary study analyses compared CPPl to the two pooled CPD arms. Results: 82 patients were randomized and all 82 were treated. The median age was 61, the male/female ratio was 40/42, 80 pts had adenocarcinoma, 0 pts harbored EGFR mutation or ALK rearrangement, and 15 were KRAS mutated. The response/clinical benefit rates were 52%/92% and 28%/79% in the CPPl and pooled CPD arms, respectively (response p value = 0.04). The median progression-free survival (PFS) was 8.7 months (95% CI: 5.4-12.5) in the CPPl arm and 5.5 months (95% CI: 4.1-6.9) in the pooled CPD arms (HR = 2.3; 95%CI: 1.1-4.8). The interim median overall survival (OS) for the CPPl and pooled CPD arms was not reached (95% CI: 16.0—NR) and 15.5 months (95% CI: 8.3-NR) (HR= 2.4; 95% CI: 0.94-6.1), respectively. CPD was generally well tolerated with nausea, fatigue, constipation, anemia, and hypertension being the most common reported toxicities. The incidences of the Grade 3 or greater toxicities of special interest with demcizumab therapy were hypertension (8% vs 25%), pulmonary hypertension (0% vs 0%), heart failure (0% vs. 0%), and bleeding (0% vs. 3.4%) in the CPPl and pooled CPD arms, respectively. Conclusions: The addition of either 1 or 2 truncated courses of demcizumab to 1st-line carboplatin and pemetrexed did not improve the efficacy compared to CPPl in patients with 1st-line metastatic NSCLC. CPD therapy was generally well tolerated. Citation Format: Brett Hughes, Andrew Dean, Ben Markman, Luke Dreisbach, Mariano Provencio, Libero Ciuffreda, Rachel Dear, Peter Graze, Alforia Nadal, Baerin Houghton, Teresa Moran, Rachel Roberts, Grace Dy, Taus Alvaro, Alex Martinez Marti, Rainer Brachmann, Robert Stagg, Ramaswamy Govindan. DENALI: a 3-arm double-blind randomized phase 2 study of carboplatin, pemetrexed, and placebo (CPP) versus carboplatin, pemetrexed, and either 1 or 2 truncated courses of demcizumab (CPD) in patients with non-squamous non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A084.