The initial results of the CheckMate-9ER trial were presented first at ESMO 2020 in a Presidential Symposium as part of the main ESMO programme. These results demonstrated benefits with the combination of Cabometyx and Opdivo across efficacy endpoints in a representative population inclusive of all [?? 0:22] groups. These included median progression free survival, the primary endpoint, which was double with the combination versus sunitinib – 16.6 months versus 8.3 months; an increase in overall survival demonstrated in a 30% reduction in the risk of death when patients were treated with the combination; and objective response rates which were 56% versus 27%
respectively as well as a longer duration response with a tolerable safety profile.
Further data were subsequently presented at the ASCO GU conference in 2021. At a median follow-up of two years we demonstrated that this efficacy benefit was sustained with longer follow-up. In addition, these data were reinforced by new health-related quality of life data which demonstrated that patients treated with the combination of cabozantinib nivolumab reported significantly improved quality of life versus sunitinib.
What new data are you presenting this year?
The new data to be presented at ASCO GU 2022 focussed on updated results from the pivotal CheckMate-9ER phase III study evaluating cabozantinib in combination with nivolumab in previously untreated advanced renal cell carcinoma being announced this Saturday.
The key takeaways from the ASCO GU 2022 data are a continued efficacy and tumour shrinkage benefit with Cabometyx in combination with Opdivo compared to sunitinib in the first line of advanced renal cell carcinoma. The final overall survival analysis data were presented at the ASCO GU conference with a median follow-up of 32.9 months. This new data demonstrated that cabozantinib in combination with nivolumab continued to show superiority compared to sunitinib across all the efficacy endpoints evaluated, including overall survival, progression free survival, objective response rate and disease control rate, including increased complete responses.
This analysis confirms a continued improvement in the secondary endpoint of overall survival with a 30% reduction in the risk of death when patients were treated with the combination. Significant improvements in both progression free survival and objective response rate were shown to be sustained with the combination within this extended follow-up analysis with a median PFS of 16.6 months versus 8.3 months as well as an overall response rate of 55.7% compared to 28.4%.
Importantly, the complete response rate for the combination, which is something that we know has a relation with the overall survival, was shown to increase with extended follow-up with 12.5% of patients achieving a complete response with the combination compared with 5.2% for sunitinib.
What did you see in terms of adverse events?
The safety profile identified in the CheckMate-9ER trial was consistent with that previously reported and observed with cabozantinib and nivolumab and no new safety signals emerged in this extended follow-up.
How could these findings impact clinical practice?
That’s important because for people living with advanced renal cell carcinoma the current survival rate is around 12%. So there has been a dramatic evolution in the treatment landscape across lines of therapy for people living with renal cell carcinoma over recent years. So this is an exciting time to be a treating physician in this area.
These new data show there is a possibility we can offer patients for their advanced disease, presenting the opportunity to live longer and some patients even achieve a complete response with maintaining their quality of life. While length of survival should be the priority focus on this issue and should account for maximum efficacy, of course, patient interventions which may constitute a significant impact of a person’s quality of life should also be considered.
These complementary presentations underscore the growing need for treatments which provide a strength of efficacy with maintaining quality of life for the patients as we are starting to see a trend of people living longer with cancer.
What did you find in the health-related quality of life data that is also being presented?
In a separate analysis with 32.9 months median follow-up patients continued to report clinically meaningful quality of life benefits with the combination of cabozantinib plus nivolumab as compared to sunitinib. These exploratory outcomes were measured using the Functional Assessment Of Cancer Therapy Kidney Symptoms Index 19 which assessed quality of life associated specifically to kidney cancer as well as the EQ-5D-3L instrument which assessed quality of life more generally.
Quality of life scores from these instruments were found to be improved or maintained over the time amongst patients treated with the combination while reductions in scores were observed with sunitinib. Additionally, those who received the combination were 48% less likely to be notably bothered by treatment side effects than patients in the sunitinib arm.
So this updated data followed the publication of 23.5 months median follow-up quality data are published in the Lancet Oncology from January 2022.
