Neoadjuvant atezolizumab, chemotherapy improve outcomes in triple-negative breast cancer
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The addition of atezolizumab to neoadjuvant chemotherapy improved pathologic complete response rates regardless of PD-L1 expression in early triple-negative breast cancer, according to data presented at ESMO Virtual Congress 2020.
These data from the IMpassion031 trial also showed the combination of atezolizumab (Tecentriq, Genentech/Roche) to paclitaxel protein-bound particles for injectable suspension (Abraxane, Celgene), doxorubicin and cyclophosphamide had a manageable safety profile.
“Stage I to III triple-negative breast cancer accounts for 10% to 20% of new diagnoses of early breast cancer,” Nadia Harbeck, MD, PhD, head of the Breast Centre and chair of conservative oncology in the department of obstetrics and gynecology at LMU University Hospital in Germany, said during her presentation.
“IMpassion130 showed that atezolizumab combined with nab-paclitaxel provided a PFS benefit and a clinically meaningful OS benefit for PD-L1-positive metastatic triple-negative breast cancer with an acceptable safety profile vs. nab-paclitaxel alone,” she added. “IMpassion031 is a phase 3 trial evaluating the efficacy and safety of atezolizumab vs. placebo in combination with neoadjuvant chemotherapy for treatment of early-stage triple-negative breast cancer.”
The analysis included 333 treatment-naive women with triple-negative breast cancer who researchers randomly assigned to receive sequential chemotherapy consisting of 125 mg/m2 IV nab-paclitaxel weekly for 12 weeks followed by 60 mg/m2 IV doxorubicin plus 600 mg/m2 IV cyclophosphamide every 2 weeks for 8 weeks plus placebo (n = 168; median age, 50.5 years; 64.3% white) or 840 mg IV atezolizumab (n = 165; median age, 51 years; 61.8% white) every 2 weeks throughout the chemotherapy treatment. Following surgery, those in the atezolizumab cohort received 11 additional doses at 1,200 mg every 3 weeks.
Pathologic complete response in the intention-to-treat and PD-L1-positive subgroups served as the study’s co-primary endpoints. Secondary endpoints included EFS, DFS and OS in those subgroups.
“Originally, the study had a single endpoint of pathologic complete response in an all-comer population,” Harbeck said. “However, during the conduct of the IMpassion031 trial, the IMpassion130 trial in metastatic breast cancer showed benefit only in PD-L1-positive patients. Thus, there was a potential concern that atezolizumab may have benefit only in PD-L1-positive tumors, and a decision was made to amend the 031 study and incorporate an adaptive design.”
After the first 205 patients were enrolled, the independent data monitoring committee evaluated the data and recommended continued enrollment of an all-comer population.
Median follow-up was 20.6 months for the atezolizumab-chemotherapy group and 19.8 months for the placebo-chemotherapy group.
Results showed more patients assigned the atezolizumab-chemotherapy combination achieved pathologic complete response in the intent-to-treat population (57.6% vs. 41.1%; P = .0044), and among both the PD-L1-positive (68.8% vs. 49.3%; P = .021) and -negative (47.7% vs. 34.4%) subgroups.
The 16.5-percentage point increase in the all-comer population was significant and clinically meaningful, Harbeck said. However, the difference in the PD-L1 subgroups did not meet the significance threshold of P = .0184.
“In hindsight, the decision by the independent data monitoring committee to continue enrollment in an all-comer population was correct, as we observed a significant treatment benefit in the intent-to-treat population,” Harbeck said.
Medians were not yet reached for EFS (HR = 0.76; 95% CI, 0.4-1.44), DFS (HR = 0.74; 95% CI, 0.32-1.7) and OS (HR = 0.69; 95% CI, 0.25-1.87) but favored the atezolizumab treatment group.
The incidence of grade 3 to grade 4 adverse events appeared comparable between the atezolizumab and placebo groups (62.8% vs. 60.5%), but more patients assigned atezolizumab experienced serious adverse events (30.5% vs. 18%), the most common of which were febrile neutropenia (9.8% vs. 7.8%), pneumonia (3% vs. 0.6%) and pyrexia (2.4% vs. 0%).
“This new combination therapy may offer and improved curative treatment option for this patient population with a high unmet medical need,” Harbeck said.
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Harbeck N, et al. Abstract LBA11. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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