Patients with high-risk, early-stage triple-negative breast cancer (TNBC) in the phase 3 KEYNOTE-522 study (NCT03036488) with pembrolizumab (Keytruda) plus chemotherapy after surgery demonstrated event-free survival ( SSE) statistically significant, according to a press release from Merck.1
Compared with preoperative chemotherapy, an interim Data Monitoring Committee analysis revealed that neoadjuvant pembrolizumab in combination with chemotherapy followed by adjuvant monotherapy with pembrolizumab had statistically significant and clinically significant improvement in SES. This met one of the two primary endpoints of the trial, the other primary endpoint, pathologic complete response (pCR), was already achieved.
“Keytruda is the first immunotherapy to show positive results for EFS in patients with high risk early stage TNBC, a particularly aggressive form of breast cancer”, Roy Baynes, MD, PhD, senior vice president , head of global clinical development, and medical director of Merck Research Laboratories, said in a statement.
“The improvement in pCR levels initially seen after preoperative treatment was encouraging, and now that we see the data maturing after 4 years to include statistically significant improvement in EFS, we look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible. We are grateful to the study participants who are critical to our efforts to advance potential treatment options for patients with TNBC, ”concluded Baynes.
In this 2: 1, double-blind, randomized trial, 784 patients received 200 mg of pembrolizumab every 3 weeks in combination with paclitaxel and carboplatin for 4 cycles, followed by pembrolizumab plus cyclophosphamide and doxorubicin or epirubicin before surgery and then after surgery. surgery, pembrolizumab alone every 3 weeks for up to 9 cycles. Placebo was given with chemotherapy in the same schedule as the pembrolizumab group to 390 patients.
At the meeting of the European Society for Medical Oncology (ESMO) 2019 and thereafter New England Journal of Medicine, an interim analysis of pCR for these patients has been presented and published. There was a statistically significant increase in pCR for people receiving pembrolizumab among the 602 patients evaluated, with a pCR of 64.8% (95% CI, 59.9% -69.5%) versus 51.2% (95% CI, 44.1% -58.3%) in patients receiving placebo. The estimated difference was 13.6 percentage points (95% CI, 5.4-21.8; P <.001>2
At the median follow-up of 15.5 months (range 2.7 to 25.0 months) in the published data, 7.4% (n = 58/784) of patients receiving pembrolizumab and chemotherapy versus 11.98% ( n = 46/390) of those receiving placebo and chemotherapy had disease progression that died from any cause, local or distant recurrence or second primary tumor, or surgery excluded (HR, 0, 63; 95% CI, 0.43-0.93).
There were no new safety signals in the analysis of SES and the safety profile of pembrolizumab has remained consistent with previously reported studies.1 In the published data, the incidence of treatment-related Grade 3 or greater adverse events was 78.0% and 73.0% in patients receiving pembrolizumab and placebo, respectively; this included the death of 3 patients in the pembrolizumab arm and 1 patient in the placebo arm.2
In a subgroup analysis of KEYNOTE-522, a presentation at the ESMO Asia 2020 Virtual Congress showed that the combination of pembrolizumab and chemotherapy significantly increased pCR in Asian patients with TNBC.3 Of the 215 Asian patients enrolled, 136 received the pembrolizumab regimen. At the median follow-up of 13.0 months, the pCR rate among the first 125 Asian patients was 59% (95% CI, 47% -70%) in the 75 patients receiving pembrolizumab versus 40% (95% CI, 26 % -55%) in those receiving placebo.
After a 10: 0 vote by the FDA’s Oncology Drug Advisory Committee that a regulatory decision should be postponed until more data comes from KEYNOTE-522, the FDA issued Merck with a response letter completed in March 2021 for their additional biologics license application for the approval of pembrolizumab in patients with high-risk and early-stage TNBC based on pCR and early interim results from the EFS.1
Merck announces that the Phase 3 KEYNOTE-522 trial has achieved the double primary endpoint of event-free survival (ESS) in patients with early stage, high-risk triple-negative breast cancer (TNBC). Press release. Merck. Posted May 13, 2021. Accessed May 13, 2021. https://bit.ly/3brk0Hv
Schmid P, Cortes J, Pusztai L, et al; KEYNOTE-522 investigators. Pembrolizumab for early triple negative breast cancer. N Engl J Med. 2020; 382 (9): 810-821. do I:10.1056 / NEJMoa1910549
Dent R, Cortes J, Pusztai L, et al. KEYNOTE-522 Asian subgroup: phase 3 study of neoadjuvant pembrolizumab (pembro) vs placebo (pbo) + chemotherapy (chemotherapy) followed by adjuvant pembro vs pbo for early triple negative breast cancer (TNBC). Presented at: ESMO Asia Virtual Congress 2020; November 20-22, 2020. Accessed May 13, 2021. https://bit.ly/3w3jIOH