Nivolumab Improved Patient-Reported QOL Compared With Investigator's Choice: CheckMate 141

June 28, 2017

The study, published in Lancet Oncology, has found that nivolumab reduced the rate of clinically meaningful deterioration compared with investigator’s choice among platinum-refractory patients being treated for recurrent or metastatic head and neck cancer.

A new study published in Lancet Oncology has found that nivolumab reduced the rate of clinically meaningful deterioration compared with investigator’s choice of single-agent cetuximab, methotrexate, or docetaxel among platinum-refractory patients being treated for recurrent or metastatic head and neck cancer who participated in the CheckMate 141 trial.

Patients were randomly assigned to receive nivolumab 3 mg/kg every 2 weeks (n = 240) or investigator's choice (n = 121) of methotrexate (40 mg/m2 to 60 mg/m2 of body surface area), docetaxel (30 mg/m2 to 40 mg/m2), or cetuximab (250 mg/m2 after a loading dose of 400 mg/m2) until disease progression, intolerable toxicity, or withdrawal of consent. However, the phase 3 trial was stopped early in January 2016 after an independent Data Monitoring Committee found that nivolumab improved overall survival in patients with squamous cell carcinoma of the head and neck, compared with the control arm.

Following a protocol amendment that allowed patient’s in the investigator’s choice group to cross over to nivolumab, and long-term survival is being monitored in patients not on active treatment. The trial also added an exploratory endpoint of patient-reported outcomes (PROs), to be assessed at baseline, week 9, and every 6 weeks thereafter using:

  • The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire—Core 30 (QLQ-C30)
  • The EORTC head and neck cancer-specific module (EORTC QLQ-H&N35)
  • The 3-level European Quality of Life—5 Dimensions (EQ-5D) questionnaire

All patients were included in the analyses for time to meaningful deterioration.

Of the 129 patients who completed the PRO questionnaires at baseline and at least 1 other assessment, 93 were in the nivolumab group and 36 in the investigator’s choice group. Functional and symptom domains, measured by the EORTC QLQ-C30, saw adjusted mean changes from baseline to week 15 following nivolumab treatment that ranged from -2.1 to 5.4, with no clinically meaningful deterioration in any domain. However, patients in the investigator’s choice group saw a clinically meaningful deterioration (of 10 points or more) in 8 of the 15 domains (53%) at week 15 (range for change from baseline, —24.5 to 2.4).

EORTC QLQ-H&N35 scale did not measure any clinically meaningful worsening at week 15 for any domains in the nivolumab-treated group, but did for 8 of 18 domains (44%) in the investigator’s choice group. The EQ-5D visual analogue scale measured a clinically meaningful improvement (a difference of 7 points or greater) in the nivolumab group (7.3), while the investigator’s choice group recorded a clinically meaningful deterioration (—7.8).

Overall, the study found that the median time to deterioration was significantly longer for the investigator’s choice treatments, compared with nivolumab, for 13 of 35 (37%) domains assessed across the 3 questionnaires.

The authors conclude that nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of investigator’s choice in the above patient population, thereby supporting the use of nivolumab as standard of care in this setting.

Reference

Harrington KJ, Ferris RL, Blumenschein G Jr, et al. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017;pii:S1470-2045(17):30421-30427. doi: 10.1016/S1470-2045(17)30421-7.