The 2018 European Society for Medical Oncology (ESMO) Congress was held from October 19 to 23 in Munich, Germany. Nearly 28,000 participants, including oncology professionals, patient advocates, and industry representatives, attended from around the world to hear the most recent updates in oncology, focusing on innovation, integration, and sustainability of cancer care. Over the next weeks, prIME LINES will highlight results of key trials that have the potential to impact clinical practice.
During the first Presidential Symposium, Peter Schmid, MD, PhD (Bart’s Cancer Institute, London), presented results from the interim analysis of the IMpassion130 trial (N = 902), a global, double-blind, randomized phase III trial comparing the combination of the PD-L1 inhibitor atezolizumab plus nab-paclitaxel to nab-paclitaxel plus placebo in patients with locally advanced or metastatic triple-negative breast cancer (TNBC). Results from this study were simultaneously published in The New England Journal of Medicine.
The trial met its co-primary endpoint of improved progression-free survival (PFS) in both the intent-to-treat (ITT) and PD-L1-positive populations. At a median follow-up of 12.9 months, the median PFS for patients receiving atezolizumab plus nab-paclitaxel was 7.2 months, compared to 5.5 months for patients receiving nab-paclitaxel plus placebo (HR 0.80, P = .0025). The PFS benefit with atezolizumab was consistent across all prespecified patient subgroups. For PD-L1-positive patients, the median PFS was 7.5 months with atezolizumab and 5.0 months with placebo (HR 0.62, P<.0001). While overall survival (OS) data are not yet mature, there was a trend in the ITT population toward improved OS in patients treated with atezolizumab plus nab-paclitaxel (21.3 months vs 17.6 months; HR 0.84, P = .084). The impact of atezolizumab on OS was more pronounced in the PD-L1-positive patient population, where there was a 9.5-month improvement in OS (25.0 months vs 15.5 months; HR 0.62). The overall response rate (ORR) was higher in the atezolizumab plus nab-paclitaxel arm in both the ITT population (56% vs 46%) and in PD-L1-positive patients (59% vs 43%).
The combination of atezolizumab and nab-paclitaxel was associated with a manageable toxicity profile. Treatment-related grade 3/4 adverse events (AEs) occurred in 40% of patients receiving atezolizumab plus nab-paclitaxel and 30% of patients receiving nab-paclitaxel plus placebo. The most common AEs were generally similar between arms, with neutropenia, decreased neutrophil count, peripheral neuropathy, fatigue, and anemia as the most common grade 3/4 AEs. Immune-related AEs occurred at a low rate and were generally of grade 1 or 2. Of note, patients receiving atezolizumab were able to receive the full dose of nab-paclitaxel.
Dr Schmid concluded that the addition of atezolizumab to nab-paclitaxel results in a clinically meaningful improvement in PFS and a trend toward improved OS with manageable toxicity, supporting this combination as a new treatment option for newly diagnosed patients with advanced PD-L1-positive TNBC. In his discussion, Giuseppe Curigliano, MD, PhD (University of Milan, Italy), highlighted this to be the first positive trial of immunotherapy in TNBC and the first trial to bring breast cancer into the immunotherapy area, and agreed that atezolizuamb plus nab-paclitaxel is a new standard of care for PD-L1-positive TNBC.