Adjuvant atezolizumab ’very unlikely’ to improve DFS in triple-negative breast cancer
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Key takeaways:
- The addition of atezolizumab to chemotherapy did not extend PFS in the overall cohort.
- Results showed no benefit in subgroups based on PD-L1 or nodal status.
SAN ANTONIO — The addition of atezolizumab to adjuvant chemotherapy “is very unlikely” to improve DFS for women with stage II or stage III triple-negative breast cancer, according to data presented at San Antonio Breast Cancer Symposium.
“[Analysis of] the primary endpoint together with secondary efficacy endpoints do not support the addition of atezolizumab to adjuvant chemotherapy [for] patients who have undergone primary surgery for early triple-negative breast cancer,” Michail Ignatiadis, MD, director of the breast medical oncology clinic and program at Institut Jules Bordet, said during a presentation.
Background and methods
The randomized phase 3 ALEXANDRA/IMpassion030 study evaluated the efficacy, safety and pharmacokinetic profile of adding adjuvant atezolizumab (Tecentriq, Genentech) — an anti-PD-L1 monoclonal antibody — to standard anthracycline/taxane chemotherapy for patients with early-stage triple-negative breast cancer.
The analysis included 2,199 patients with operable stage II or stage III triple-negative breast cancer confirmed via central pathology review.
Researchers randomly assigned 1,101 of them (median age, 53 years; range, 24-86) to the investigational regimen. It consisted of adjuvant chemotherapy — 80 mg/m2 paclitaxel weekly for 12 weeks, followed by dose-dense anthracycline (90 mg/m2 epirubicin or 60 mg/m2 doxorubicin) and 600 mg/m2 cyclophosphamide for four doses every 2 weeks — with simultaneous atezolizumab (840 mg every 2 weeks, followed by 1,200 mg maintenance atezolizumab every 3 weeks until they had received the agent for 1 year).
The other 1,098 participants (median age, 53 years; range, 23-79) received chemotherapy alone.
Invasive DFS served as the primary control, while secondary endpoints included invasive DFS in the PD-L1 positive and lymph node-positive subpopulations, OS, safety, patient functioning and health-related quality of life.
Researchers stratified via type of surgery, nodal status and centrally assessed PD-L1 status.
Results, next steps
Results showed the addition of atezolizumab to adjuvant chemotherapy did not significantly improve invasive DFS.
At median follow-up of 25.3 months, 239 (10.9%) invasive DFS events occurred in the cohort (investigative arm, n = 127; control arm, n = 112), translating to an HR of 1.12 (95% CI, 0.87-1.45).
Among patients with PD-L1-positive disease (n = 1,567), 150 events occurred (investigative arm, n = 77; control arm, n = 73), translating to an HR of 1.03 (95% CI, 0.75-1.42).
Among patients with lymph node-positive tumors (n = 1,066), 152 events occurred (investigative arm, 86; control arm, n = 66), translating to an HR of 1.41 (95% CI, 1.02–1.96).
Grade 3 or higher adverse events occurred among 58% of patients assigned the investigational intervention and 48.1% of those assigned chemotherapy alone.
Researchers reported two (0.2%) treatment-related deaths in the atezolizumab group and one (< 0.1%) in the chemotherapy-alone group.
Study data will be updated based on a later clinical cutoff date and final results will be published when available, Ignatiadis said. Translational research into the dataset also will be conducted.
“[Despite the negative results], the ALEXANDRA/IMpassion030 trial contributes to an improved understanding about the optimal use of immunotherapy in patients with early triple-negative breast cancer,” Ignatiadis said.
Perspective
Back to TopLaura Huppert, MD
These data do not support the addition of adjuvant atezolizumab to chemotherapy for patients who have undergone primary surgery for early-stage triple-negative breast cancer. Instead, the neoadjuvant use of immunotherapy is clearly preferred.
What are the potential reasons for lack of benefit with adjuvant atezolizumab? First, it could certainly be due to the lack of primary tumor at the time of administration, resulting in less robust T-cell activation. Second, it’s possible atezolizumab underperformed, as it did in the metastatic setting, and outcomes may have been different with a PD-1 inhibitor. We’ll await EFS data from the GeparDouze trial to understand the role of atezolizumab in breast cancer. More definitive data regarding immunotherapy timing may come from other pending adjuvant immuno-oncology trials, such as S1418, which is evaluating adjuvant pembrolizumab (Keytruda, Merck) for early-stage triple-negative breast cancer with residual disease after neoadjuvant chemotherapy.
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Ignatiadis M, et al. Abstract GS01-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023, San Antonio.
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