A Q-TWiST Analysis Comparing Nivolumab and Therapy of Investigator's Choice in Patients with Recurrent/Metastatic Platinum-Refractory Squamous Cell Carcinoma of the Head and Neck

Abstract

Objectives: In the CheckMate 141 trial (NCT02105636), nivolumab demonstrated survival, health-related quality of life, and healthcare resource utilization benefits vs single-agent therapy of investigator's choice (IC) (methotrexate, docetaxel or cetuximab) in patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We assessed between-treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST).

Methods: Survival data from CheckMate 141 (nivolumab, n = 240; IC, n = 121) was partitioned into toxicity (TOX), time without symptoms or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3-4 adverse events after randomization, before disease progression. TWiST was defined as time not in TOX or REL. REL was defined as time between disease progression and death. Utility values derived from three-level EuroQol five-dimensional questionnaire data from CheckMate 141 were used to calculate Q-TWiST as the utility-weighted sum of the mean duration in each health state.

Results: The between-group difference in Q-TWiST score was 1.23 months (95% confidence interval 1.17-1.29) favoring nivolumab (p < 0.001). The nivolumab group experienced significantly longer mean time in TWiST (3.82 vs 2.78 months) and REL (4.02 vs 3.30 months) compared with the IC group (p < 0.001). Mean time in TOX was lower for nivolumab vs IC (0.30 vs 0.37 months, p < 0.001).

Conclusions: In CheckMate 141, nivolumab resulted in statistically significant and clinically meaningful gains (relative difference > 10%) in quality-adjusted survival vs standard of care in patients with R/M SCCHN.

Conflict of interest statement

Kim Cocks, Sarah Simpson, and Fiona Taylor are employees of Adelphi Values, which has received payment from Bristol-Myers Squibb for contracted analyses. Kim Cocks has also received personal fees from Amgen, AstraZeneca, Celgene, EndoMag, and Onyx Pharmaceuticals. James W. Shaw and Marta Contente are employees and shareholders of Bristol-Myers Squibb.

Figures

Fig. 1

Partitioned survival curve for a the nivolumab treatment arm, and b the investigator’s choice treatment arm. REL relapse, TOX toxicity, TWiST time without symptoms of disease progression or toxicity

Fig. 2

Threshold analysis using UK norms for utility of TWiST: a absolute difference in Q-TWiST, months with nivolumab compared with IC; b relative gain in Q-TWiST, months with nivolumab compared with IC. Utility values during TOX and REL vary from 0 to 1; the utility value for TWiST is held at 0.805 based on the UK population norm [16] weighted to the CheckMate 141 randomized population. Shading represents absolute and relative gain category for a given utility value of TOX and REL. Relative gain in Q-TWiST: difference between nivolumab and IC divided by median OS in IC arm (5.1 months). aAt a TOX utility value of 1 and a REL utility value of 0, relative gain was 14.9%. IC investigator’s choice, Q-TWiST quality-adjusted time without symptoms of disease progression or toxicity, REL relapse, TOX toxicity, TWiST time without symptoms of disease progression or toxicity