Dr Chitkara on Outcomes With IO Doublet Therapy in ccRCC by Disease Subtype

“We know that patients [with] sarcomatoid [disease] might respond worse to immunotherapy compared with those [with] rhabdoid [disease]. It would be helpful if clinical trials prospectively have this subgroup analysis built in [so we can] understand how the patients are responding in different subgroups.”

Akshit Chitkara, MD, a hematology-oncology fellow at Sidney Kimmel Comprehensive Cancer Center at Jefferson Health, discussed findings from a retrospective study of outcomes with frontline nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with metastatic clear cell renal cell carcinoma (ccRCC).

The study enrolled 514 patients with ccRCC and subdivided them by sarcomatoid dedifferentiation only, rhabdoid dedifferentiation only, both sarcomatoid and rhabdoid dedifferentiation, grade 4 nonsarcomatoid/nonrhabdoid disease, and unknown histologic subtype. Patients with grade 3 or lower disease were also included as the reference group.

Findings from the study, which were presented during the OncLive National Fellows Forum on Genitourinary Cancer prior to the 2026 Genitourinary Cancers Symposium, demonstrated that patients with grade 3 or higher disease (n = 197) experienced a median overall survival (OS) of 5.4 months (95% CI, 4.5-7.7), a 5-year OS rate of 53% (95% CI, 43%-61%), a median time to next treatment (TTNT) of 12 months (95% CI, 9-18), and a 1-year TTNT rate of 49% (95% CI, 42%-56%). Among patients with sarcomatoid-only disease (n = 61), these respective values were 2.9 months (95% CI, 2.0-3.8), 31% (95% CI, 18%-45%), 11 months (95% CI, 6-18), and 49% (95% CI, 36%-61%). In the rhabdoid-only disease group (n = 67), the median OS, 5-year OS rate, median TTNT, and 1-year TTNT rate were not reached (NR; 95% CI, 3.2-NR), 59% (95% CI, 45%-71%), 8 months (95% CI, 6-31), and 43% (95% CI, 31%-55%), respectively.

Chitkara noted the substantial variation in how pathology findings are reported and how disease is grade across institutions. However, he underscored that potential outcomes by sarcomatoid and rhabdoid dedifferentiation are often not shared. The results of this retrospective study emphasize the need for oncologists to be aware of the precise histological subtype of a patient’s disease prior to treatment in order to select the best treatment option for them, he concluded.