Toni K. Choueiri, MD
The potential practice-changing CABOSUN findings presented at the 2017 ESMO Congress validated the investigator-assessed results the oncology community learned of more than 1 year prior. With an independent review, frontline treatment with cabozantinib (Cabometyx) was found to demonstrate superiority in progression-free survival (PFS) over sunitinib in patients with advanced renal cell carcinoma (RCC).
Specifically, findings showed that cabozantinib-treated patients had a median PFS of 8.6 months versus 5.3 months for patients treated initially with sunitinib, representing a 52% reduction in the hazard for progression or death.
The independent review of the data confirmed the primary analysis of the CABOSUN randomized trial, which showed a median PFS of 8.2 months with cabozantinib and 5.6 months with sunitinib by investigator assessment (HR, 0.66; 95% CI, 46%-95%; 1-sided P
Additionally, an updated review of overall survival (OS) did show a numerical advantage in favor of cabozantinib, but the difference did not achieve statistical significance. This was also consistent with the initial investigator review of survival.
In an interview with OncLive during the 2017 ESMO Congress, Toni K. Choueiri, MD, director of the Kidney Cancer Center at Dana-Farber Cancer Institute, shed light on the excitement surrounding the CABOSUN and CheckMate-214 trials, and why the future of the RCC field lies in novel combination regimens.
OncLive: Could you recap the main findings from the CABOSUN trial?
At the 2016 ESMO Congress, we presented CABOSUN results in the plenary session and we showed that, for the first time, a VEGF tyrosine kinase inhibitor (TKI) had antitumor activity, and it did provide superior PFS over sunitinib in metastatic RCC of intermediate and poor risk. The analysis was investigator-assessed, so what we did this time is provide an independent review with more follow-up for OS and [investigated] MET as a biomarker in the study.
Like the investigator assessment, we had similar findings in the independent review and the median PFS was not different. The hazard ratio was even lower, around 0.48, with cabozantinib providing superior PFS compared with sunitinib. The responses were double with cabozantinib. This study was not powered for OS benefit, but the OS also was trending in the right direction. The updated toxicity profile data from both drugs were not different between both arms.
How do you see these findings shaking up the standard of care for patients with RCC?
There is potential for cabozantinib to be an option in the frontline setting. Currently, this drug is approved in patients who progress after VEGF TKI, anti-VEGF therapy, or antiangiogenic therapy. Although CABOSUN is still a randomized phase II and not phase III study, you have a study that showed, by both investigator and by independent review, superiority for the primary endpoint of PFS. It could become an option in intermediate- and poor-risk patients that are systemic therapy–naïve.
What are the next steps? Will a phase III trial be required to submit for frontline approval?
This is a good question. I don't know. There are other examples, such as the lenvatinib (Lenvima)/everolimus (Afinitor) combination, which was approved in the second-line setting based on phase II data. That was for a drug that was new to the field, where here you have a drug that already is used in the second-line setting, so I don’t know if they will require a phase III trial. The [independent] center review is likely required and that was done, which was what we presented at the 2017 ESMO Congress.
We also saw subgroup analyses of the METEOR trial at this meeting. What are the data coming out from that?
For the past year, we have been presenting a subgroup analysis of patients with prior nephrectomy. We looked at patients who had their first TKI, whether pazopanib (Votrient) or sunitinib. An interesting analysis was presented by Dr Thomas Powles and looked at patients who progressed on prior immune checkpoint blockers, received cabozantinib, and the effect was even more pronounced. We also presented the quality of life (QOL) metrics from METEOR that showed a somewhat similar QOL profile compared with everolimus.
Can you comment on the data from CheckMate-214, another pivotal trial presented at this meeting?
This is big news in the field. For the first time in the frontline setting, an immunotherapy combination had 2 of the 3 coprimary endpoints met. Responses were higher than sunitinib, and we just realized that even the OS was in favor of the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) and a lot of things need to be taken into consideration.