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Background While therapeutically effective, chemoradiotherapy treatment for high-grade glioma (glioblastoma) is often accompanied by side effects. Exercise has been demonstrated to alleviate the adverse effects of such treatments in other cancers. We aimed to evaluate the feasibility and preliminary efficacy of supervised exercise incorporating autoregulation. Methods Thirty glioblastoma patients were recruited, five declined exercise and 25 were provided with a multimodal exercise intervention for the duration of their chemoradiotherapy treatment. Patient recruitment, retention, adherence to training sessions and safety were evaluated throughout the study. Physical function, body composition, fatigue, sleep quality, and quality of life were evaluated before and after the exercise intervention. Results Eight of the 25 participants commencing exercise withdrew prior to completion of the study (32%). Seventeen patients (68%) demonstrated low to high adherence (33%–100%) and exercise dosage compliance (24%–83%). There were no reported adverse events. Significant improvements were observed for all trained exercises and lower limb muscle strength and function with no significant changes observed for any other physical function, body composition, fatigue, sleep, or quality of life outcomes. Conclusions Only half of glioblastoma patients recruited were willing or able to commence, complete or meet minimum dose compliance for the exercise intervention during chemoradiotherapy indicating the intervention evaluated may not be feasible for part of this patient cohort. For those who were able to complete the exercise program, supervised, autoregulated, multimodal exercise was safe and significantly improved strength and function and may have prevented deterioration in body composition and quality of life.

Objectives Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a real-world setting. Materials and methods Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naive NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety. Results Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2–16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8–17.6) and 13.4 months (95 % CI: 11.8–14.5), respectively, in the overall population and 19.3 months (95 % CI: 15.6–21.8) and 15.9 months (95 % CI: 13.9–19.1) in patients with EGFR exon 19 deletions. Conclusions Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. TRAEs were generally manageable with tolerability-guided dose reductions. Overall, these data independently support findings from randomized controlled trials of afatinib in EGFRm + NSCLC.

Aim: Treatment with pertuzumab-trastuzumab-taxane combinations has become the international standard of care for patients with HER2-positive metastatic breast cancer. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the Australian setting. Method: An expert panel was convened to discuss practical aspects for use of pertuzumab in the Australian clinical setting. The findings of this panel are reported in this article. Results: The combination of pertuzumab-trastuzumab-docetaxel has established efficacy in patients with HER2-positive metastatic breast cancer, prolonging progression-free and overall survival compared to trastuzumab-taxane combinations. In Australia, combinations of pertuzumab and trastuzumab with docetaxel or paclitaxel are reimbursed. Management of treatment related side-effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such as the elderly or those from Asian backgrounds may require particular management strategies. Conclusions: The advent of targeted therapies for women with metastatic HER2-positive breast cancer has markedly improved survival. Combinations of pertuzumab-trastuzumab and a taxane are the standard of care in patients with good performance status. Given prolongation of survival and the importance of quality of life endpoints, the treatment paradigm for patients with metastatic HER2-positive breast cancer is changing rapidly. Careful management of toxicities is required, and dose reduction or switching taxane may be necessary. Further research is required on the efficacy of pertuzumab combinations in patients with brain metastases, and on those who relapse quickly following adjuvant therapy.

Background: An Australian industry-funded decision impact study demonstrated that Oncotype Dx (ODX) changed treatment recommendations (TR) in 24% of hormone receptor+/HER2- patients. ODX is available in Australia, but is self-funded by patients (∼USD 4175), so its use is limited. We sought to evaluate the impact of self-funded ODX on TRs. A high proportion of TR changes would imply a benefit to the broader community if ODX testing were available to all appropriately selected patients. Methods: All Australian physicians who had ordered >5 ODX were invited to participate. Data collected included demographics, tumor characteristics, indication for ODX (confirm need for chemotherapy (CT), confirm omission of CT, or genuine equipoise). Pre- and post Recurrence Score (RS) TRs (CT recommended versus hormone therapy alone (HT)) were also collected. The primary endpoint was the frequency and predictors of TR change. Relationships between categorical variables were assessed using Chi2 test and logistic regression analysis determined factors associated with TR change post-ODX. Results: 382 patients with median age 54 (range 31-76) were included. 18 physicians contributed a median of 17 (5-87) patients. Tumor characteristics were: T1 232 (61%); ≥T2 150 (39%); grade 1 49 (13%), grade 2 252 (66%) and grade 3 79 (21%) and Ki67>15% in 131/231 (49%). 257 (67%) were node negative (N0). Assay indications were: confirm need for CT in 36%, confirm omission of CT in 40% and genuine equipoise in 24%. RS was low in 55%, intermediate in 36% and high in 9%. Of 355 patients with a TR recorded pre-ODX, 38% had TR change post-ODX. 109/168 patients (65%) recommended CT pre-ODX changed to HT alone, and this was more likely if lower grade (82.1% vs 50.8% p15% (27.5% vs 9.8% p=0.015). Overall, TR for CT decreased from 47% to 24%. Influence of adverse prognostic factors (defined as ≥T2, grade 3, ER and/or PR Number of "adverse factors"01234N0 (n=234)Number of patients90116244 RS median (range)16 (0-40)17 (0-41)26 (5-52)31 (22-40) TR change19/90 (21%)45/116 (39%)6/24 (25%)2/4 HT to CT7/71 (10%)10/61 (16%)2/11 (18%)1/2 CT to HT12/19 (63%)35/55 (64%)4/13 (31%)1/2 N+ (n=114)Number of patients22424181 RS median (range)14 (5-34)16 (0-38)14 (0-32)24 (12-50)39 TR change11/22 (50%)21/42 (50%)25/41 (42%)3/8 (38%)0/1 HT to CT3/13 (23%)3/14 (21%)0/12NANA CT to HT8/9 (89%)18/28 (64%)25/29 (86%)3/7 (43%)0/1 Conclusions: Patient self-funded ODX changed TRs in 38%. 65% who would have been recommended CT pre-ODX were spared CT post-ODX, suggesting that traditional histopathological indications for CT in ER+ patients has led to many receiving CT unnecessarily. Where the pre ODX TR was HT alone, only 14% changed to adding CT, suggesting that the indication was reassurance that CT could be omitted. Consideration could be made for third party funding in select patient groups. Citation Format: Chin-Lenn L, Segelov E, De Boer R, Marx G, Hughes TM, McCarthy N, White S, Foo S, Rutovitz J, Della Fiorentina S, Jennens R, Antill Y, Tsoi D, Cronk M, Lombard J, Kiely BE, Chirgwin J, Gorelik A, Mann GB. Indications for, and impact of oncotype DX on adjuvant treatment recommendations when third party funding is unavailable. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-02.

Background: The combination of CDK 4/6 inhibition and endocrine therapy has emerged as the new first line standard of care treatment for patients with hormone receptor (HR) +ve metastatic breast cancer (MBC)1. Ribociclib plus letrozole has been shown to improve PFS (25.3 vs 16.0 months; log-rank P=9.63x10-8) compared to letrozole alone2. More recently, this benefit has also been demonstrated in pre- and peri-menopausal women in combination with ovarian suppression and tamoxifen or an aromatase inhibitor (AI), with an improved overall survival (40.9 months vs OS not reached; HR = 0.712; p=0.00973) in the MONALEESA-7 study3. Approximately 800 patients in Australia participated in the ribociclib medicine access program (MAP) between May 2017 and June 2018, prior to government funding. Beyond eligibility criteria for the program and clinician name, no patient data was initially captured, consistent with usual practice for MAPs, due to the multiple challenges related to ethics, data ownership, security and patient privacy. We have previously demonstrated the feasibility of successful data collection alongside MAPs4 which can yield benefits for clinicians, industry and the broader medical community. Based on this we plan to retrospectively collect data for patients treated as part of the Australian ribociclib MAP. Trial Design: This is a secondary data use, non-interventional study of patients in Australia who received treatment with the combination of an AI and ribociclib, obtained via a MAP, for HR+ HER2- MBC. The target sample size is 250 patients from ~15 sites. De-identified patient data will be retrieved from the patient’s medical records and entered on to an electronic case report form. Data collection is anticipated to commence in July 2019 with the final treatment and survival outcomes collected in late 2020, thus allowing for a minimum of 24 month follow up for all patients from the start date of treatment with ribociclib and AI (May 2017 - June 2018). Study Aims: The primary aim of the study is to describe real world clinical and tumour characteristics of patients with HR+ HER2-ve MBC in Australia who are recommended and received ribociclib in combination with an aromatase inhibitor in the first line setting. Details of adjuvant therapy received and the tolerability of the treatment combination including dose interruptions, dose reductions and significant adverse events of interest related to ribociclib will be assessed. Secondary aims include time to treatment progression and progression free survival for the ribociclib and AI combination, and to explore the disease course post progression, including clinician choice of subsequent lines of therapy in routine clinical practice. References: 1. Cardoso F, Senkus E, Costa A et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol 2018;29:1634-1657. 2. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 2018;29:1541-47. 3. Im SA, Lu YS, Bardia A, et al: Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. June 4, 2019 (early release online) 4. Lok SW, De Boer R, Cordwell C et al. Demonstrating the feasibility of collecting secondary, de-identified data on Australian patients receiving treatment as part of a Medicine Access Program. Intern Med J. 2019 Feb 28. Acknowledgement We thank Novartis for providing funding for this Research Collaboration. Citation Format: Sheau Wen Lok, Sally Baron-Hay, Elgene Lim, Robert Blum, Fran Boyle, Kerrie Clarke, Katharine Cuff, Michael Green, Laeeq Malik, Kelly Mok, Nick Murray, Louise Nott, Michelle Nottage, Ali Tafreshi, Daphne Tsoi, Belinda Yeo, Peter Gibbs, Richard De Boer. A 'real world' experience of CDK4/6 inhibition with ribociclib and endocrine therapy in hormone receptor positive metastatic breast cancer in Australia [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-01.

Background Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion Exercise medicine may positively alter tumour biology through numerous mechanical and non-mechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-3091-8) contains supplementary material, which is available to authorized users.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of bisphosphonates for the prevention of bone loss caused by cancer treatment in women with early breast cancer.

Background. Malignant brain tumors are unpredictable and incurable, with 5-year survival rates less than 30%. The poor prognosis combined with intensive treatment necessitates the inclusion of complementary and supportive therapies that optimize quality of life and reduce treatment-related declines in health. Exercise therapy has been shown to be beneficial in other cancer populations, but no evidence is available for brain cancer survivors. Therefore, we report results from 2 preliminary cases. Methods. Two female patients diagnosed with glioblastoma multiforme and oligodendroglioma participated in a structured and supervised 12-week exercise program. The program consisted of two 1-hour resistance and aerobic exercise sessions per week and additional self-managed aerobic sessions. Outcome measures of strength, cardiovascular fitness, and several psychological indicators (depression, anxiety, and quality of life) were recorded at baseline, after 6 weeks and at the conclusion of the intervention. Results. Exercise was well tolerated; both participants completed all 24 sessions and the home-based component with no adverse effects. Objective outcome measures displayed positive responses relating to reduced morbidity. Similar positive responses were found for psychological outcomes. Scores on the Hospital Anxiety and Depression Scale showed clinically meaningful improvements in depression and total distress. Conclusion. These findings provide initial evidence that, despite the difficulties associated with brain cancer treatment and survivorship, exercise may be safe and beneficial and should be considered in the overall management of patients with brain cancer.

Purpose. A major challenge in treating early-stage hormone receptor (HR)+ breast cancer is selecting women who, after initial surgery, do not require chemotherapy. Better prognostic and predictive tests are needed. The 21-gene assay is the only widely commercially available gene signature that can be performed on formalin-fixed paraffin-embedded tissue. Methods. We conducted a review of the literature supporting the prognostic and predictive ability of the 21-gene assay in HR+ node-negative and node-positive breast cancer patients in chemotherapy-/endocrine-treated and untreated populations. We considered: (a) How accurate is the recurrence score (RS) as a prognostic factor for distant recurrence? (b) How accurate is the RS as a predictive factor for benefit from systemic therapy? (c) How does the RS compare with other prognostic/predictive factors such as tumor size, tumor grade, patient age, and integrated decision aids such as Adjuvant! Online? (d) How do patients and physicians view the 21-gene assay? (e) What are the cost implications of the 21-gene assay? Results. The 21-gene assay: (a) provided accurate risk information; (b) predicted response to cyclophosphamide, methotrexate, and 5-fluorouracil and to cyclophosphamide, doxorubicin, and 5-fluorouracil chemotherapy; (c) added additional information to traditional biomarkers; (d) was viewed positively by both physicians and patients; and (e) fell within the cost-effectiveness values in North America. Conclusion. This assay may be offered to patients with node-negative HR+ breast cancer to assist in adjuvant treatment decisions. Data are accumulating to support the use of the 21-gene assay in HR+ node-positive patients.

Purpose. Most guidelines for hormone receptor (HR)–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. There has been recent incorporation of gene expression analysis in aiding decision making. We evaluated the cost-effectiveness of recurrence score (RS)–guided treatment using 21-gene assay as compared with treatment guided by the Adjuvant! Online program (AOL). Patients and Methods. A Markov model was developed to compare the cost-effectiveness of treatment guided either by 21-gene assay or by AOL in a 50-year-old woman with lymph node–negative HR-positive breast cancer over a lifetime horizon. We assumed that women classified to be at high risk all received chemotherapy followed by tamoxifen and those classified to be at low risk received tamoxifen only. The model took a health care payer's perspective with results reported in 2008 Canadian dollars ($). Event rates, costs, and utilities were derived from the literature. Both costs and benefits were discounted at 5%. Outcome measures were life years gained, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Results. For a 50-year-old woman, RS-guided treatment was associated with an incremental lifetime cost of $4,102 and a gain in 0.065 QALY, with an ICER of $63,064 per QALY compared with AOL-guided treatment. ICER increased with increasing cost of 21-gene assay and increasing age of patients. Results were most sensitive to probabilities relating to risk categorization and recurrence rate. Conclusions. The 21-gene assay appears cost-effective from a Canadian health care perspective.