Pembrolizumab after surgery shows ‘practice changing’ survival benefit for kidney cancer
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Key takeaways:
- First phase 3 study to show a survival benefit with adjuvant therapy in kidney cancer.
- Adjuvant pembrolizumab improved treatment outcomes across various subgroups.
Adjuvant therapy with pembrolizumab following nephrectomy conferred significant improvement in OS compared with placebo among adults with renal cell carcinoma who had a high risk for disease recurrence, study results showed.
Updated data from the phase 3 KEYNOTE-564 trial revealed that adjuvant pembrolizumab (Keytruda, Merck) after surgery reduced the risk for death by 38% compared with placebo.
The findings — presented at ASCO Genitourinary Cancers Symposium — support the use of adjuvant pembrolizumab as a standard of care for this patient population, according to study investigators.
“Through this study, we now understand that pembrolizumab is more than just a measure to delay recurrence in kidney cancer; it is a means to significantly improve overall survival for patients,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, said in an ASCO press release. “Considering that many patients with clear cell renal cell carcinoma have a high risk [for] recurrence leading to noncurable distant metastases, this finding is practice changing.”
Background and methodology
Prior data from the double-blind KEYNOTE-564 trial showed an improvement in DFS compared with placebo following nephrectomy in patients with clear cell renal cell carcinoma who are at an increased risk for recurrence.
Researchers conducted a follow-up analysis presented at ASCO GU to also report OS data.
The trial included 994 adults with histologically confirmed clear cell renal cell carcinoma either with or without sarcomatoid features that have an increased risk for recurrence, an ECOG PS of 0 or 1, nephrectomy and/or metastasectomy of no more than 12 weeks before randomization and no prior systemic therapy for renal cell carcinoma.
Researchers randomly assigned patients in a 1:1 ratio to receive 200 mg IV pembrolizumab (n = 496) or placebo (n = 498) every 3 weeks for at least 17 cycles, or until disease recurrence, intolerable toxicity or withdrawal of consent.
DFS served as the study’s primary endpoint, with OS included as a key secondary endpoint.
Results, next steps
Researchers noted an improvement in OS with pembrolizumab compared with placebo (median OS not yet reached; HR = 0.62; 95% CI, 0.44-0.87).
Fifty-five total OS events occurred in the investigative arm, while 86 occurred in the placebo arm; researchers reported an estimated OS rate at 48 months of 91.2% for patients treated with pembrolizumab and 86% for those who received placebo.
Researchers also noted OS improvements across subgroups treated with pembrolizumab, including patients with M0 disease (HR = 0.63; 95% CI, 0.44-0.9), M1-NED disease (HR = 0.51; 95% CI, 0.15-1.75), a PD-L1 combined positive score (CPS) less than 1 (HR = 0.65; 95% CI, 0.31-1.38), or a CPS of 1 or greater (HR = 0.62; 95% CI, 0.42-0.91). The increase in OS also extended to patients with sarcomatoid features (HR = 0.69; 95% CI, 0.28-1.7) or without sarcomatoid features (HR = 0.57; 95% CI, 0.39-0.84).
Study investigators also observed a similar DFS benefit comparable to a prior interim analysis (HR = 0.72; 95% CI, 0.59-0.87).
“For patients with renal cell carcinoma, up to 40% may experience recurrence following surgery, at which point there is a significantly lower chance of survival,” Choueiri said in a Merck press release. “Results from KEYNOTE-564 show that pembrolizumab as adjuvant therapy significantly improved overall survival by 38% compared to placebo, becoming the first ever phase 3 adjuvant trial to show improved survival for renal cancer patients at risk [for] recurrence after surgery.”
References:
- ASCO. New study shows survival benefit with adjuvant therapy in patients with renal-cell kidney cancer for the first time (press release). Available at: https://old-prod.asco.org/about-asco/press-center/news-releases/new-study-shows-survival-benefit-adjuvant-therapy-patients. Posted Jan. 27, 2024. Accessed Feb. 1, 2024.
- Choueiri TK, et al. LBA 359. Presented at: ASCO Genitourinary Cancers Symposium; Jan. 25-27, 2024; San Francisco.
- Merck. Merck’s Keytruda (pembrolizumab) reduced the risk of death by 38% versus placebo as adjuvant therapy for patients with renal cell carcinoma (RCC) at an increased of recurrence following nephrectomy (press release). Available at: https://www.merck.com/news/mercks-keytruda-pembrolizumab-reduced-the-risk-of-death-by-38-versus-placebo-as-adjuvant-therapy-for-patients-with-renal-cell-carcinoma-rcc-at-an-increased-risk-of-recurrence-follow/. Posted Jan. 27, 2024. Accessed Feb. 1, 2024.
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Choueiri TK, et al. LBA359. Presented at: ASCO Genitourinary Cancers Symposium; Jan. 25-27, 2024; San Francisco.
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