Cabozantinib versus other TKIs after CPI treatment in the Real-world Management of Patients with mRCC

8 Sep, 23

Introduction

CPIs are a treatment option for patients with mRCC, but there is limited clinical data on the efficacy of targeted therapies following CPI treatment. Cabozantinib is approved for use in patients with advanced RCC including after CPI treatment.

Aim

This retrospective observational cohort study evaluated outcomes with cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment.

Patient Profile

Eligible patients initiated TKI therapy and had received a CPI as their last systemic treatment prior to TKI therapy.

Methods

This retrospective observational cohort study
Treatment

Cabozantinib or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment.

Study Endpoints

The following real-world outcomes were assessed: 6-month response rate (RR_6months; primary); overall response rate (ORR); overall survival (OS); time to treatment discontinuation (TTD); rates of dose reductions, and discontinuation due to adverse events (AEs). The p value for RR_6months (χ2 test) was used to test for non-inferiority.

Results

Efficacy
Eligible patients (n = 247) had a mean (SD) age of 65.9 (10.5) years and 74.1% were male; 75.7% (n = 187) received cabozantinib and 24.3% (n = 60) received other TKIs.
All patients had intermediate or poor MSKCC score; more poor-risk patients received cabozantinib than other TKIs (28.9% vs 20%).
Outcomes data are shown in the Table 1.
Compared with other TKIs, cabozantinib was associated with a significantly higher RR_6months and ORR, and TTD was twice as long with cabozantinib.

Table 1

	Cabozantinib (n = 187)	Other TKI (n = 60)	*p value*
RR_6months, %	50.8	33.3	< 0.001
ORR, %	53.5	38.3	0.041
Overall survival rate, % (95% CI) 6 months 12 months 18 months	81.9 (75.5, 86.8) 61.5 (53.5, 68.4) 51.7 (43.1, 59.6)	75.1 (61.5, 84) 59.6 (44.7, 71.8) 45.9 (29.6, 60.7)	0.765
TTD, median months	6.2	3.1	0.015
Dose reductions, %	47.1	41.7	0.466
Discontinuation due to AEs, %	31.3	40.4	0.3143

Safety

Discontinuation due to AEs was more frequent with other TKIs than with cabozantinib, although this was not statistically significant; 21.7% of discontinuations occurred during the first 3 months of treatment.
AEs leading to discontinuation were consistent with the known safety profile of the products.

Conclusion

In this mRCC population, cabozantinib was used more frequently than other TKIs after CPI treatment.

Cabozantinib was an effective and well tolerated option post-CPI, with a high response rate in the real-world setting.

Cabozantinib was associated with a significantly higher response rate and a lower discontinuation rate due to AEs; TTD was double that of other TKIs.

Reference

J Clin Oncol.2021 39:15_suppl, e16539-e16539