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The US Food and Drug Administration today granted accelerated approval to atezolizumab (Tecentriq, Genentech/Roche) plus the chemotherapy nab-paclitaxel (Abraxane, Celgene) for the first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC).

Atezolizumab is the first immunotherapy to be approved for breast cancer.

The approval is based on progression-free survival results and continued approval may be contingent upon confirmatory trial data.

The new approval of the combination is based on safety and efficacy results from the multicenter IMpassion130 trial, which were presented at the European Society for Medical Oncology (ESMO) 2018 Congress and simultaneously published in the New England Journal of Medicine.

The trial randomly assigned 451 patients with locally advanced or metastatic triple-negative breast cancer patients to atezolizumab and 451 to placebo. All 902 patients also received nab-paclitaxel.

In this intention-to-treat (ITT) population, atezolizumab significantly reduced the risk of disease progression or death (progression-free survival; PFS) compared with placebo (median PFS = 7.2 vs. 5.5 months; hazard ratio [HR] = 0.80, 95% confidence interval [CI], 0.69 – 0.92, P = .0025).

Atezolizumab also improved median overall survival (OS), but statistical significance was not met at the time of the interim analysis (21.3 vs. 17.6 months; HR = 0.84, 95% CI, 0.69 – 1.02, P = .0840).

These co-primary endpoints were investigator assessed; median follow-up was 12.9 months.

The trialists also performed a subgroup analysis among patients who were PD-L1+, defined as expression ≥ 1% on tumor-infiltrating immune cells. In this analysis, the atezolizumab group consisted of 185 patients and the placebo group 184 patients.

In this PD-L1+ population, atezolizumab significantly reduced the risk of disease progression or death (median PFS = 7.5 vs. 5.0 months; HR = 0.62, 95% CI, 0.49 – 0.78, P < .0001). The immunotherapy also improved median OS (25.0 vs. 15.5 months; HR = 0.62, 95% CI, 0.45 – 0.86).

Presenting these results last year, lead study author Peter Schmid, MD, PhD, St. Bartholomew’s Breast Cancer Centre, Barts Health NHS Trust, London, United Kingdom, said that, in the PD-L1+ subgroup, “we see a nearly 10-month overall survival difference, which I think is a key encouragement to see this drug as a new standard.”

However, Kathy Miller, MD, of the IU Simon Cancer Center at Indiana University, Indianapolis, was uncertain about that conclusion because the OS findings were not final. In a Medscape commentary about this trial, she said: “The authors of IMpassion130 conclude that atezolizumab plus nab-paclitaxel is a new standard of care in the PD-L1-positive subgroup. At this point, I have to say I disagree. What they’ve reported so far is a very modest improvement in progression-free survival. We honestly don’t yet know whether there is an improvement in overall survival.”

In the pivotal trial, atezolizumab was administered at a fixed dose of 840 mg via intravenous (IV) infusion on days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity. Nab-paclitaxel was administered at a starting dose of 100 mg/m2 via IV infusion on days 1, 8, and 15 of each 28-day cycle. 

The median duration of atezolizumab and nab-paclitaxel treatment in the atezolizumab group was 24.1 weeks and 22.1 weeks, respectively, and the median duration of placebo and nab-paclitaxel in the placebo group was 22.1 weeks and 21.8 weeks, respectively.

Over the study period, 358 (79.4%) patients in the atezolizumab group and 378 (83.8%) of those in the placebo group had disease progression or died.

The investigators reported that adverse events (AEs) were consistent with the safety profiles of the study drugs; no new safety signals were identified with the combination of atezolizumab plus nab-paclitaxel.

Severe adverse events (SAEs) were reported in 23% of the atezolizumab group vs 18% of the placebo group.

Grade 3-4 AEs occurred in 49% of the atezolizumab group vs 42% of the placebo group. The most common were neutropenia (8%); peripheral neuropathy (6%); decreased neutrophil count (5%); fatigue (4%); and anemia (3%).

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