Lajos Pusztai, MD, DPhil, discusses multiple analyses of the phase 3 KEYNOTE-522 clinical trial of pembrolizumab plus chemotherapy administered in the neoadjuvant or adjuvant setting to patients with triple-negative breast cancer versus placebo plus chemotherapy.
Lajos Pusztai, MD, DPhil, professor of Medicine (Medical Oncology), and co-leader of Genetics, Genomics, and Epigenetics at Yale Cancer Center, discusses multiple analyses of the phase 3 KEYNOTE-522 (NCT03036488) clinical trial of pembrolizumab (Keytruda) plus chemotherapy administered in the neoadjuvant or adjuvant setting to patients with triple-negative breast cancer (TNBC) versus placebo plus chemotherapy.
In prior analyses of KEYNOTE-522, pembrolizumab demonstrated pathologic complete responses in the first 603 patients out of 1174, meeting 1 of its primary end points. In comparison with chemotherapy alone, the pCR improvement was approximately 13%, according to Pusztai.
The second primary end point of event-free survival was also met during an interim analysis. Eight-five percent of patients in the pembrolizumab had EFS events compared with 77% in the placebo arm.
During the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, updated findings presented by Pusztai showed that an increased residual cancer burden (RCB) score correlated with worse EFS in patients with TNBC, however, there was an EFS improvement with pembrolizumab/chemotherapy vs the control arm in patients with lower RCB scores.1
0:08 | KEYNOTE-522 is the largest neoadjuvant/adjuvant trial via immune checkpoint inhibitor in triple-negative breast cancer. The trial design included approximately 20 to 24 weeks of neoadjuvant chemotherapy with weekly taxol followed by regular adriamycin/ cyclophosphamide, or epirubicin/cyclophosphamide chemotherapy, either without or with every 3-week pembrolizumab.
0:38 | And after surgery patients continued with pembrolizumab or a placebo. So, this was a double-blind, placebo-controlled, phase 3, randomized trial that included overall 1174 patients. The primary endpoints included both pathologic complete response rate during the neoadjuvant phase and event-free survival in the combined neoadjuvant followed by adjuvant phases of the study. And the preplanned first primary outcome analysis was done after the first 602 patients had pathological complete response.
1:20 | The study has met its primary endpoint. For this outcome, it showed a pathological complete response rate improvement of approximately 13% compared to chemotherapy alone. And subsequently, in the fourth interim analysis, which was again a preplanned statistical analysis, the second primary end point [of] event-free survival was also met. Overall, 85% or close to 85% of the patients in the pembrolizumab arm were event free compared to 77% in the placebo arm. Again, this represents about 8% improvement in event-free survival.
2:01 | So, what I presented at the ASCO was the updated results now including pathological complete response rates and the distribution of residual cancer burden in the entire study population. It also showed the event-free survival by residual disease categories.
Pusztai L, Denkert C, O'Shaughnessy J, et al. Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522. J Clin Oncol. 2022; 40 (suppl 16; abstr 503). doi: 10.1200/JCO.2022.40.16_suppl.503