Eric A. Singer, MD, professor, Urology and Bioethics, director, the Division of Urologic Oncology, The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center (OSUCC)–James, discusses the safety of perioperative nivolumab (Opdivo) and cabozantinib (Cabometyx) in patients with metastatic clear cell renal cell carcinoma (RCC).

After the combination demonstrated efficacy and safety in the frontline treatment of patients with advanced RCC during the phase 3 CheckMate 9ER trial (NCT03141177), Singer and colleagues investigated the use of nivolumab plus cabozantinib prior to cytoreductive nephrectomy in patients with metastatic clear cell RCC in the phase 2 Cyto-KIK trial (NCT04322955). Patients received 40 mg of cabozantinib per day and 480 mg of nivolumab once every 4 weeks for 12 weeks prior to surgery.

The goal of Cyto-KIK is to examine the safety and efficacy of pretreating patients with the combination before continuing it following surgery, Singer says. The primary end point of the trial is complete response rate, which differs from many other studies conducted in this setting for patients with RCC, Singer expands.

The safety of the regimen and the optimal time to stop treatment with cabozantinib prior to surgery was previously unknown, Singer says. Investigators used a rolling 3+3 design to examine different stoppage points for cabozantinib, starting with 3 weeks prior to surgery, then 2 weeks prior to surgery. No issues were observed when cabozantinib was held 3 weeks or 2 weeks prior to surgery, Singer explains.

Furthermore, in findings presented at the 2023 American Urological Association Annual Meeting, the immuno-oncology–TKI combination with cabozantinib held 2 weeks prior to surgery was safe in a presurgical setting. No treatment-related adverse effects were reported during or after surgery, and no patients required delays in resuming treatment with the doublet after surgery, Singer concludes.

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Eric A. Singer, MD, discusses the safety of perioperative nivolumab and cabozantinib in patients with metastatic clear cell renal cell carcinoma.


Dr Singer on the Safety of Perioperative Nivolumab and Cabozantinib in RCC

Eric A. Singer, MD, professor of Urology and Bioethics, director, Division of Urologic Oncology, The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center–James, discusses the use of systemic pembrolizumab (Keytruda) monotherapy in patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC).

The phase 2 KEYNOTE-057 trial (NCT02625961) was designed to evaluate the use of single-agent pembrolizumab in 2 cohorts of patients with high-risk BCG-unresponsive NMIBC, Singer says. Cohort A consisted of patients with carcinoma in situ (CIS) with or without papillary tumors, and cohort B included those with non-CIS papillary tumors. Patients in both cohorts were previously treated with 2 induction courses of BCG and were either ineligible for, or declined to undergo, radical cystectomy, Singer says. Pembrolizumab was delivered intravenously to provide systemic effects, Singer adds. The study's primary end point was a disease-free survival (DFS) rate greater than 20%.

Previously reported results from cohort A showed that the clinical CR rate with pembrolizumab in cohort A was 41% at 3 months, with a median duration of 16.2 months. In January 2020, the FDA approved pembrolizumab for use in this population according to these findings.

Data from cohort B were presented at the 2023 AUA Annual Meeting. In this cohort of 132 patients, pembrolizumab monotherapy produced a 12-month DFS rate of 43.5% at a median follow-up of 45.4 months, Singer reports. The median DFS was 7.7 months. Although 27% of patients subsequently underwent radical cystectomy, many other patients were able to avoid or considerably delay this procedure, Singer notes.

These data suggest that systemic pembrolizumab monotherapy is another viable option for patients with recurrent high-grade NMIBC who have progressed on BCG, Singer concludes.

Eric A. Singer, MD, discusses the use of systemic pembrolizumab monotherapy in patients with Bacillus Calmette-Guérin–unresponsive, high-risk non–muscle invasive bladder cancer.

Eric A. Singer, MD

Articles

Dr Singer on the Safety of Perioperative Nivolumab and Cabozantinib in RCC

Dr Singer on Systemic Pembrolizumab Monotherapy in BCG-unresponsive High-Risk NMIBC