KEY TAKEAWAYS
- The phase 3 KEYNOTE-522 (NCT03036488) trial evaluated the efficacy of pembrolizumab in combination with chemotherapy for patients diagnosed with early triple-negative breast cancer.
- The study used a randomized 2:1 ratio to administer pembrolizumab or placebo in combination with chemotherapy to 1174 patients.
- The study outcomes demonstrated significant enhancements in pCR and EFS with pembrolizumab.
- An elevated RCB score was observed to be correlated with poorer EFS. Patients with residual disease exhibited lower RCB values in the pembrolizumab arm.
- The study suggests that administering neoadjuvant therapy with pembrolizumab can enhance survival among patients with early triple-negative breast cancer.
The clinical trial KEYNOTE-522 (NCT03036488) evaluated the efficacy of pembrolizumab (pembro) in combination with chemotherapy (chemo) for patients (pts) diagnosed with early triple-negative breast cancer (TNBC). The primary outcomes demonstrated statistically significant and clinically meaningful enhancements in complete pathological response (pCR) and event-free survival (EFS) with pembrolizumab. Previous research has shown the prognostic significance of the residual cancer burden (RCB) technique in measuring the degree of remaining disease following neoadjuvant chemotherapy. In this preliminary investigation, we evaluated event-free survival by residual cancer burden in the KEYNOTE-522 study.
A total of 1174 patients who had not received prior treatment and had nonmetastatic, stage T1c/N1-2, or T2-4/N0-2 triple-negative breast cancer were subjected to a randomization process in a 2:1 ratio. The patients were administered either 200 mg of pembrolizumab every three weeks or a placebo, combined with four cycles of paclitaxel and carboplatin, followed by four cycles of doxorubicin or epirubicin and cyclophosphamide. After the curative surgical intervention, patients were administered either pembrolizumab or a placebo for nine cycles or until disease relapse or adverse reactions were deemed intolerable. The study’s dual primary endpoints include complete pathological response and event-free survival . The attending pathologist evaluated the regional lymph node basin during the surgical procedure. The correlation between RCB categories (RCB-0, -1, -2, -3, which correspond to progressively larger residual cancer) and Event-Free Survival (EFS) was evaluated using a Cox regression model, with treatment as a covariate.
The median duration of follow-up was 39.1 months as of the data cutoff date of March 23, 2021. Pembrolizumab was observed to cause a reduction in the risk of recurrence in patients with resected stage III melanoma across all categories of risk (as indicated in the Table). The hazard ratios (95% confidence intervals) for event-free survival were 0.70 (0.38 – 1.31) for Residual Cancer Burden (RCB)-0 (equivalent to complete pathological response), 0.92 (0.39 – 2.20) for RCB-1, 0.52 (0.32 – 0.82) for RCB-2, and 1.24 (0.69 – 2.23) for RCB-3. The most prevalent event of EFS observed in both groups was a distant recurrence, with a lower incidence observed in patients receiving pembrolizumab across all Residual Cancer Burden categories.
An elevated Red Cell Distribution Width score was observed to be correlated with poorer Event-Free Survival. Patients with residual disease exhibited lower Residual Cancer Burden values in the pembrolizumab arm, with fewer patients presenting RCB-3. The combination of Pembrolizumab and chemotherapy resulted in a prolonged Event-Free Survival compared to chemotherapy alone in patients belonging to RCB-0, -1, and -2 categories. However, the interpretation of results in the RCB-3 category is limited due to the small sample size. The cohort of patients exhibiting significant remaining disease (RCB-3) in both study groups, comprising 5.1% and 6.7% of the total population, demonstrated an unfavorable medical outlook. The findings above emphasize the significance of administering neoadjuvant therapy with pembrolizumab to enhance survival among patients with early triple-negative breast cancer. Additionally, the study identified a subgroup of patients requiring supplementary therapeutic interventions.
Source: https://meetings.asco.org/abstracts-presentations/208272
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03036488
Lajos Pusztai, Carsten Denkert, Joyce O’Shaughnessy, Javier Cortes, Rebecca Alexandra Dent, Heather L. McArthur, Sherko Kuemmel, Jonas C. S. Bergh, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Michael Untch, Peter A. Fasching, Fatima Cardoso, Yalin Zhu, Wilbur Pan, Konstantinos Tryfonidis, Peter Schmid/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 40, 2022 (suppl 16; abstr 503) DOI10.1200/JCO.2022.40.16_suppl.503
