|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
According to results presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, a second interim analysis of overall survival (OS) for patients with advanced triple-negative breast cancer (TNBC) enrolled in a large phase 3 clinical trial evaluating atezolizumab versus placebo, both in combination with chemotherapy, showed immune checkpoint inhibitor therapy significantly prolonged OS in the subgroup of patients with tumors expressing programmed cell death-ligand 1 (PD-L1).
The randomized, placebo-controlled, double-blind IMpassion130 trial (ClinicalTrials.gov Identifier: NCT02425891) randomly assigned (in a 1:1 ratio) 902 patients with advanced, inoperable TNBC who had not received prior treatment with systemic therapy for advanced disease to get treatment with nab-paclitaxel plus the PD-L1 inhibitor, atezolizumab (451 individuals), or nab-paclitaxel plus placebo (451 individuals). Coprimary end points of the study were progression-free survival (PFS), PFS in patients with detectable tumor levels of PD-L1, OS, and OS in patients with detectable PD-L1.
The previously reported primary PFS analysis of the trial, performed at a median follow-up of 12.9 months, showed a significant improvement in median PFS for patients in the intention-to-treat (ITT) population receiving atezolizumab (ie, 7.2 months vs 5.5 months; hazard ratio [HR], 0.80; 95% CI, 0.69- 0.92; P =.002).
At that time, median OS in the ITT population was reported as 21.3 months and 17.6 in the atezolizumab and placebo arms, respectively. (HR, 0.84; 95% CI, 0.69-1.02; P =.08).2 However, significant differences between the 2 treatment arms with respect to both PFS and OS, favoring atezolizumab, were observed in the subgroup of patients with detectable tumor levels of PD-L1.
Reported at ASCO 2019 were the results of the second interim OS analysis of this study. While the OS difference between the 2 study arms for the ITT population was still not significant (21.0 months vs 18.7 months, in favor of atezolizumab; HR, 0.86; 95% CI, 0.72-1.02; P =.0777), median OS was 25.0 months vs 18.0 months (HR, 0.71; 95% CI, 0.54-0.93) in the population with tumor PD-L1 levels of 1% or higher (369 individuals). Respective rates of 2-year OS in the atezolizumab and placebo arms were 42% and 39% in the ITT population, and 51% and 37% in the subgroup with detectable tumor PD-L1 levels.
Results of an updated safety analysis of this study were also presented at ASCO 2019,3 and were consistent with those previously reported, which showed that the atezolizumab regimen was tolerable; no new, or late-onset toxicities were reported with this treatment.2 Of note, frequencies of the following any-grade adverse events were higher in patients in the atezolizumab/nab-paclitaxel arm compared with those receiving placebo/nab-paclitaxel: rash (34% vs 26%), hypothyroidism (18% vs 5%), hyperthyroidism (5% vs 1%), and pneumonitis (4% vs <1%).3
Peter Schmid, MD, PhD, Barts Cancer Institute, Queen Mary University, London, U.K., who presented these results, concluded his presentation by stating that “IMpassion130 is the first and only phase 3 study to show a clinically meaningful benefit of first-line immunotherapy in metastatic triple-negative breast cancer.”
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- Schmid P, Adams S, Rugo HS, et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo) + nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 1003.
- Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108-2121.
- Schneeweiss, Hope S. Rugo, Eric P. Winer, et al. IMpassion130: Expanded safety analysis from a P3 study of atezolizumab (A) + nab-paclitaxel (nP) in patients (pts) with treatment (tx)-naïve, locally advanced or metastatic triple-negative breast cancer (mTNBC). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 1068.