The much-awaited late-breaking results of Phase III Checkmate 9ER came out with outstanding outcomes in metastatic 1st line RCC; it evaluated the combination of Cabozantinib/Nivolumab vs. Sunitinib. These impressive results in 651 patients declared that the median PFS has been doubled when compared to Sunitinib, which is 16.6 vs. 8.3m, respectively. The result also evaluated the OS (40% decrease risk of death) & ORR (55.7 vs. 27.1%), with manageable toxicity, efficacy, and tolerability profile with a low rate of treatment-related discontinuations. It was great to hear that the study met both its primary PFS and secondary OS/ORR, demonstrating the superiority of first-line Cabozantinib/Nivolumab vs Sunitinib across key baseline characteristics, including IMDC risk status, tumor PD-L1 expression, and bone metastases.
DelveInsight wonders how this combination will measure up for 1st Line RCC compared to the already existing combinations of Keytruda/Inlyta, Nivolumab/Ipilimumab, Bavencio/Inlyta. The answer lies in the fact that the company is very confident as clinicians are familiar with both these drugs; also, their combination will improve the quality of life at a much greater extent than any other IO-IO or IO-TKI combinations approved so far as it has shown largely superior/statistically significant HRQoL data with Cabozantinib/Nivolumab vs. Sunitinib. Additionally, as claimed previously BMS/Exelixis surpassed the median PFS of its rival Merck’s Keytrua/Inlyta’s median PFS of 15.1 months, taking over the lead again as the combination can be considered a new first-line treatment option.
An excellent presentation was given by Dr. Toni Choueiri, Oncologist at DanaFarber Institute. He gave a background of how science evolved in RCC to eventually design the phase II CheckMate-9ER and underscores the value of collaboration as well as the perseverance to design, enroll, execute, and publish an RCT. Not just that, Dr. Camillo Porta provided a noteworthy analysis at the closure of the session.
Different Industry experts and oncologists have presented their views on the same:
“We already have data for I/O plus TKI for front line kidney cancer (Pembro + Axitnib and Avelumab + Axitinib) is this setting. The winner in that space will probably be the one with less toxicity and which TKI is easy to obtain in the clinic. Good to have options.”
Some of them were also skeptical about the preference of IO-IO or IO- TKI combinations by the clinicians: “The medical community is divided about whether two immunotherapies or immunotherapy plus an anti-angiogenic drug is the better choice since the different combinations appear to have similar effectiveness”.
While few were also intrigued about the exclusion of non-clear cell carcinoma patients: “The 18 months of follow-up is still quite short. The question is whether the responses to treatment are durable or patient’s progress at some point. It would also be useful to learn whether the combination of cabozantinib and nivolumab is effective in non-clear cell carcinoma. This is a minority of patients with advanced kidney cancer which are not well studied and were excluded from this trial”
The key opinion leaders also discussed regarding the switching of therapies: “If you start with a combination of immune therapy only, it becomes an automatic choice to use an anti-angiogenic drug in the second line. But if you begin with a combination of two mechanisms of action, such as immune therapy and an anti-angiogenic drug, then the second-line choice is less clear. More data are needed on the most suitable order of therapy for the entire population as well as specific groups such as high tumor burden versus slow-growing disease,”
For deep diving, DelveInsight’s Advanced Renal Cell Carcinoma (RCC) - Market Insights, Epidemiology, and Market Forecast-2030 will provide an in-depth market analysis and market forecast, including all the recent and relevant insights incorporated till ESMO 2020.