Author: Jason Harris
Patients with head and neck squamous cell carcinoma (HNSCC) saw improved or stable quality of life (QOL) scores following treatment with single-agent nivolumab (Opdivo), according to results published in Lancet Oncology.1
In contrast, patients assigned to investigator’s choice of treatment saw clinical meaningful declines, defined as a decrease in ≥10% from baseline, across 8 of 15 (53%) domains on the EORTC QLQ-C30 questionnaire.
“The results of CheckMate-141 suggest that nivolumab is the first PD-1 inhibitor, to our knowledge, to show a significant improvement in overall survival, with better tolerability and a quality-of-life benefit, compared with standard therapy for platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck,” investigators wrote. “In view of the major unmet need in this population and the importance of maintaining or improving quality of life for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, these data support nivolumab as a new standard of care option in this setting.”
Investigators evaluated statistical differences in patient-reported adjusted mean changes from baseline between treatment groups as assessed by the EORTC QLQ-C30, EORTC QLQ-H&N35, and EQ-5D-3L at each time point, and the time to clinically meaningful deterioration per each individual scale’s criteria.
Patient assessments were conducted before treatment initiation, at week 9, and then every 6 weeks during the treatment period using the EORTC QLQ-C30, EORTC QLQ-H&N35, and EQ-5D-3L questionnaires. Posttreatment assessments were made at follow-up visits 1 and 2 (35 days give or take 7 days after the last treatment dose, and 80 days give or take 7 days after follow-up visit 1). The EQ-5D-3L questionnaire was also administered at survival follow-up visits (every 3 months give or take 7 days after follow-up visit 2). Patients completed their assessments at each time point before physician contact, treatment dosing, or any procedures.
Thirty-six patients assigned to investigator’s choice of treatment with platinum-based chemotherapy and 93 patients assigned to nivolumab completed 15 weeks of QoL assessment.
Adjusted mean differences between the treatment groups were significant and clinically meaningful, defined as a difference of 10 points or greater, in favor of nivolumab for role functioning, social functioning, fatigue, dyspnea, and appetite loss at both weeks 9 and 15. Investigators also observed significant and clinically meaningful differences favoring nivolumab for diarrhea week 9, and at week 15 for physical functioning, cognitive functioning, and insomnia.
Nivolumab significantly delayed median time to deterioration compared with investigator’s choice for pain, sensory problems, social contact problems, and mouth opening problems on the EORTC QLQ-H&N35 questionnaire. Patients in the nivolumab group reached median time to clinically meaningful increase in weight, but not in the investigator’s choice group.
The EQ-5D VAS, a measure of the patient’s overall health status, was similar between groups at baseline for the analytical cohort (n = 124) and all-randomized population. However, patients in the nivolumab group had a clinically meaningful improvement, defined as a difference of ≥7 points, in adjusted mean change in VAS score from baseline to week 15 compared with clinically meaningful deterioration in the investigator’s choice group (7.3 vs -7.8). The difference between groups at week 15 favoring nivolumab was both significant and clinically meaningful. Median time to deterioration on the EQ-5D VAS was not significantly different between the treatment groups.
CheckMate-141 was an international, phase III, randomized, open-label study investigating comparing overall survival (OS) with nivolumab versus single-agent therapy of investigator’s choice in patients with platinum-refractory recurrent or metastatic HNSCC. Patients were treated at 66 sites in 15 countries in North America, Asia, Europe, and South America.
Patients with cancer of the oral cavity, pharynx, or larynx were randomly assigned to 3 mg/kg nivolumab every 2 weeks (n = 240) or investigator’s choice of cetuximab (12.4%), methotrexate (44.6%), or docetaxel (43%; N = 121). Cetuximab was administered at 400 mg/m2 for the first dose followed by 250 mg/m2 weekly. Methotrexate was administered at 40 mg/m2weekly. Docetaxel was administered at 30 mg/m2 weekly.
Median age was 60 years, and 31.3% were ≥65 years of age. Most patients were male (83%), Caucasian (83%), and had an ECOG PS of 1 (78.4%). Most patients received ≥2 prior systemic therapies (54.8%), and over 90% had received prior radiation therapy. HPV status was known for 49.3% of patients, using p16 status, and PD-L1 expression was available for 72% of enrolled patients.
In survival data first presented at the 2016 ASCO Annual Meeting, the median OS was 7.5 months with nivolumab compared with 5.1 months with investigator’s choice (HR, 0.70; 95% CI, 0.51-0.96; P = .0101). The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice.2
The 1-year OS rates were 36% with nivolumab (95% CI, 28.5-43.4) compared with 16.6% for investigator’s choice (95% CI, 8.6-26.8). Similar improvements in survival were seen across demographic subgroups. The median progression-free survival (PFS) was 2.0 months with nivolumab versus 2.3 months with investigator’s choice (HR, 0.89; 95% CI, 0.70-1.10; P = .3236). The 6-year PFS rates were 19.7% for nivolumab and 9.9% for investigator’s choice of therapy.
Writing in an accompanying editorial, Susanne Singer, PhD, chair of the division of Epidemiology and Health Services Research at the Institute of Medical Biostatistics, Epidemiology and Informatics of University Medical Centre of Johannes Gutenberg-University Mainz, listed three caveats about the QoL findings: 1) new drugs have different toxicity profiles than standard chemotherapy and that may affect QoL domains that are not covered by standard instruments; 2) there were no hypotheses and many tests were done without adjustment for multiplicity because the QoL analysis was exploratory, so these results should not be given the same weight as a confirmatory analysis; and 3) Baseline QoL may not be an appropriate metric because patients with advanced disease and poor QoL usually drop out from trials more frequently than do patients with better QoL.3
“Bearing these limitations in mind, Checkmate-141 offers valuable insight into the potential effects of nivolumab on certain QoL domains in patients with advanced head and neck cancer who are reasonably fit (ECOG performance status of 0 or 1),” she wrote. “Domains that are most important to patients with head and neck cancer according to an international EORTC study are worrying, swallowing, talking, eating, sticky saliva, dry mouth, and pain in the mouth. In all of these areas, patients treated with nivolumab reported better QoL both 9 and 15 weeks after than patients treated with investigator’s choice.”
1.Harrington KJ, Ferris RL, Blumenschein G, 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 [published online June 23, 2017]. Lancet Oncol. doi: 10.1016/S1470-2045(17)30421-7.
2.Ferris RL, Blumenschein GR, Fayette J, et al. Further evaluations of nivolumab (nivo) versus investigator’s choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141. J Clin Oncol. 2016;34 (suppl; abstr 6009).
3.Singer S. Quality of life after nivolumab treatment for head and neck cancer [published online June 23, 2017]. Lancet Oncol. doi: 10.1016/S1470-2045(17)30463-1.