Dr. Zhang on the Selection of Immunotherapy-Based Regimens in Metastatic RCC

Tian Zhang, MD, MHS, associate professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the selection of first-line immunotherapy-based treatments for patients with metastatic renal cell carcinoma (RCC).

Clinicians must weigh several patient and disease characteristics when choosing between an immunotherapy-based regimen vs a VEGF inhibitor and immunotherapy combination for the treatment of patients with RCC, Zhang begins. The standard immuno-oncology (IO) doublet in this space is ipilimumab (Yervoy) and nivolumab (Opdivo), Zhang says, noting that VEGF/IO regimens include axitinib (Inlyta) and pembrolizumab (Keytruda) or lenvatinib (Lenvima) and pembrolizumab.

Recent data from the 5-year survival analysis of the phase 3 KEYNOTE-426 trial (NCT02853331) demonstrated the superior efficacy of first-line pembrolizumab and axitinib over treatment consisting of sunitinib (Sutent) monotherapy in patients with newly diagnosed, treatment-naïve stage IV clear cell RCC, Zhang reports. Similarly, the 4-year survival results from the phase 3 CLEAR trial (NCT02811861) underscored the survival advantage associated with lenvatinib plus pembrolizumab vs sunitinib in participants with advanced renal cell carcinoma, she details. Importantly, these regimens have shown early disease control marked by improvements in progression-free survival, Zhang notes.

Based on these data, a VEGF/IO combination such as axitinib with pembrolizumab may provide more benefit for patients presenting with symptomatic or de novo metastatic disease, which necessitates early disease control, Zhang states. Conversely, patients with less symptomatic disease and lower tumor burdens may be better candidates for an ipilimumab and nivolumab doublet, Zhang says. This approach is also a viable option for patients aiming to achieve a complete response with treatment, as well as those concerned about the long-term toxicities associated with VEGF inhibitors, she adds.

Ultimately, the choice of therapy in the frontline setting should be a collaborative decision between clinicians and patients, considering individual disease characteristics and treatment goals.