Dr Singer on the Lack of Clinical Benefit for Immunotherapy Rechallenge in Advanced RCC

Adam Singer, MD, PhD, health sciences clinical instructor of medicine, division lead, Kidney Cancer, Division of Hematology/Oncology, University of California Los Angeles Health, discusses data for immunotherapy rechallenge in patients with advanced renal cell carcinoma (RCC) who have experienced disease progression on prior immunotherapy.

Singer notes that data are now available from 2 large phase 3 studies showing a lack of benefit from rechallenging with immunotherapy in patients who have previously been exposed to one of these agents. The first study to assess this approached was the phase 3 CONTACT-03 trial (NCT04338269), which randomly assigned patients with previously treated advanced RCC to receive cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) or cabozantinib alone.

Results presented during the 2023 ASCO Annual Meeting demonstrated no significant difference in progression-free survival (PFS) or overall survival (OS) between the two arms. Patients in the atezolizumab arm experienced a PFS of 10.6 months (95% CI, 9.8-12.3) compared with 10.8 months (95% CI, 10.0-12.5) in those given cabozantinib alone (HR, 1.03; 95% CI, 0.83-1.28; P = .78). The median OS was 25.7 months (95% CI, 21.5–not evaluable [NE]) in the experimental arm vs NE (95% CI, 21.1-NE) in the control arm (HR, 0.94; 95% CI, 0.70-1.27; P = .69).

Similarly, the phase 3TiNivo-2 trial (NCT04987203) randomly assigned patients to receive tivozanib (Fotivda) plus nivolumab (Opdivo) or tivozanib alone. Data presented at the 2024 ESMO Congress showed that the median PFS was 5.7 months (95% CI, 4.0-7.4) for the combination vs 7.4 months (95% CI, 5.6-9.2) for tivozanib alone (HR, 1.10; 95% CI, 0.84-1.43; P = .49).

The findings from these phase 3 trials collectively demonstrate the ineffectiveness of sequential immunotherapy in advanced RCC, highlighting the need for alternative therapeutic strategies, Singer says. He advises that these data should guide clinical decision-making, recommending against the use of immunotherapy after progression on prior immunotherapy due to the lack of benefit and added toxicity, he concludes.