Combining Atezolizumab with Neoadjuvant Chemotherapy Does Not Improve Pathologic Complete Response Rates for Patients with Triple-Negative Breast Cancer

SAN ANTONIO — The addition of the anti-PD-L1 immunotherapeutic atezolizumab (Tecentriq) to neoadjuvant chemotherapy for patients with triple-negative breast cancer (TNBC) did not improve the rate of pathologic complete response when compared to chemotherapy alone, according to preliminary results from the NeoTRIPaPDL1 trial, which were presented at the San Antonio Breast Cancer Symposium, held Dec. 10-14.

“TNBC is an aggressive subtype of breast cancer with a high probability of relapsing,” said Luca Gianni, MD, president of the Fondazione Michelangelo in Milan. “Currently, the only treatment for early-stage TNBC is chemotherapy. While chemotherapy can be successful in some patients, relapse and resistance to chemotherapy are common, even after good initial responses.”

In this study, Gianni and colleagues examined the effect of adding theimmune checkpoint inhibitor atezolizumab to neoadjuvant chemotherapy. “TNBC tumors often harbor immune cells called lymphocytes,” explained Gianni. “We reasoned that treating patients with an immune checkpoint inhibitor, in combination with chemotherapy, could boost the antitumor immune response.” Atezolizumab in combination with the chemotherapy drug nab-paclitaxel is currently approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of some patients with locally advanced or metastatic TNBC.

The study enrolled 280 female patients, aged 18 or older, with early high-risk and locally advanced or inflammatory TNBC. Patients were randomly assigned to receive neoadjuvant carboplatin and nab-paclitaxel (Abraxane), which are both chemotherapy drugs, with or without atezolizumab. The primary aim of the study, which is ongoing, is to determine five-year event-free survival rates. The secondary aim is to determine the rate of pathologic complete response, which can be a good predictor of long-term outcomes, explained Gianni.

Gianni and colleagues reported the data on pathologic complete response. They found that the addition of atezolizumab to neoadjuvant chemotherapy for approximately six months resulted in slightly higher rates of pathologic complete response when compared to neoadjuvant chemotherapy alone in the intent-to-treat population (43.5 percent vs. 40.8 percent); however, the increase was not statistically significant. Among patients whose tumors tested positive for PD-L1, 51.9 percent of patients in the atezolizumab plus chemotherapy arm had pathologic complete responses compared to 48.0 percent of those in the chemotherapy only arm, but this difference was also not significant.

“Our observations may indicate that there is no therapeutic benefit to adding atezolizumab to neoadjuvant chemotherapy compared to chemotherapy alone, or it may simply mean that any beneficial effects of the combination will be seen in the long term,” said Gianni. “Pathologic complete response does not provide information about the quality of response, which is why we did not use it as the primary endpoint for this study. Further analyses may reveal differences in the quality of response between the treatment groups.”

Biological samples collected from patients before, during, and after neoadjuvant treatment will be examined for lymphocyte infiltration, DNA mutations, and/or levels of circulating tumor DNA, which may reveal differences between the treatment groups, added Gianni.

Gianni and colleagues also reported that atezolizumab was well tolerated in the majority of enrolled patients. Immune-mediated adverse events of any grade were observed in approximately 8 percent of patients. Infusion reactions were the most commonly observed immune-mediated adverse event, and approximately 1.4 percent of infusion reactions were grade 3 or higher.

A limitation of the study is that the reported results are limited to the initial effects of the combination treatment and do not account for the effects of therapies administered after surgery.

This study was sponsored by Roche and Celgene. Gianni has served advisory roles for ADC Therapeutics, AstraZeneca, Celgene, Eli Lilly, G1 Therapeutics, Genentech, Genomic Health, MSD, Oncolytics Biotech, Odonate Therapeutics, Onkaido Therapeutics, Roche, Pfizer, Taiho Pharmaceutical, Sandoz, Seattle Genetics, Synthon, and Zymeworks. Gianni has consulted for Forty Seven Inc., Genenta Science, METIS Precision Medicine, Novartis, Odonate Therapeutics, Revolution Medicines, Synaffix, and Zymeworks. Gianni has received support for research from Zymeworks, Daiichi Sankyo, Zymeworks, and Revolution Medicines. Gianni is a co-inventor on a patent for PD-L1 expression in anti-HER2 therapy.