ESMO 2024: Metastatic Kidney Cancer Should Not be Re-Treated with Immunotherapy

People with metastatic kidney cancer who already received one or two lines of treatment that included immunotherapy did not fare better when offered an additional round of immunotherapy after their cancer progressed.

The results from the phase 3 TiNivo-2 trial, presented at the recent European Society of Medical Oncology (ESMO) meeting in Barcelona, Spain, compared combination treatment with the targeted kinase inhibitor tivozanib plus the immunotherapy nivolumab against tivozanib alone, suggesting this type of treatment sequence is not a useful strategy in metastatic kidney cancer patients. [ESMO 2024, Abstract LBA73]

The TiNivo-2 study was also published in the journal The Lancet.

Primary investigator Dr. Toni Choueiri of the Dana-Farber Cancer Institute, said: “What remains unknown, in large part, is the optimal sequence [of RCC treatments] in patients whose disease has progressed after treatment with an immune checkpoint inhibitor (ICI). If we rechallenge with the same or a different ICI, does this improve clinical outcomes? Could outcomes be impacted if we use a non-ICI drug before ICI rechallenge and an ICI break? What about using a PD-1 vs PD-L1 inhibitor, does that matter?” 

TiNivo-2 included 343 metastatic kidney cancer patients who had been treated with immunotherapy before. Participants were randomly assigned to tivozanib plus nivolumab or tivozanib alone and followed up for an average of 1 year. Average progression-free survival (PFS) was not significantly different between the groups – 5.7 months in the combination arm vs 7.4 months in the tivozanib arm.

If a participant’s immediate previous therapy included immunotherapy, PFS was slightly better in both arms, favoring the combination arm. However, if targeted therapy was the most immediate previous therapy, there was no PFS difference between the groups. Both groups reported a similar number of serious side effects.

Choueiri said the results confirm the key conclusions from an earlier study – the phase 3 CONTACT-03 study – which similarly compared a targeted therapy plus immunotherapy combination (cabozantinib plus atezolizumab) with targeted therapy alone (cabozantinib) in RCC patients whose cancer progressed after prior immunotherapy treatment and found the addition of immunotherapy did not positively impact patient outcomes.

“I believe [the TiNivo-2 data] debunk the theory that break and rechallenge is better,” Choueiri said.

The TiNivo-2 results do support tivozanib alone as a second-line treatment option following progression after immunotherapy, Choueiri said.

Dr. Manuela Schmidinger of the Medical University of Vienna, a discussant who was not involved in the TiNivo-2 trial, pointed out that the dose of tivozanib in the combination arm – reduced to 50% of the normal dose as part of the trial design to prevent toxicity – could indicate that adding nivolumab was unable to overcome the disadvantage of an underdosed tivozanib regimen compared to the normal dose.

The question of how to best sequence treatments in metastatic kidney cancer patients remains open, she said.