Repeat immune checkpoint inhibitor therapy not recommended for aRCC

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Published: 14 Sep 2024
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Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

Dr Toni Choueiri speaks to ecancer at ESMO 2024 about the results from the phase III TiNivo-2 study which evaluated tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma following 1 or 2 prior therapies including an immune checkpoint inhibitor.

He reports that the addition of nivolumab, a PD-1 inhibitor, to tivozanib did not delay the progression of cancer, nor improve overall survival or response rates compared to tivozanib monotherapy.

This leads to the conclusion that repeat immune checkpoint inhibitor therapy should be discouraged in patients with advanced renal cell carcinoma.

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.