Addition of Atezolizumab to Chemotherapy Did Not Improve Overall Survival Among Patients With Early Relapsing Unresectable Advanced Triple-Negative Breast Cancer

According to results from the phase 3 IMpassion132 study, the addition of atezolizumab to chemotherapy did not improve overall survival (OS) among patients with early relapsing unresectable advanced or metastatic triple-negative breast cancer (TNBC).

“Among patients who develop metastatic TNBC following (neo)adjuvant anthracycline and/or taxane chemotherapy, approximately half of them experience relapse within 12 months of completing chemotherapy,” stated Rebecca Dent, MD, National Cancer Center Singapore, Singapore, and coauthors. “Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce.”

In this international, placebo-controlled trial, 354 patients who experienced disease recurrence < 12 months after curative treatment were enrolled. Patients were required to have received anthracycline- and taxane-containing neoadjuvant or adjuvant chemotherapy for early disease and were not allowed to have received chemotherapy or systemic targeted therapy for advanced TNBC. Initially patients were enrolled irrespective of PD-L1 status, however enrollment was eventually restricted to PD-L1–positive patients. Enrolled patients were randomized on a 1-to-1 basis to receive either placebo or 1200 mg of atezolizumab every 21 days, plus investigator’s choice chemotherapy until disease progression or unacceptable toxicity. Stratification was based on chemotherapy regimen, visceral metastases, and initial PD-L1 status. The primary end point was OS in the PD-L1–positive population and in the modified intention-to-treat population (mITT). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.

At the data cutoff point, in the PD-L1–positive population, the median OS was 11.2 months in the placebo arm and 12.1 months in the atezolizumab arm (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.73 to 1.20; P = .59). As the primary objective in the PD-L1–positive population was not met, OS was not formally tested in the mITT population and prespecified secondary end points were not formally tested in either patient population. 

In the PD-L1–positive population, 269 patients experienced treatment-related adverse events in the placebo arm compared to 265 patients in the atezolizumab arm. In the mITT population, treatment-related adverse events were experienced by 158 patients in both treatment arms. Across all study populations, 80% of patients discontinued treatment due to disease progression, 3% of patients discontinued due to symptomatic deterioration, and 3% of patients died. The most common adverse events included anemia, nausea, neutropenia, alanine transaminase increase, and aspartate aminotransferase increase. 

“Patients with TNBC and early relapse continue to represent a treatment conundrum and unfortunately results from the IMpassion132 trial do not show improved outcomes with the addition of a PD-L1 inhibitor,” concluded Dr Dent et al. “A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.” 

Source: 

Dent R, Andre F, Goncalves A, et al. IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Ann Oncol. Published online: May 15, 2024. doi: 10.1016/j.annonc.2024.04.001