Beyond Surgery: The Evolving Landscape of Adjuvant Therapy in Kidney Cancer

Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, dove into the complexities of adjuvant therapy for kidney cancer, providing valuable insights for oncology clinicians in the latest episode of Oncology Decoded. The discussion began with a fundamental overview of adjuvant therapy, which aims to eradicate residual microscopic disease and mitigate the risk of cancer recurrence.

Bupathi, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Garmezy, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRIand medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, underscored the curative potential of adjuvant therapy in kidney cancer.

The discussion also focused on 2 primary modalities of adjuvant therapy: targeted therapies and immunotherapy. Targeted therapies, particularly VEGF tyrosine kinase inhibitors, were discussed in the context of clear cell kidney cancer, the predominant subtype, where they inhibit the VEGF signaling pathway to impede cancer cell growth.

Bupathi and Garmezy spoke about results from the phase 3 KEYNOTE-564 trial (NCT03142334), which led to the FDA approval of pembrolizumab (Keytruda) for high-risk clear cell kidney cancer.^1,2 The positive results from this trial are superior to those from others that explored different immunotherapy agents and regimens, none of which demonstrated a similar benefit. It was noted that there are differences in interpretations, heterogeneity in study designs, and patient populations for each trial.

Regarding risk stratification in the postnephrectomy setting, the hosts gave a critical evaluation of the role of nomograms in predicting recurrence. The benefits of adjuvant therapy against the potential for treatment-related toxicities were weighed, with an emphasis on the importance of individualized patient counseling.

Finally, they highlighted the management of disease progression following adjuvant pembrolizumab, with a focus on treatment sequencing and the role of second-line therapies. The relevance of extrapolating data from metastatic trials to the adjuvant setting was discussed, with a pragmatic approach to clinical decision-making.

References

1. Choueiri TK, Tomczak P, Park SH, et al; KEYNOTE-564 Investigators. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa2312695
2. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. News release. FDA. November 17, 2021. Accessed April 24, 2025. https://tinyurl.com/yzxcjetz