IMpassion031 Final Results: ctDNA Dynamics Add Prognostic Value Beyond Pathologic Response in TNBC
Final analysis of the phase 3 IMpassion031 trial confirms favorable long-term outcomes when adding atezolizumab to neoadjuvant chemotherapy for stage II/III triple-negative breast cancer (EFS HR 0.76, OS HR 0.56). Exploratory ctDNA analyses revealed that ctDNA-positive status at surgery identified a subset of non-pCR patients with the poorest prognosis, demonstrating that ctDNA dynamics provide prognostic value beyond the pCR endpoint.
The original study
Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial.
- Authors
- Mittendorf EA, Assaf ZJ, Harbeck N, Zhang H, Saji S, Jung KH, et al.
- Journal
- Nature medicine
- Type
- Journal Article, Randomized Controlled Trial, Clinical Trial, Phase III, Multicenter Study
- PMID
- 40467898
Original abstract
Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years' follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (n = 165) or preoperative placebo (n = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47-1.21; disease-free survival HR, 0.76; 95% CI, 0.44-1.30; overall survival HR, 0.56; 95% CI, 0.30-1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935 .