Atezolizumab regimen boosts response among certain women with breast cancer
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Key takeaways:
- Researchers reported no statistically significant difference in complete response rates between the two main treatment arms.
- Study continues follow-up to determine event-free survival.
SAN ANTONIO — The addition of atezolizumab to chemotherapy, trastuzumab and pertuzumab did not significantly increase pathologic complete response rates among women with HER2-positive breast cancer.
However, exploratory analysis of the data presented at San Antonio Breast Cancer Symposium showed that adding atezolizumab to neoadjuvant anthracycline and cyclophosphamide — followed by trastuzumab, pertuzumab, carboplatin and paclitaxel — did lead to higher pathologic complete response (pCR) rates, when compared with trastuzumab, pertuzumab, carboplatin and paclitaxel plus atezolizumab alone.
“The addition of atezolizumab to chemotherapy and trastuzumab plus pertuzumab led to a 5.8% nonstatistically significant numerical increase of pCR in women with HER2-positive operable breast cancer,” Luca Gianni, MD, director of the medical oncology department at San Raffaele Scientific Institute in Milan, said during a presentation.
Background and methodology
The current standard of care for patients with high-risk HER2-positive breast cancer is neoadjuvant dual targeting of HER2 with trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech) with chemotherapy.
Current research data support the potential combination of immune checkpoint inhibitors with anti-HER2 antibodies due to the contribution of the immune system in prognosis and response or resistance to HER2-directed therapies.
Therefore, researchers conducted the open-label phase 3 APTneo trial to evaluate the efficacy of adding atezolizumab (Tecentriq, Genentech) — an anti-PD-L1 monoclonal antibody — to neoadjuvant dual targeting of HER2 plus chemotherapy. The study also analyzed the potential value of adding anthracyclines for the study’s patient population.
Researchers randomly assigned 661 women with high-risk early and locally advanced HER2-positive breast cancer to receive neoadjuvant trastuzumab, pertuzumab, carboplatin and paclitaxel (HPCT) without (n = 223, arm A) or with 1,200 mg atezolizumab (n = 438, arm B).
Study investigators further randomly assigned patients in arm B to receive anthracycline and cyclophosphamide plus atezolizumab followed by HPCT and atezolizumab (n = 218, arm B1) or HPCT plus atezolizumab (n = 220, arm B2).
After surgery, patients continued adjuvant HER2-directed therapies either with or without atezolizumab for 1 year. Among patients in the intent-to-treat cohort, 44.8% had locally advanced breast cancer, 35% had HR-negative breast cancer and 30.4% had PD-L1–positive breast cancer.
Event-free survival of arm B vs. arm A served as the study’s primary endpoint, with a key secondary endpoint of pCR rate with vs. without atezolizumab. The intent-to-treat cohort comprised the primary population for all efficacy endpoints.
Results, next steps
Researchers reported a pCR rate of 57.8% in arm B vs. 52% in arm A (adjusted HR = 1.33; 95% CI, 0.95-1.86).
Additionally, study investigators noted a difference in pCR rates between arm B1 (61.9%) and B2 (53.6%) that did not achieve statistical significance (adjusted HR = 1.402; 95% CI, 0.95-2.07).
When compared with arm A, arm B1 had a significantly higher (+9.9%) pCR rate.
Difference in pCR rate between arms B1 and A appeared similar regardless of hormone receptor and PD-L1 status, according to researchers.
They also reported serious adverse events after beginning therapy in 6.8% of patients in arm A and 14.1% of patients in arm B; serious adverse events occurred more frequently in arm B1 (16.7%) than in arm B2 (11.6%). Immune-related serious adverse events appeared similar for both arms B1 (4.7%) and B2 (7.8%). No grade 5 adverse events occurred during the study.
“An exploratory analysis shows a statistically significant higher rate of pCR (9.9%) with atezolizumab added to [anthracycline and cyclophosphamide] followed by HPTC compared to control HPCT, suggesting either a direct anthracycline effect or a mechanistic enhancement of [anthracycline and cyclophosphamide] with atezolizumab,” Gianni said. “The study continues follow-up until analysis of the primary endpoint of event-free survival.”
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Gianni L, et al. Abstract LB01-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.
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