Atezolizumab/Chemo Combo Yields Survival Benefit in Metastatic TNBC

Those who enrolled on the study were treated with either single agent carboplatin at area under the curve 6 or carboplatin plus 1200 mg of atezolizumab every 3 weeks until progression, unacceptable toxicity, or withdrawal.

Combining atezolizumab (Tecentriq) and carboplatin resulted in a statistically significant survival benefit in patients diagnosed with metastatic triple-negative breast cancer (TNBC) irrespective of PD-L1 expression, according to a readout of data from the phase 2 TBCRC043 trial (NCT03206203).

Patients who were treated with the combination experienced a benefit in median progression-free survival (PFS) from 2.2 months to 4.1 months (HR, 0.66; 95% CI, 0.44-1.01; P = .05). Additionally, overall response rate (ORR) increased from 8.0% (95% CI, 3.2%-18.8%) to 30.4% (95% CI, 19.9%-43.3%). Investigators also reported a clinical benefit rate (CBR) that increased from 18.0% (95% CI, 9.8%-30.1%) to 37.5% (95% CI, 26.0%-50.6%) at 6 months. Lastly, median overall survival (OS) jumped from 8.6 months to 12.6 months (HR, 0.60; 95% CI, 0.37-0.96; P = .03).

“In this multicenter phase 2 randomized clinical trial, adding atezolizumab to carboplatin significantly increased PFS and OS in patients with metastatic TNBC,” the study authors wrote. “Increased [tumor infiltrating lymphocytes], higher [tumor mutational burden], obesity, and uncontrolled blood glucose levels were associated with a decreased risk of progression, whereas tumor HLA-A expression, PIK3CA variants, and the LAR subtype were associated with a greater risk of progression for patients receiving the combination.”

The prospective, multicenter, double-blind phase 2 study included patients with clinical stage IV or metastatic invasive disease that was estrogen receptor, progesterone receptor, and ERBB2 negative. Additionally, the study included those with an ECOG performance status of 0 to 1 with adequate hematologic, kidney, hepatic, and cardiac function. Patients needed to have received no or 1 previous treatment for metastatic disease, as well as have not previously received carboplatin for metastatic disease.

Those who enrolled on the study were treated with either single agent carboplatin at area under the curve 6 or carboplatin plus 1200 mg of atezolizumab every 3 weeks until progression, unacceptable toxicity, or withdrawal.

The study’s primary end point was PFS, with secondary end points including ORR, CBR, duration of response, and OS.

A total of 130 patients were included in the study between August 8, 2017, and October 6, 2020. The mean patient age was 55 years (range, 27-79), and most were White (69%) and Black (19%). Eighteen percent and 20% of patients in the atezolizumab and carboplatin cohorts, respectively, were PD-L1 positive. Previously, 87% of patients were treated with chemotherapy, 33% with adjuvant treatment, 32% with metastatic treatment, and 20% with neoadjuvant and adjuvant treatment.

As of the PFS cut-off date of October 2021, 88.7% of patients had progressed or died. The median follow-up was 8.9 months (range, 0.9-33.2) in the carboplatin cohort compared with 10.3 months (range, 0.9-30.0) in the combination cohort.

The median duration of treatment in the experimental arm was 17.4 months (range, 1.4-90.3) compared with 15.4 months (range, 3.0-72.1) in the carboplatin arm. Any grade adverse effects (AEs) in the experimental arm consisted of thrombocytopenia, anemia, lymphocytopenia, nausea, fatigue, and liver enzyme increase. Notably, treatment was atezolizumab/carboplatin associated with a higher rate of grade 3/4 serious AEs (41%) compared with the carboplatin arm (8%).

Reference

Lehmann BD, Abramson VG, Dees EC, et al. Atezolizumab in combination with carboplatin and survival outcomes in patients with metastatic triple-negative breast cancer. JAMA Oncol. Published online December 14, 2023. doi:10.1001/jamaoncol.2023.5424