Merck’s mega-blockbuster drug Keytruda (pembrolizumab) has scored another victory with the results of KEYNOTE-826. The company has already announced that the study met its dual primary endpoints of PFS, and the detailed results presented at the presidential symposium in ESMO 2021 showed a statistically significant improvement.
KEYNOTE-826 involved the addition of Keytruda, an anti-PD-1 therapy, to the Standard of Care (SOC) platinum-based (paclitaxel with cisplatin or carboplatin) chemotherapy with or without bevacizumab. The study showed a statistically significant improvement of 33% in OS. The median OS for Keytruda plus chemotherapy arm was 24.4 months compared to 16.5 months for the chemotherapy arm, and the median PFS was 10.4 months compared to 8.2 months, respectively. The ORR improved from 50.8% to 65.9% in the Keytruda arm, and the median DOR was 18 months in the Keytruda arm compared to 10.4 months in the chemotherapy arm. The results were consistent regardless of the bevacizumab. The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of PD-L1 but not in those with biomarker-negative tumors.
There appeared to be no unexpected safety signals with the pembrolizumab combination. In the KEYTRUDA plus chemotherapy, TRAEs led to discontinuation of any treatment in 31.3% of patients and of all treatment in 3.3% of patients.
“This large randomized international phase III trial, with a well-designed control arm, provides a high level of evidence for the efficacy of pembrolizumab plus chemotherapy for prolonging survival in the first-line setting – these data will change medical practice. The large survival improvements observed are clearly needed in this vulnerable population who currently are underserved. Cervical cancer has been the ‘poor relation’ in gynae-oncology and in oncology in general, but this study provides further support for immunotherapy as the new cornerstone of its treatment. Whether immunotherapy could be used even earlier in cervical cancer, in localized disease, is an important follow-up question.”
- Expert Opinion
INSIGHTS: Keytruda is already in 2L treatment of cervical cancer, and it is now all set to become a part of SOC in 1L. Adding a PD-1 therapy in 1L will likely reduce the appeal of other PD-1 drugs in the 2L setting, such as Agenus’s balstilimab (anti-PD-1 antibody), which is currently under priority review by FDA and Sanofi’s Libtayo (anti-PD-1), which is eyeing the regulatory submission in 2021. Roche’s Tecentriq, another checkpoint inhibitor, a competitor to Keytruda, is in a similar phase III BEATcc study for 1L setting with March 2023 as the primary completion date. Therefore, Keytruda is expected to lead in the 1L persistent, recurrent or metastatic cervical cancer following its good result.