ASCO 2017: Health-related quality of life as a marker of treatment benefit with nivolumab in platinum-refractory patients with metastatic or unresectable urothelial carcinoma from CheckMate 275

Chicago, IL ( Nivolumab is one of five FDA-approved immune checkpoint inhibitors for metastatic or advanced UC patients who have failed platinum-based chemotherapy. The CheckMate 275 trial demonstrated a 19.6% ORR with acceptable toxicity for patients treated with 3 mg/kg IV nivolumab every 2 weeks until treatment progression.1

In this abstract, the authors focus instead on the health-related quality of life (HRQOL) outcomes in the CheckMate 275 study, with a specific emphasis on whether HRQOL impact was a marker for treatment efficacy.

HRQOL was measured using three questionnaires: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), three-level EQ-5D (EQ-5D-3L) and the visual analog scale (VAS). Questionnaires were given at baseline and every 8 weeks thereafter for the first 48 weeks. Patients included in this analyss were those with scores recorded at baseline and at least one postbaseline assessment while on treatment.

Based on survey completion, 62% (168) of the original cohort were included. Statistically significant (P< 0.05) improvements in mean scores for the EORTC QLQ-C30 subscales measuring role, emotional, and social functioning; global health status/quality of life; nausea/vomiting; pain; dyspnea; insomnia; appetite loss; constipation; and diarrhea were observed at ≥1 time points. With the exception of cognitive functioning, no significant worsening in subscale scores was observed in the EORTC QLQ-C30. Statistically significant and clinically meaningful improvement (based on a minimally important difference of 7) in EQ-5D VAS was noted between weeks 17 and 41. EQ-5D-3L utility index scores based on the UK tariff remained stable during treatment.

They note that patients with objective response (complete or partial response) met criteria for significant improvement on all three scales. However, there is no clear analysis linking HRQoL outcomes with clinical outcomes.

Important limitations include:
1) Only patients staying on nivolumab had subsequent HRQoL assessments, as this was not assessed beyond two visits in patients who stopped treatment
2) As this is a single-arm study, the HRQoL changes cannot be attributed to the therapy or disease itself.

Based on this, the authors conclude that HRQOL either remained stable or improved across all measures while being treated with nivolumab. Unfortunately, while this study demonstrates that nivolumab is well tolerated from a HRQOL standpoint, it doesn’t add much value to the long-term discussion regarding selection.

Presented By: Andrea Necchi, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

1. Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.