Adjuvant treatment is predicated on the hope that treatment of micrometastatic disease is effective and potentially curative. Two phase III studies were reported in the last year. Neither demonstrated improved overall survival; however, S-TRAC did show improvement in progression-free survival.
Checkmate 025 randomized patients with advanced RCC, clear cell component 1:1 to nivolumab versus everolimus. The primary endpoint was overall survival (OS). Patients in the nivolumab arm had median OS of 25.0 months (95% CI 12.5-NE) versus 19.6 months (95% CI 17.6-23.1) for patients receiving everolimus. The hazard ratio for overall survival favored the nivolumab group (HR 0.73, 95% CI 0.57-0.93, p = 0.0018). Nineteen (total n = 406) patients had grade 3/4 adverse events.
The METEOR trial randomized patients with advanced RCC, clear cell component 1:1 to cabozantinib versus everolimus. The primary endpoint was progression-free survival (PFS). Median PFS for cabozantinib was 7.4 months compared to 3.9 months for everolimus (HR 0.51, 95% CI 0.41-0.62, p < 0.0001 favoring cabozantinib). Overall survival was 21.4 months (95% CI 18.7-NE) for cabozantinib versus 16.5 months (95% CI 14.7-18.8) with a hazard ratio for OS favoring cabozantinib (HR 0.66, 95% CI 0.53-0.83, p = 0.003). Grade 3/4 adverse events occurred in 71% of patients on cabozantinib versus 60% on everolimus.
A first-in-class small molecule antagonist of HIF2α (PT2399) was reported within the past year and was shown to inhibit the clear cell RCC cell line 786-O in vitro and through an in vivo mouse model. Further, in these models, PT2399 performed better than sunitinib and was better tolerated. Human trials are eagerly awaited.
Speaker: James Brugarolas, MD, PhD, The University of Texas Southwestern Medical Center
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA