Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer

Takeaway

• In patients with metastatic triple-negative breast cancer (BCa), first-line atezolizumab with nab-paclitaxel was associated with significantly longer progression-free survival (PFS) vs nab-paclitaxel alone in the intention-to-treat and PD-L1-positive cohorts.

Why this matters

• In triple-negative BCa, the expression of PD-L1 occurs mainly on tumour-infiltrating immune cells rather than on tumour cells and can inhibit anticancer immune responses.
• The safety and activity of atezolizumab with nab-paclitaxel in triple-negative BCa have been shown in a phase 1b study.
• IMpassion130 is an international phase 3 trial of first-line atezolizumab plus nab-paclitaxel in locally advanced or metastatic triple-negative BCa.

Results

• Each group included 451 patients (median follow-up: 12.9 months).
• In the intention-to-treat analysis, overall median PFS was 7.2 months with atezolizumab plus nab-paclitaxel vs 5.5 months with placebo plus nab-paclitaxel (HR for progression or death 0.80; 95% CI 0.69-0.92; P=0.002).
• In patients with PD-L1-positive tumours, median PFS was 7.5 months and 5.0 months, respectively (HR 0.62; 95% CI 0.49-0.78; P<0.001).
• In the intention-to-treat analysis, median overall survival (OS) was 21.3 months vs 17.6 months (HR for death, 0.84; 95% CI 0.69-1.02; P=0.08).
• Formal testing of OS in the PD-L1-positive subgroup was not conducted at this interim analysis but Kaplan-Meier analyses showed median overall survival (OS) of 25.0 months vs 15.5 months (hazard ratio 0.62; 95% CI 0.45-0.86).
• Adverse events leading to discontinuation of any agent occurred in 15.9% vs 8.2%.

Study design

• Phase 3 randomised, double-blind, placebo-controlled IMpassion130 trial (NCT02425891) of first-line atezolizumab plus nab-paclitaxel vs placebo plus nab-paclitaxel in patients with locally advanced or metastatic triple-negative BCa.
• Funding: F. Hoffmann-La Roche/Genentech

Limitations

• Boundary for declaring a statistical advantage for atezolizumab plus nab-paclitaxel in the intention-to-treat population was not crossed.
• Formal testing was not performed in the PD-L1-positive subgroup.