Cabozantinib Following IO Therapy Failure Confirmed Safe, Feasible in Metastatic RCC

In patients with advanced metastatic renal cell carcinoma (mRCC), treatment with cabozantinib (Cabometyx) directly after immunotherapy (IO) combinations was deemed safe and feasible, with no new safety signals, according to data presented at the 2022 ASCO Genitourinary Cancers Symposium.

Viktor Grüwald, MD, PhD, who presented the findings and professor of interdisciplinary genitourinary oncology at the University Hospital in Essen, Germany, explained that these data are similar to prior data, such as from the METEOR study (NCT01865747) from 2016, and confirm the use of cabozantinib in this setting.

“I think what we have seen is that it’s quite confirming that even … our real-world population was really coming close to the efficacy data that we have seen in the METEOR study, and that’s something that I think is quite compelling in terms of the role of cabozantinib after the failure of immuno agents. And because there is just scarce data, I think it is important to see that the recommendations that we gave in guidelines are quite supported. They’re supported by our data actually,” he said in an interview with Targeted Oncology™’s sister publication CURE®.

Grünwald explained that data on cabozantinib after IO combinations in mRCC still remains scarce, so he and researchers further evaluated the safety and efficacy of cabozantinib after IO-based therapy with a primary endpoint of the incidence of serious adverse events (SAE).

With a cutoff date of October 8, 2021, the final analysis included 56 eligible patients (71.4% male) with a median age of 66 years. There were 87.5% of patients (n = 49) who had a nephrectomy, 66.1% (n = 37) had clear cell RCC and 89.3% (n = 50) had 2 or more previous lines of therapy.

The usual dosing of cabozantinib is 60 mg, and 62.5% (n = 35) of patients started at a reduced dose at the start of treatment, 55.4% (n = 31) required a dose reduction during treatment and 1.8% (n = 1) discontinued treatment during this study. The median treatment duration was 6.1 months. During this time, 10.7% (n = 6) of patients had a partial response, 19.6% (n = 11) had stable disease and12.5% (n = 7) had progressive disease.

Overall survival (OS) and progression-free survival (PFS) were assessed from the start of therapy, and researchers compared these data with 20 patients who had a starting dose of 60 mg (cohort A) to those receiving less than 60 mg (cohort B) in a post-hoc analysis.

Results demonstrated the median OS and PFS of 15.34 months (95% CI; 8.94, 20.93) and 6.34 months (95% CI, 5.29-8.25) in the intention-to-treat population, respectively. In addition, median OS and PFS in cohort A were 10.48 months (95% CI, 6.01-34.14) and 6.51 months (95% CI, 2.99-10.87. In cohort B, median OS and PFS were 16.46 months (95% CI, 9.56-23.33) and 6.34 months (95% CI, 4.86-8.71).

“The data that we generated is clinically meaningful because it is a common practice and our data supports the current clinical practice,” Grünwald added. “… I think it reassures the role of cabozantinib. Something that it brings up is the role of the dose of cabozantinib, of course, and as it appears, even in the METEOR study, about half of the patients needed some dose reductions and the median dose was about 40 milligrams. So at the end of the day, I think 40 milligrams is a good starting point for cabozantinib.”

Additionally, those who started on the lower dose experienced fewer side effects compared to those who started on 60 mg. All grade AEs and grade 3-5 AEs occurred in 87.5% (n = 49) of patients and 44.6% (n = 25) in ITT. In cohort A, all-grade AEs and grade 3-5 AEs occurred in 95% (n = 19) of patients and 55% (n = 11), respectively.These also occurred in 85.7% (n = 30) and 40% (n = 14) of patients in cohort B.

In addition, SAEs were reported in 21.4% (n = 12) of patients from the entire study, including 30% (n = 6) from cohort A and 17.1% (n = 6) in cohort B. Treatment-related SAEs occurred in 10.7% (n = 6) of patients in this study, including 15% (n = 3) of those in cohort A and 8.6% (n = 3) in cohort B.

“Overall, it’s well tolerated and well manageable. … We don’t have any additional safety signals here. And it is similar to what we have seen in other studies actually in terms of safety profiles. So nothing unexpected,” he explained.

Gründwald said the main point here is that the data supports the use of cabozantinib after IO failure as it is safe a feasible, and the only thing that will need further research is dose reduction.

“Our data really supports the use of cabozantinib after IO failure. I think that's the main message. It's safe, tolerable and it’s efficacious,” he concluded. “It supports the use of 40 (mg) as well as 60 (mg), and that I think is a novelty because 60 mg is the licensed dose for the use of cabozantinib vs. single agent.”

_Reference

_{Grünwald, V, Boegemann M, Rafiyan M-R, et al. Final analysis of a non-interventional study on cabozantinib in patients with advanced renal cell carcinoma after prior checkpoint inhibitor therapy (CaboCHECK). Presented at the 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; Abstract #357}