Repeat immune checkpoint inhibitor therapy not recommended for aRCC

Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

TiNivo-2 was presented for the first time here at ESMO 2024 in beautiful Barcelona. It was a phase III study to address an important question in immunology and in the field of immune checkpoint inhibitors in renal cell cancer, but I believe it applies to other solid tumours, whether re-challenge with a PD-1/PD-L1 inhibitor after prior progression on PD-1/PD-L1 inhibitor has merit. We see that practice all over the world. Folks, in many occasions, even after progression, they keep their checkpoint inhibitor going with each regimen. We had a study last year with atezolizumab, and the control arm was cabozantinib. That CONTACT-03, that was really negative for all the primary endpoints.

Here, TiNivo-2 addressed the same question, but with two major differences. One is that we did not use a PD-L1 inhibitor. We used a PD-1 inhibitor, nivolumab. Second, the patient, one third of patients, their last drug was not a PD-1 inhibitor. Patients were randomised to tivozanib versus tivozanib plus nivolumab, and after a median follow-up close to a year, the progression-free survival was not significant in either arm. The hazard ratio was over 1. Of note, the dose of tivozanib was lower in the combination because of the risk of grade 3/4 hypertension. The toxicity was similar. Not just the progression-free survival endpoint was not met, but neither the response rate, similar in both arms, or the overall survival.

This is the second phase III trial, I would say in solid-tumour but here let’s focus on renal cell cancer, that asked that question of rechallenge after prior progression, and it’s dead negative. I think this practice, in general, should be discouraged, and heavily discouraged. There are some exceptions, but in general it should be discouraged.