Highlights from the ASCO 2015 Annual Meeting

Intro text: 


The American Society of Clinical Oncology (ASCO) Annual Meeting 2015 took place recently in Chicago, USA. With approximately 30,000 oncologists and other scientists involved in the care of patients with cancer and/or cancer research, the ASCO Annual Meeting provided the results of important clinical trials with impact on the field of breast cancer oncology, which are summarized below.


Dr Arlene Chan, MD, of the Breast Cancer Research Centre at Western Australia and Curtin University, Australia, presented results of the ExteNET study. This was a phase III study that randomized 2,840 women with HER2-positive breast cancer and prior adjuvant trastuzumab and chemotherapy to receive either 240 mg/day of neratinib for 1 year or placebo (1,420 patients in each arm). Neratinib is a small molecule inhibitor that targets 3 proteins with oncogenic signalling properties, namely HER1, HER2, and HER4.  The primary endpoint was of the trial was invasive disease-free survival (iDFS). At 24 months, patients who received neratinib had an iDFS rate of 93.9% compared to 91.6% in the placebo group (hazard ratio [HR] 0.67, 95% CI [0.50, 0.91]; p = 0.009). No data were presented concerning overall survival, since there was a short follow-up period of the ExteNET study.


Another trial focusing on patients with HER2-positive breast cancer, the MARIANNE trial, was reported by Dr Paul Anthony Ellis, MD, FRACP, of Guy’s Hospital and the Sarah Cannon Research Institute, United Kingdom. The MARIANNE trial randomly assigned 1,095 patients with progressed or recurrent locally advanced or previously untreated metastatic HER2-positive breast cancer to receive T-DM1 plus pertuzumab (363 patients), T-DM1 plus placebo (367 patients), or HT (trastuzumab plus docetaxel or paclitaxel; 365 patients), having progression free survival (PFS) as primary endpoint. After a median follow-up of 35 months, the study did not reach its primary endpoint, since both T-DM1–containing regimens showed noninferior PFS, but not superiority, over the trastuzumab-containing arm. The median PFS was 15.2 months in the T-DM1 plus pertuzumab arm (HR 0.87, 95% CI [0.69, 1.08]; p = 0.14), 14.1 months with T-DM1 alone (HR 0.91, 95% CI [0.73, 1.13]; p = 0.31) compared with 13.7 months with HT. The overall survival data were not yet reached. Based on the results of the MARIANNE and the earlier reported results of the CLEOPATRA trial, currently the triplet of trastuzumab/pertuzumab/taxane should be considered as the preferred regimen for first line systemic treatment of metastatic HER2-positive breast cancer.


Dr Richard G. Margolese, MD, CM, of the Jewish General Hospital and McGill University, Canada, presented the results of the NRG Oncology/NSABP B-35 study that focused on theendocrine treatment of patients with ductal carcinoma in situ (DCIS). In particular, this study randomly assigned 3,104 patients to receive 20 mg per day of tamoxifen plus placebo or 1 mg per day of anastrozole plus placebo for 5 years, with all patients having received breast radiotherapy. The primary endpoint was breast cancer–free interval (BCFI). Interestingly, it was reported that there was no difference in BCFI between the two treatment groups until about 96 months of follow-up. At 10 years, 93.5% of women in the anastrozole group and 89.2% in the tamoxifen group remained free of disease (HR 0.73; p = 0.03). An interesting finding of this trial was the impact of age on the clinical outcome of women with DCIS treated with anastrozole or tamoxifen. In particular, although there was no difference in disease-free survival in the overall population (82.7% with anastrozole vs. 77.9% with tamoxifen; HR 0.89; p = 0.21), among women with age 60 or less, anastrozole was associated with a significant benefit: 88.8% remained disease-free compared with 81.5% of those who received tamoxifen (HR 0.69; p = 0.02). In contrast, the corresponding values among women older than 60 years old were 77.3% and 74.8% in the anastrozole and tamoxifen arms, respectively (HR 1.03; p = 0.79). Similar findings were reported for other secondary efficacy endpoints of the trial, establishing a certain pattern of increased efficacy of anastrozole over tamoxifen among younger women with DCIS.


A trial addressing the issue of endocrine resistance in the metastatic setting of luminal breast cancer was reported by Prof. Nicholas Turner of the Royal Marsden Hospital, London, UK. PALOMA3 is a double-blind phase III study, that randomized 521 women with hormone receptor-positive/HER2-negative metastatic breast cancer, whose disease had relapsed or progressed on prior endocrine therapy, in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant respectively, having PFS as primary endpoint. At the time of the interim analysis the study met its primary endpoint, since the median PFS was 9.2 months for palbociclib plus fulvestrant and 3.8 months for placebo plus fulvestrant (HR 0.422, p < 0.000001). Of note, consistent benefit from the addition of palbociclib was seen in both pre- and post-menopausal women. Concerning the toxicity profile, the most common adverse effects in the palbociclib plus fulvestrant vs placebo plus fulvestrant arms were neutropenia (78.8% vs 3.5%), leucopenia (45.5% vs 4.1%), and fatigue (38.0% vs 26.7%). Very low rates of febrile neutropenia were reported across the study population (0.6% patients on palbociclib plus fulvestrant and 0.6% patients on placebo plus fulvestrant). The discontinuation rate due to adverse events was 2.0% on palbociclib and 1.7% on placebo, further demonstrating an overall good tolerability of the investigational agent palbociclib.