Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors

Abstract

BackgroundImmuno-oncology (IO) therapies have changed the treatment standards of metastatic renal cell carcinoma (mRCC). However, the effectiveness of targeted therapy following discontinuation of IO therapy in real-world settings has not been well studied. ObjectiveTo describe treatment sequence and assess clinical effectiveness of targeted therapy for mRCC patients who received prior IO therapy. Design, setting, and participantsA retrospective, longitudinal cohort study using data from eight international cancer centers was conducted. Patients with mRCC were ≥18yr old, received IO therapy in any line, and initiated targeted therapy following IO therapy discontinuation. InterventionPatients were treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) or mammalian target of rapamycin inhibitors (mTORIs). Outcome measurements and statistical analysisOutcomes were time to treatment discontinuation (TTD), overall survival (OS), and objective response rate (ORR). Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Models were adjusted for age, sex, therapy line, and International Metastatic RCC Database Consortium risk group. Results and limitationsAmong 314 patients, 276 (87.9%) and 38 (12.1%) were treated with VEGFR-TKI and mTORI therapy, respectively. The most common tyrosine kinase inhibitor treatments were axitinib, cabozantinib, and sunitinib following IO therapy. In adjusted models, patients treated with VEGFR-TKI versus mTORI therapy had lower hazard of TTD after IO treatment (aHR=0.46; 95% CI: 0.30–0.71; p < 0.01). One-year OS probability (65% vs 47%, p < 0.01) and proportion of ORR (29.8% vs 3.6%, p < 0.01) were significantly greater for patients treated with VEGFR-TKIs versus those treated with mTORIs. ConclusionsTargeted therapy has clinical activity following IO treatment. Patients who received VEGFR-TKIs versus mTORIs following IO therapy had improved clinical outcomes. These findings may help inform treatment guidelines and clinical practice for patients post-IO therapy. Patient summaryPatients may continue to experience clinical benefits from targeted therapies after progression on immuno-oncology treatment.