Atezolizumab plus nab-paclitaxel prolongs OS in PD-L1 IC–positive triple-negative breast cancer

A combined regimen of atezolizumab and nanoparticle albumin-bound (nab)-paclitaxel (A+nP) improves overall survival (OS) vs placebo plus nab-paclitaxel (P+nP) in patients with previously untreated, inoperable, locally advanced or metastatic, PD-L1 immune cell (IC)–positive triple-negative breast cancer (TNBC), according to the final analysis of the IMpassion130 study.

“Our study’s findings support a positive benefit-risk profile for A+nP as first-line treatment in patients with PD-L1 IC–positive metastatic TNBC,” said Professor Leisha Emens of the University of Pittsburgh, Pennsylvania, US.

The final analysis, reported after a median follow-up of 19.7 months in the A+nP group and 18.0 months in the P+nP group, showed a numerical improvement of OS (median, 21.0 months vs 18.7 months; hazard ratio [HR], 0.87; 95 percent confidence interval [Cl], 0.75 to 1.02; p=0.077) with A+nP vs P+nP in the intention-to-treat (ITT) population. [Emens LA, et al, ESMO 2020, abstract LBA16]

A clinically meaningful OS improvement was demonstrated with A+nP vs P+nP (median, 25.4 months vs 17.9 months; HR, 0.67; 95 percent CI, 0.53 to 0.86) in PD-L1 IC–positive patients, who accounted for 41 percent of the overall trial population. In these patients, 3-year OS rates were 36 percent for A+nP and 22 percent for P+nP.

“The OS results in the PD-L1 IC–positive population were consistent with the first and second interim analyses [first interim analysis: HR, 0.62; 95 percent CI, 0.45 to 0.86] [second interim analysis: HR, 0.71; 95 percent CI, 0.54 to 0.93],” said Emens.

Across other subgroups of patients in the ITT population, the OS difference with A+nP vs P+nP was similar and did not reach statistical significance. In patients with PD-L1 IC–negative disease, A+nP did not demonstrate a significant OS benefit vs P+nP (HR, 1.02; 95 percent CI, 0.84 to 1.24).

In the multicentre, randomized, phase III IMpassion130 study, 902 patients with previously untreated, locally advanced or metastatic TNBC and Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 who had received no previous chemotherapy were randomized (1:1) to receive A+nP or P+nP. Atezolizumab 840 mg or placebo was administered intravenously on days 1 and 15, while nab-paclitaxel was administered intravenously at a dose of 100 mg/m² of body surface area on days 1, 8 and 15, of every 28-day cycle.

Patient characteristics were well-balanced between the A+nP and P+nP groups at baseline, with 51 percent of patients in both treatment groups having prior taxane exposure.

The safety profile of A+nP was consistent with those of individual treatment components, with no safety signals identified during additional follow-up. Rates of all-grade adverse events (AEs) (99 percent for A+nP vs 98 percent for P+nP) and grade 3/4 AEs (51 percent vs 43 percent) were comparable between the A+nP and P+nP groups. Alopecia (57 percent for A+nP vs 57 percent for P+nP), fatigue (47 percent vs 45 percent) and nausea (47 percent vs 38 percent) were the most common AEs.

Rates of all-grade AEs of special interests (AESIs), such as rash (36 percent vs 26 percent), hypothyroidism (18 percent vs 4 percent) and hyperthyroidism (5 percent vs 1 percent), were higher with A+nP vs P+nP. “Nonetheless, most of these events were of low grade and can be well managed,” Emens noted.