Atezolizumab fails to improve response in triple-negative breast cancer
Click Here to Manage Email Alerts
SAN ANTONIO — The addition of atezolizumab to neoadjuvant chemotherapy failed to improve pathologic complete response rate for patients with triple-negative breast cancer, according to preliminary results from the randomized NeoTRIPaPDL1 Michelangelo study presented at San Antonio Breast Cancer Symposium.
Multivariate analysis identified the presence of PD-L1 expression as the most significant factor for influencing pathologic complete response rate regardless of treatment regimen.
“Treatment-related adverse events were similar with [both regimens] except for a significantly higher overall incidence of serious adverse events and liver function test abnormalities with atezolizumab,” researcher Luca Gianni, MD, president of Fondazione Michelangelo in Milan, Italy, said during a press conference. “Continuous follow-up for the primary endpoint of EFS and other efficacy endpoints is ongoing, and molecular studies are underway.”
Triple-negative breast cancers are associated with poor prognosis, in part because they rapidly progress to distant metastases and develop resistance to chemotherapy. PD-1/PD-L1 blockade may induce durable responses in this patient population alone or in combination with chemotherapy, according to study background.
Also, results of the IMpassion130 study showed the addition of the anti-PD-L1 antibody atezolizumab (Tecentriq, Genentech) to nab-paclitaxel conferred significant PFS and OS benefits for patients with PD-L1-positive metastatic triple-negative breast cancer, according to study background.
The NeoTRIPaPDL1 study included 280 women with HER2-negative, ER- and PR-negative, early high-risk or locally advanced unilateral breast cancer.
Gianni and colleagues randomly assigned 142 women (median age, 50 years; range, 24-77) to eight cycles of carboplatin (area under the curve, 2) plus nab paclitaxel 125 mg/m2 weekly in a 2-weeks-on, 1-week-off schedule. The other 138 women (median age, 49.5 years; range, 25-79) received the same chemotherapy regimen plus atezolizumab on day 1 of each treatment cycle.
EFS at 5 years after randomization of the last patient served as the study’s primary outcome.
Treatment groups were well-balanced with regard to disease stage, PD-L1 positivity, T stage and nodal status.
Results showed a higher numerical pathological complete response rate among atezolizumab-treated women (43.5% vs. 40.8%), but the difference did not reach statistical significance (OR = 1.11; 95% CI, 0.69-1.79).
Multivariate analysis showed PD-L1-positive disease predicted treatment benefit with atezolizumab compared with PD-L1 negativity (OR = 2.08; 95% CI, 1.64-2.65). Disease stage did not predict treatment effect (early high-risk disease vs. locally advanced disease, OR = 0.84; 95% CI, 0.66-1.06).
Researchers reported overall response rates of 76.1% with atezolizumab and 68.3% with chemotherapy alone. A higher percentage of women assigned atezolizumab achieved complete response (29% vs. 26.1%) or partial response (47.1% vs. 42.3%), whereas women assigned chemotherapy alone were more likely to have stable disease (4.9% vs. 3.6%) or progressive disease (8.4% vs. 5.8%).
An analysis of treatment-related adverse events showed a higher percentage of women assigned atezolizumab developed infusion reactions (any grade, 8% vs. 5.7%; grade 3 or higher, 1.4% vs. 0.7%), hypothyroidism (any grade, 5.8% vs. 1.4%), thyroiditis (any grade, 1.5% vs. 0%), colitis (any grade, 1.5% vs. 0.7%), hyperthyroidism (any grade, 0.7% vs. 0%) and interstitial nephritis (any grade, 0.7% vs. 0%). Rates of pancreatitis (1.5% each), Coombs-positive hemolytic anemia (0.7% each) and thrombotic thrombocytopenic purpura (0.7% each) were the same in both groups.
Gianni and colleagues acknowledged the findings are limited due to the fact that the reported results only focus on initial effects of the combination therapy and do not account for their effects when administered after surgery.
“Our observations may indicate that there is no therapeutic benefit to adding atezolizumab to neoadjuvant chemotherapy compared [with] 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 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.” – by Mark Leiser
Reference:
Gianni L, et al. Abstract GS3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosures: Celgene and Roche sponsored this study. Gianni reports consultant/advisory roles with or research support from ADC Therapeutics, AstraZeneca, Celgene, Daiichi Sankyo, Eli Lilly, Forty Seven Inc., G1 Therapeutics, Genenta Science, Genentech, Genomic Health, Merck Sharp & Dohme, METIS Precision Medicine, Novartis, Odonate Therapeutics, Oncolytics Biotech, Onkaido Therapeutics, Pfizer, Revolution Medicines, Roche, Sandoz, Seattle Genetics, Synaffix, Synthon, Taiho Pharmaceutical and Zymeworks. He also is a co-inventor on a patent for PD-L1 expression in anti-HER2 therapy. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to Top
Kevin Kalinsky, MD, MS
The primary endpoint of the NeoTRIPaPDL1 study was EFS; however, researchers did not present those data. They presented data related to pathologic complete response, a key secondary endpoint. Results showed no statistically significant difference. They also show that those who have PD-L1-positive tumors seem to benefit from the combination, but we’re seeing that PD-L1 positivity may reflect just a benefit from chemotherapy alone. It ultimately will be intriguing to see — despite the fact we are not seeing pathologic complete response improvement now — whether we will see an EFS benefit. That requires longer-term follow-up.
Click Here to Manage Email Alerts