Dr Tan on the Selection of IO-Based Combination Regimens in Advanced RCC

Alan Tan, MD, genitourinary oncology and melanoma specialist, Vanderbilt-Ingram Cancer Center; associate professor, medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, discusses long-term data guiding the selection of immuno-oncology (IO)–based combination regimens in advanced renal cell carcinoma (RCC).

Eight-year follow-up data from the phase 3 CheckMate 214 trial (NCT02231749) evaluated nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with intermediate- or poor-risk RCC, and continues to show efficacy, Tan begins. Importantly, the Kaplan-Meier overall survival (OS) curves with this IO combination have now crossed and surpassed those of IO-TKI combinations in favorable-risk populations, he reports. For patients with favorable-risk disease treated with nivolumab plus ipilimumab, the hazard ratio (HR) is now 0.82, which is superior to HRs historically reported in IO-TKI trials. This suggests that the IO-IO combination may now be a viable treatment option for patients in this risk category as well, not just those with intermediate or poor risk, Tan explains.

Deciding between an IO-IO vs IO-TKI regimen often comes down to clinical presentation, Tan continues. Patients with high disease burden or more aggressive symptoms, such as pleural effusions, malignant ascites, or overall poor physical condition, often benefit more from an IO-TKI combination because they need a rapid response to stabilize their condition, he explains. The IO-TKI combinations have shown long-term survival benefits extending up to 5 years in these patients, although maintaining disease control off treatment in this group can be more challenging, Tan notes.

For patients treated with nivolumab and ipilimumab, 35.1% were alive at 90 months, with some still off therapy and potentially cured, Tan says. Although longer follow-up is needed to confirm whether these patients are truly cured, this dataset has the longest follow-up for an immunotherapy doublet regimen in RCC, and it sets the stage for future advances in combination therapies, Tan concludes.