New data from the pivotal phase 3 Checkmate 214 trial combining ipilumimab and nivolumab presented at the European Society of Medical Oncology (ESMO) conference in Madrid showed superiority for the combination over Sunitinib (Sutent).
The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was more effective in prolonging the lives of newly diagnosed metastatic renal cell carcinoma patients than the current standard of care, sunitinib (Sutent), showing the highest complete response rate (9 percent) ever seen in a phase 3 trial for RCC.
As a result of the positive data, the trial’s Independent Data Monitoring Committee ended the trial prematurely signaling that the combination will likely move forward for approval as a first line treatment in patients with metastatic RCC.
What does this mean for patients?
• For more than a decade now, TKIs have dominated the first line setting in RCC. Most patients are offered either sunitinib or pazopanib for treatment of metastatic disease. If approved, Ipi/Nivo, a combination of two immunotherapy drugs, will likely replace targeted therapies as the treatment of choice, especially given the complete response rates.
• In addition to displacing TKIs as first-line treatment, the combination will also likely make nivolumab as monotherapy in the second line setting obsolete as more patients will undergo combination immunotherapy in the first line.
• Ipilumimab, marketed as Yervoy, has been available for a decade for metastatic melanoma, however it was never approved for RCC, despite efficacy in earlier trials. If the combination is approved, Ipi will now be available in RCC.
• The data showed favorable responses in intermediate and high-risk patients, but low risk patients fared better in the sunitinib arm. Given the high complete response rates will doctors really withhold ipi/nivo from low risk patients? It remains to be seen how patients will be selected.
Many questions are still unanswered, but these results are exciting for RCC patients! We will continue to share updates as this combination moves forward toward approval.