Postoperative Checkpoint Inhibitors for Early-Stage Triple-Negative Breast Cancer?

Immunotherapy improves outcomes for patients with early-stage triple-negative breast cancer (TNBC), but how to optimally use it and in which patients remain open questions. The KEYNOTE-522 trial showed that the addition of pembrolizumab to preoperative chemotherapy increased pathological complete response rate and improved event-free and overall survival (NEJM JW Oncol Hematol Feb 11 2022 and N Engl J Med 2022; 386:556). Trial participants continued pembrolizumab postoperatively, although the contribution of the postoperative component to overall outcome is still debated.

There are patients who undergo surgery as a first step, either by design or because they do not meet the eligibility criteria for the KEYNOTE-522 regimen, but their pathology results suggest they may have been appropriate candidates for the regimen. Would postoperative immunotherapy confer benefit in this situation?

Investigators report results from the industry-sponsored, phase 3 ALEXANDRA/IMpassion030 study in which 2199 patients with stage II or III TNBC who underwent surgery as the initial treatment were randomized postoperatively to standard adjuvant chemotherapy or chemotherapy plus the checkpoint inhibitor atezolizumab for up to 1 year. The primary endpoint was invasive disease-free survival.

Patients' median age was 53 years, 52% were node negative, and 35% had 1 to 3 involved nodes. At surgery, 85% had stage II disease, 15% stage III. With a median follow-up of 32 months, the trial was stopped early after an interim analysis indicated futility. The addition of atezolizumab did not decrease recurrence rates or deaths compared with adjuvant chemotherapy alone. Furthermore, grade 3/4 toxicities were greater with the addition of immunotherapy (54% vs. 44%).