Adjuvant pembrolizumab improves overall survival (reduced mortality by 38%). We need to make sure that urologists are also aware so those patients with a high risk of recurrence can get this medication.
Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point.
A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P=0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.
Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.)
This is helpful when we get patients who have a renal mass as this may help distinguish between benign vs malignant.
Belzutifan beat everolimus in progression-free survival (PFS) and response rate, but hardly anyone uses it alone, mostly used in combination with Lenvatinib.
It is yet another option for renal cell cancer patients.
An intriguing study from the UK, patients had 24 weeks of sunitinib or pazopanib followed by a continuation or treatment holiday. Non-inferiority could not be established, but there was seemingly no meaningful reduction in OS (28 vs. 27 months overall), with a noticeable improvement in toxicity in the treatment break group. This may be a realistic strategy for patients with a focus on QOL or cost-effectiveness.
Pembrolizumab remains the only adjuvant option for high risk RCC after curative surgery. The OS curves seem to be beginning to separate and hope to be positive with longer f/u. The ongoing Durvalumab + Tremilumumab will be an interesting adjuvant study for RCC when the results are available.
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