1 Pembrolizumab Plus Belzutifan Versus Pembrolizumab Plus Placebo as Adjuvant Therapy for Renal Cell Carcinoma: Patient-Reported Outcomes in LITESPARK-022

Vollständiger Abstract

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Abstract Background The randomized, double-blind, phase 3 LITESPARK-022 study (NCT05239728) showed significant disease-free survival benefit with the addition of belzutifan to adjuvant pembrolizumab in participants with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence following surgery. We present patient-reported outcome (PRO) findings for LITESPARK-022. Methods Adults with ccRCC stage M0 and intermediate-high or high risk of recurrence after nephrectomy or stage M1 with no evidence of disease after surgery were randomly assigned 1:1 to receive pembrolizumab with either belzutifan or placebo. PROs were evaluated in all randomly assigned participants with ≥1 dose study treatment and ≥1 completed assessment. The Functional Assessment of Cancer Therapy–Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS), European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), and Functional Assessment of Cancer Therapy–General item 5 (FACT-GP5) were done on day 1 at cycles 1-3, 5, 7, and 9 and during the efficacy follow-up after treatment discontinuation or completion. Assessments continued for 3 years from randomization until recurrence or new therapy. Prespecified secondary end points included least square mean change from baseline to week 84 in symptom scores measured by FKSI-DRS and health-related quality of life (HRQoL) by QLQ-C30 global health status/quality of life (GHS/QoL), physical functioning (PF), and role functioning (RF) scores. The analysis time point was week 84 (last time point where completion and compliance rates of ≥ 60% and ≥80%, respectively, were observed). PRO analyses were descriptive and not formally statistically tested. Results Median follow-up was 28.4 months (range, 15.0-40.1). Of 1841 randomized participants, 907 in the pembrolizumab plus belzutifan group and 912 in the pembrolizumab plus placebo group completed ≥1 PRO assessment and were included in the PRO analysis set. Completion and compliance rates for FKSI-DRS and EORTC QLQ-C30 were >90% at baseline for both instruments and were >60% and >80%, respectively, at week 84. Least square mean change from baseline to week 84 was −0.67 with pembrolizumab plus belzutifan versus −0.76 with pembrolizumab plus placebo (difference 0.10 [95% CI, −0.28 to 0.47]) in FKSI-DRS score; −2.18 with pembrolizumab plus belzutifan versus −1.95 with pembrolizumab plus placebo (difference −0.23 [95% CI, −1.95 to 1.49]) in QLQ-C30 GHS/QoL score; −1.67 with pembrolizumab plus belzutifan versus −2.38 with pembrolizumab plus placebo (difference 0.71 [95% CI, −0.66 to 2.09]) in QLQ-C30 PF score; and −1.14 with pembrolizumab plus belzutifan versus −1.86 with pembrolizumab plus placebo (difference 0.72 [95% CI, −1.27 to 2.71]) in QLQ-C30 RF score. According to FACT-GP5, most participants in both groups (≥80%) reported being affected either “not at all” or “a little bit” by side effects of treatment across all time points. Conclusions No clinically meaningful changes in PROs from baseline to week 84 were observed with either adjuvant pembrolizumab plus belzutifan or adjuvant pembrolizumab plus placebo, and PRO findings were similar between the 2 groups. The totality of efficacy, safety, and PRO results support the potential use of adjuvant pembrolizumab plus belzutifan in patients with RCC at increased risk of recurrence after surgery.