OS Benefit of Adding Atezolizumab to Nab-Paclitaxel for Patients With Advanced, PD-L1–Positive Triple-Negative Breast Cancer

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.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

1. 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.
2. 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.
3. 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.