Adding Immunotherapy to Chemo Before Surgery May Not Improve Response Rates in TNBC

Although combined immunotherapy and chemotherapy are approved to treat advanced triple-negative breast cancer, adding the immune-stimulating drug Tecentriq (atezolizumab) to chemotherapy before surgery did not improve the rate of pathologic complete response in patients with earlier-stage disease.

The finding from the NeoTRIPaPDL1 Michelangelo trial was presented at the San Antonio Breast Cancer Society’s (SABCS) annual meeting, which took place Dec. 10-14. Launched in 2015, the primary goal of the study is to compare the percentage of participants on each treatment regimen who experience specific negative health events five years after enrollment of the last patient. The study is fully enrolled, but those results have not yet been collected; during the conference, the study’s lead author presented strictly about a secondary goal of the trial, to measure pathologic complete response, which can be a good predictor of long-term outcomes. Pathologic complete response means there is no remaining invasive disease detectable in the breast or axillary lymph nodes after presurgical treatment.

Triple-negative breast cancer is an aggressive subtype which, compared with other subtypes, has a higher probability of recurring, according to Dr Luca Gianni, president of the Fondazione Michelangelo in Milan, Italy. “Currently, the only treatment for early-stage triple-negative breast cancer is chemotherapy. While chemotherapy can be successful in some patients, relapse and resistance to chemotherapy are common, even after good initial responses,” he said in a press release.

The study enrolled 280 female patients over the age of 18 who had early high-risk and locally advanced or inflammatory triple-negative breast cancer. These patients were randomly assigned to received neoadjuvant (presurgical) carboplatin and nab-paclitaxel (Abraxane), which are both chemotherapy drugs, with or without Tecentriq. After surgery, they took four rounds of abraxane chemotherapy.

The research team embarked on the study because they knew that triple-negative breast cancer sometimes harbors immune cells called lymphocytes that can help fight the disease. Furthermore, Tecentriq in combination with chemotherapy has been approved by the Food and Drug Administration to treat some patients with locally advanced or metastatic triple-negative breast cancer.

“We reasoned that treating patients with an immune checkpoint inhibitor, in combination with chemotherapy, could boost the antitumor immune response” in these patients, Gianni said in the release.

When results were calculated, Gianni and colleagues found that the addition of Tecentriq to neoadjuvant chemotherapy over the course of about six months did not result in a statistically significant difference in pathologic complete response when compared to neoadjuvant chemotherapy alone (43.5% versus 40.8%, respectively), meaning the results were not greater than what could be expected by chance.

“Our observations may indicate that there is no therapeutic benefit to adding (Tecentriq) 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,” Gianni said. “Pathologic complete response does not provide information about the quality of the 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 treatment groups.”

The researchers found that Tecentriq was well tolerated in most enrolled patients. Immune-related side effects of any severity were seen in about 8% of patients. Of those, reactions to infusion of the drug were the most common, with 1.4% reaching the level of serious or worse. There were more serious side effects and more abnormal liver function tests among the patients taking chemotherapy with immunotherapy.

Forthcoming results from the study could shed more light on its potential role in treating earlier-stage triple-negative breast cancer. “We will continue to follow up for the primary endpoint of event-free survival,” Gianni said during a press briefing at SABCS. “Other efficacy endpoints and molecular studies are underway.”