Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial

Abstract

Background: The programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC).

Objective: To evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC.

Design, setting, and participants: We used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab.

Intervention: Intravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr.

Outcome measurements and statistical analysis: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression.

Results and limitations: In the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%.

Conclusions: These results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274.

Patient summary: Nivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

Keywords: Adjuvant; Bladder cancer; Immunotherapy; Invasive; Nivolumab; Phase 3; Quality of life; Radical cystectomy; Randomized controlled trial.

Fig. 1 –

Patient disposition for the EORTC QLQ-C30 evaluable and VAS evaluable populations. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; PD-L1 = programmed death ligand 1; VAS = visual analog scale.

Fig. 2 –

Linear mixed-effect model for repeated measures least squares mean change from baseline in HRQoL. (A) Physical functioning, (B) role functioning, and (C) fatigue for the EORTC QLQ-C30 evaluable population. (D) Physical functioning, (E) role functioning, and (F) fatigue for the EORTC QLQ-C30 evaluable population with PD-L1 expression ≥1%. CI = confidence interval; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; FU = follow-up; HRQoL = health-related quality of life; LS = least squares; W = week.

Fig. 3 –

Time to confirmed deterioration of HRQoL: (A) global health status/QoL, (B) physical functioning, (C) role functioning, (D) fatigue, and (E) VAS. The analysis used the overall EORTC QLQ-C30 evaluable and VAS evaluable populations. CI = confidence interval; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; HR = hazard ratio; HRQoL = health-related quality of life; QoL = quality of life; VAS = visual analog scale.

Fig. 3 –

Time to confirmed deterioration of HRQoL: (A) global health status/QoL, (B) physical functioning, (C) role functioning, (D) fatigue, and (E) VAS. The analysis used the overall EORTC QLQ-C30 evaluable and VAS evaluable populations. CI = confidence interval; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; HR = hazard ratio; HRQoL = health-related quality of life; QoL = quality of life; VAS = visual analog scale.