Abstract 683P
Background
RASi have been shown to improve outcomes in studies of multiple malignancies by effects on the tumor microenvironment to enhance the immune repertoire and improve drug delivery. We evaluated the impact of RASi on outcomes in mRCC patients receiving ICI.
Methods
This multicenter, retrospective cohort study included mRCC patients treated with ICI with or without RASi. The patients from Dana-Farber Cancer Institute (DFCI) were used as a discovery cohort, and the patients from University of California San Diego (UCSD) were used for validation. Receipt of an ICI (PD1/L1 and/or CTLA-4 inhibitors) was required. RASi use was defined as receipt of a RASi at baseline and for a minimum of 30 days after ICI initiation. For both cohorts, the primary outcome assessed was overall survival (OS) and the secondary endpoints were time-to-treatment failure (TTF), and objective response rate (ORR). Propensity score matching was performed in both cohorts.
Results
Overall, 229 patients who received an ICI were included: 100 patients from DFCI and 129 patients from UCSD. Concomitant RASi were administered in 30 patients (30%) in the DFCI cohort and 59 (45%) in the UCSD cohort. Median age at ICI initiation was 62.5 years in both cohorts. Median follow-up was 3.8[IQR=3–5.3] years in the DFCI cohort, and 2.3[IQR=1.4–3.6] years in the UCSD cohort. In the DFCI cohort, RASi was significantly associated with longer OS (adjusted-HR=0.35 [95% CI: 0.17–0.70], P=0.003) and TTF (adjusted-HR = 0.57 [0.36–0.92], P=0.02). In the validation cohort, RASi was associated with TTF (adjusted HR=0.60 [0.39–0.92], P=0.02) and trended for association with OS (adjusted-HR=0.60 [0.34–1.06], P=0.07). The propensity analysis, matching 83 patients from both cohorts receiving RASi while on ICI with 83 who did not, showed that RASi significantly improved OS (HR=0.59 [0.37–0.95], P=0.03) and TTF (HR=0.60 [0.43–0.85], P=0.0034).
Conclusions
Repurposing RASi to treat metastatic renal cell carcinoma (mRCC) in combination with immune-checkpoint inhibitors (ICI) improved OS and TTF coupled with tolerability and cost efficacy. This provides a rationale for prospective randomized studies combining ICI and RASi in mRCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.