Dr Zhang on the Implications of Findings From the KEYNOTE-564 Trial in RCC

Tian Zhang, MD, MHS, associate professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the implications of findings from subgroup analyses of the phase 3 KEYNOTE-564 trial (NCT03142334) of adjuvant pembrolizumab (Keytruda) in patients with renal cell carcinoma (RCC).

During the 2023 International Kidney Cancer Symposium, Zhang presented results from subgroup analyses examining the application of the KEYNOTE-564 regimen in patients with high-risk RCC. Although all randomized controlled trials evaluate intention-to-treat populations, findings from subgroup analyses of KEYNOTE-564 reaffirm that patients at a heightened risk of RCC recurrence tend to derive greater benefit from pembrolizumab in the adjuvant setting, she states. Engaging in discussions with patients about adjuvant therapy decisions for resected kidney cancer is of paramount importance, Zhang imparts. During these conversations, it is crucial to consider patients’ risk factors and prognostic indicators to weigh the likelihood of recurrence with and without treatment, she adds. Using such data facilitates shared decision making in the clinical setting, according to Zhang.

The safety profile of pembrolizumab remains consistent across KEYNOTE-564 patient subgroups and is characterized by immune-mediated adverse effects similar to those observed in the overall population, Zhang expands. These include rashes, colitis, and less frequently, endocrinopathies, such as thyroiditis and hypothyroidism, alongside mild elevations in liver function and occurrences of pneumonitis, Zhang imparts. Currently, pembrolizumab is being employed in the adjuvant setting, where it is an efficacious treatment option for patients, she says. Pembrolizumab may postpone RCC recurrence and potentially extend patients' overall survival (OS), Zhang notes.

Excitingly, press releases have indicated positive OS outcomes from the KEYNOTE-564 trial, Zhang concludes. Since the presentation of data from the subgroup analyses at the International Kidney Cancer Symposium, additional data from the trial have read out at the 2024 Genitourinary Cancers Symposium and further validate the efficacy of adjuvant pembrolizumab in this context.