Nivolumab is currently licensed in the UK for the treatment of locally advanced or metastatic squamous non-small cell lung cancer after prior chemotherapy in adults (Nivolumab BMS) and for the treatment of advanced (unresectable or metastatic) melanoma in adults (Opdivo). It has been granted ‘breakthrough therapy’ status in the US for the treatment of advanced renal cell carcinoma, based on the results of this study (CheckMate-025). The trial was stopped early after an analysis showed that it significantly improved overall survival vs. everolimus.
This study has been published alongside a Phase III trial of another new agent in renal cell carcinoma - cabozantinib, a multikinase inhibitor which targets VEGFR, MET, RET, and AXL9. The authors of a related editorial say the benefit of both of these agents, as compared with everolimus, is ‘unequivocal’.
They note however that there was a very low rate of complete remission seen in the studies (0% with cabozantinib and 1% with nivolumab). It is possible that this may be unnecessary to achieve a long-term benefit, but may suggest that selection or combination approaches may expand the benefit spectrum.
The authors of the editorial suggest that nivolumab is the choice for patients who have disease progression while they are receiving VEGF-targeted therapy, with its demonstrated improvement in overall survival compared with everolimus. Cabozantinib improved progression-free survival but the interim analysis of overall survival (secondary endpoint) was not statistically significant; in addition there were significant side effects necessitating dose reduction in 60% or more of patients. They therefore suggest that this would be a salvage treatment option, and would compete with other VEGFR inhibitors as third-line or later therapy.