Immunotherapy Agent Improves Quality of Life in Head and Neck Cancer

Quality of life (QOL) was either improved or stabilized for patients with head and neck squamous cell carcinoma (HNSCC) who were treated with Opdivo (nivolumab) as a single agent, according to recent results from a study published in Lancet Oncology.

In contrast, patients assigned to investigator’s choice of treatment saw clinical meaningful declines, defined as a decrease in 10 percent or more from baseline, across eight of 15 (53 percent)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 nine, and then every six 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 one and two (35 days give or take seven days after the last treatment dose, and 80 days give or take seven days after follow-up visit 1). The EQ-5D-3L questionnaire was also administered at survival follow-up visits (every three months give or take seven days after follow-up visit two). 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 Opdivo 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 Opdivo for role functioning, social functioning, fatigue, dyspnea, and appetite loss at both weeks nine and 15. Investigators also observed significant and clinically meaningful differences favoring Opdivo for diarrhea week nine, and at week 15 for physical functioning, cognitive functioning and insomnia.

Opdivo 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 Opdivo 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 (124 patients) and all-randomized population. However, patients in the Opdivo group had a clinically meaningful improvement, defined as a difference of seven or more 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 Opdivo 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 3, randomized, open-label study investigating comparing overall survival (OS) with Opdivo 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 Opdivo every two weeks (240 patients) or investigator's choice of cetuximab (12.4 percent), methotrexate (44.6 percent) or docetaxel (43 percent; 121 patients). 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 percent were at least 65 years of age. Most patients were male (83 percent), Caucasian (83 percent), and had an ECOG PS of 1 (78.4 percent). Most patients received at least two prior systemic therapies (54.8 percent), and over 90 percent had received prior radiation therapy. HPV status was known for 49.3 percent of patients, using p16 status, and PD-L1 expression was available for 72 percent of enrolled patients.

In survival data first presented at the 2016 ASCO Annual Meeting, the median OS was 7.5 months with Opdivo compared with 5.1 months with investigator's choice. The objective response rate (ORR) was 13.3 percent with Opdivo and 5.8 percent for investigator's choice.

The one-year OS rates were 36 percent with Opdivo compared with 16.6 percent for investigator’s choice. Similar improvements in survival were seen across demographic subgroups. The median progression-free survival (PFS) was two months with Opdivo versus 2.3 months with investigator's choice. The six-year PFS rates were 19.7 percent for Opdivo and 9.9 percent for investigator's choice of therapy.

Writing in an accompanying editorial, Susanne Singer, Ph.D., 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.

“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 nine and 15 weeks after than patients treated with investigator’s choice.”