ESMO 2016 Press Release: Nivolumab Maintains Function and Reduces Symptoms in Relapsed Metastatic Head and Neck Cancer

LUGANO-COPENHAGEN – Nivolumab maintains function and reduces symptoms in treatment of relapsed metastatic head and neck cancer, according to results from the CheckMate 141 trial presented at the ESMO 2016 Congress in Copenhagen and published in the New England Journal of Medicine.

CheckMate 141 is a randomised, open label phase III trial in which 361 patients with platinum refractory relapsed head and neck cancer received treatment with nivolumab or standard of care chemotherapy (physician’s choice of  methotrexate, docetaxel or cetuximab). As previously reported, nivolumab improved overall survival by an average of 2.5 months.

For the first time today the investigators presented the results of patient reported outcomes, including functional capacity and symptoms. The analysis included 129 patients who completed questionnaires at baseline, nine weeks and at six week intervals during treatment. Questions covered functional areas, such as their physical ability to perform their role in life (job, etc) and their emotional, cognitive and social wellbeing. They were also asked about symptoms such as fatigue, nausea, pain and shortness of breath. An overall score was calculated for global health.

Within each treatment arm the questionnaire results were tracked from baseline to nine weeks and 15 weeks. The investigators also compared the results between the two treatment arms at nine weeks and 15 weeks using previously defined score differences defining a clinically relevant gap (for some domains it was a gap of seven points while for others it was a gap of ten points).

For patients receiving nivolumab, both function and symptom burden was maintained or even improved at nine and 15 weeks compared to baseline. In contrast, patients receiving standard of care chemotherapy had worse scores in all areas at nine and 15 weeks compared to baseline.

When the investigators compared the scores between the two treatment arms at nine and 15 weeks, they found that for most of the function and symptom areas, nivolumab gave a clinical significant benefit over standard of care chemotherapy.

“Nivolumab not only prolongs life but it does so while maintaining function and reducing symptoms compared with standard of care chemotherapy,” said lead author Professor Kevin Harrington, joint head of the Division of Radiotherapy and Imaging, at the Institute of Cancer Research, London, UK and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust.

“We need to drill down into the data to understand the reasons for these findings,” he continued. “The data suggest that the superior clinical activity of nivolumab maintains patient-reported outcomes, but it is also likely that nivolumab is a kinder treatment that is associated with fewer side effects which can have a negative effect on quality of life.”

“We’re used to the notion that for gain there has to be pain, and that we have to ask patients to accept more toxicity to get better outcomes,” said Harrington. “But immunotherapy with nivolumab gives better survival and allows patients to function at work and socially, and experience less pain and fatigue than with chemotherapy. This is a win-win scenario for patients and their doctors.”

Commenting on the study, Professor Sandrine Faivre, a medical oncologist at Beaujon University Hospital, Clichy, France said: “This study assessed symptoms and quality of life using several questionnaires, including one specifically designed for patients with head and neck cancer. This is important because these tumours have particular consequences. A tumour mass in the neck, for example, is painful and may impair eating and speaking functions. It is also visible and can lead to social isolation.”

“This is the first study to show that an immunotherapy is superior to classical treatment options for improving quality of life and symptoms, on top of prolonging survival,” continued Faivre. “I can now explain to my patients that nivolumab may help them to feel and function better in daily life.”

She concluded: “Nivolumab works in around one-third of patients with advanced head and neck cancer. We need biomarkers or biological criteria to identify patients most likely to benefit from this treatment so that unnecessary side effects and costs are avoided.”

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Notes to Editors

References and notes

Abstract LBA4 - ‘Patient-Reported Outcomes (PROs) in Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treated with Nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141,‘ will be presented by Professor Kevin Harrington during Presidential Symposium 2 on Sunday, 9 October, 16:30 – 18:20 (CEST).

Gillison M, Ferris R, Blumenschein G, et al. Nivolumab for recurrent squamous cell carcinoma of the head and neck. N Engl J Med. DOI: 10.1056/NEJMoa1602252

The questionnaires were the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQ-H&N35) and the EuroQol five dimensions’ questionnaire (EQ-5D).

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Abstract LBA4_PR

Patient-Reported Outcomes (PROs) in Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treated with Nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141

K. Harrington1, R.L. Ferris2, J. Shaw3, F. Taylor4, M. Derosa4, D. Turner-Bowker4, L. Morrissey4, K. Cocks5, N. Kiyota6, M. Gillison7, J. Guigay8

1Division of Radiotherapy and Imaging, Institute of Cancer Research ICR, London, UK, 2Division of Head and Neck Surgery Departments of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 3Clinical Outcomes Assessment and I-O LCM Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA, 4Patient-Centered Outcomes, Adelphi Values, Boston, MA, USA, 5Patient-Centered Outcomes, Adelphi Values, Cheshire, UK, 6Medicine of Oncology, Kobe University Hospital, Kobe, Japan, 7Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA, 8Medical Oncology Department, Centre Antoine Lacassagne, Nice, France

Background: Patients (pts) with platinum-refractory R/M SCCHN have median survival ≤6 mo and suffer from their disease and its treatment. Accordingly, maintaining quality of life (QoL) is a key treatment goal. PRO data were collected as exploratory endpoints in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial comparing nivo to IC (methotrexate, docetaxel, or cetuximab) in 361 pts with platinum-refractory R/M SCCHN. We report the first comparative results for PRO for nivo and IC in R/M SCCHN.

Methods: The European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQ-H&N35), and EQ-5D were administered at baseline (BL), wk 9, and then at 6-wk intervals during treatment. A clinically relevant score change or difference was regarded as 10 points for the EORTC subscales. Analysis of covariance (ANCOVA) was applied to compare mean score changes between arms. Proportional hazards regression was used to evaluate time to clinically relevant score deterioration (TTD).

Results: BL questionnaire completion rates for nivo and IC were ~80% and ~75%, respectively. Low IC completion rates precluded analysis of mean differences after wk 15. Overall, 129 pts completed a PRO measure at BL and during follow up. Nivo significantly delayed TTD (P<0.05, 2-tailed) vs IC for global health; physical, role, cognitive, and social functioning; fatigue; dyspnea; and insomnia (EORTC QLQ-C30) as well as pain; sensory problems; and mouth opening problems (QLQ-H&N35). ANCOVA revealed statistically significant, clinically relevant differences favoring nivo at wks 9 and 15 for role and social functioning, fatigue, dyspnea, and appetite loss (EORTC QLQ-C30) as well as pain and sensory problems (QLQ-H&N35). Differences in mean values were observed for other PROs at wk 15 only.

Conclusions: Pts treated with nivo had delayed worsening of functioning and symptoms with PRO differences between arms favoring nivo up to ~4 mo of follow up. These results, as assessed through wk 15, suggest that pts receiving nivo maintained functioning for longer and had less pain, fatigue, and dyspnea on treatment as compared with IC.

Clinical trial identification: NCT02105636; Study start date, May 2014 

Legal entity responsible for the study: Sponsored by Bristol-Myers Squibb

Funding: Bristol-Myers Squibb

Disclosure:

K. Harrington: Personal fees and fees paid to research institution from BMS, during the study; Fees paid to research institution by AstraZeneca and Pfizer; Personal fees and fees paid to research institution from Merck and Amgen, outside submitted work. 
R.L. Ferris: Grants and consulting/advisory board member for AstraZeneca, Merck, and BMS; Consulting/advisory board member for Pfizer.
J. Shaw: Employee and shareholder of Bristol-Myers Squibb.
F. Taylor: Employee of Adelphi Values, a consulting firm paid by BMS to analyze clinical trial PRO data
D. Turner-Bowker: Employee of Adelphi Values, which received funding to conduct this research.
L. Morrissey: Employee of Adelphi Values, which was paid for the statistical analyses.
K. Cocks: Employee of Adelphi Values, which is a paid consultant of BMS.
N. Kiyota: Grants & personal fees from ONO Pharmaceutical Co, Ltd, during the study; Grants from Eisai Co, Ltd, and Nippon Boehringer Ingelheim Co, Ltd, outside submitted work; Payment for seminar participation from BMS, Merck Serono, and Bayer.
M. Gillison: Consulting for BMS, Lilly, and Merck Inc.
J. Guigay: Grants from and advisory board member for Merck; Grants from GSK; Advisory board member for BMS and Innate Pharma
All other authors have declared no conflicts of interest.

Keywords: patient reported outcomes, quality of life, head and neck cancer