The addition of atezolizumab to carboplatin chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (TNBC) regardless of PD-L1 status, according to phase 2 study results published in JAMA Oncology.

Researchers also identified factors associated with favorable OS and PFS outcomes in patients treated with atezolizumab plus carboplatin, including higher levels of tumor-infiltrating lymphocytes and tumor mutational burden, obesity, and elevated blood glucose levels. Because high PD-L1 expression has been observed in patients with TNBC, a rationale exists for including immune checkpoint inhibition as part of the standard treatment platform. However, a phase 3 study evaluating the monoclonal antibody atezolizumab versus paclitaxel did not record a significant improvement in PFS or OS when given as monotherapy.

Jennifer Pietenpol, PhD, professor of cancer research, professor of biochemistry and otolaryngology, and chief scientific strategy officer and EVP of research at Vanderbilt University Medical Center, and colleagues conducted the randomized TBCRC 043 trial to determine whether atezolizumab plus carboplatin improved survival outcomes for patients with metastatic TNBC compared to carboplatin alone.

The study enrolled 106 patients (100% women; mean age, 55 years; 69% White) whom the researchers assigned to carboplatin (area under the curve, 6), either alone (n = 50) or with intravenous atezolizumab at (1,200 mg; n = 56). Treatment continued every 3 weeks until disease progression or intolerable toxicity, with a follow-up period lasting 3 years.

At the time of PFS data cutoff, 88.7% of patients (n = 94) had died or experienced disease progression. The median duration of follow-up was 8.9 months (range, 0.9-33.2) for patients assigned to carboplatin alone and 10.3 months (range, 0.9-30) for patients assigned to atezolizumab plus carboplatin.

Median PFS for patients assigned to atezolizumab plus carboplatin was 4.1 months (95% CI, 2.4-7), compared to 2.2 months (95% CI, 2-4.4) for carboplatin alone (hazard ratio [HR] = 0.66; 95% CI, 0.44-1.01; P = .05). Median OS also significantly favored assignment to atezolizumab (12.6 months vs 8.6 months; HR = 0.6; 95% CI, 0.37-0.96; P = .03) as did overall response rate (30.4% vs 8%) and clinical benefit rate at 6 months (37.5% vs 18%).

The researchers further noted that OS outcomes for the combination grew more robust when they excluded patients who crossed over from the carboplatin only arm (12.6 months vs 7 months; HR = 0.46; 95% CI, 0.27-0.79). The researchers did not observe a correlation between PD-L1 positivity and OS benefit with atezolizumab. The addition of atezolizumab to carboplatin was shown to improve OS regardless of PD-L1 status (HR = 0.62; 95% CI, 0.23-1.65).

However, Pietenpol and colleagues did identify subgroups that benefited especially from treatment with the combination. OS was markedly improved in patients with high pretreatment levels of tumor-infiltrating lymphocytes (HR = 0.12; 95% CI, 0.3-0.5) and higher mutational burden (HR = 0.5; 95% CI, 0.23-1.06) as well as those with prior exposure to chemotherapy (HR = 0.59; 95% CI, 0.36-0.95).

Improvements in PFS were also associated with obesity levels of BMI and on-treatment blood glucose levels above 125 mg/dL (HR = 0.35; 95% CI, 0.1-1.8). The benefits of the combination were seen in all subtypes of TNBC with the exception of the luminal A subtype.

Both treatment platforms were well tolerated. The median time on treatment for patients assigned to atezolizumab plus carboplatin was 17.4 weeks (range, 1.4-90.3), and the median time on treatment for patients assigned to carboplatin alone was 15.4 weeks (range, 3-72.1). A higher percentage of grade 3 or 4 adverse events occurred in the atezolizumab arm (41% vs 8%); however, rates of study withdrawal were similar (6% vs 4%).

“Crossover patients receiving sequential chemotherapy and immunotherapy had fewer toxic effects than patients receiving the combination, suggesting sequential treatment could be considered for patients whose treatment-related toxic effects are of concern,” the researchers concluded.

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Disclosures: Some authors declared financial ties to drugmakers. See full study for details.  

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