AT EsMO 2016

COPENHAGEN (FRONTLINE MEDICAL NEWS) – Among patients with recurrent or metastatic squamous cell carcinoma of the head and neck, those treated with the programmed death ligand–1 checkpoint inhibitor nivolumab reported consistently better quality of life than patients treated with a standard second-line agent of the investigator’s choice.

In a substudy of the randomized phase III Checkmate 141 trial, patients treated with nivolumab (Opdivo) had consistently stable outcomes across three separate, validated quality of life (QoL) instruments, reported Kevin Harrington, MBBS, of Royal Marsden Hospital in London.

“Nivolumab is the first PD-L1 [programmed death ligand–1] inhibitor to demonstrate a significant improvement in overall survival, with greater tolerability and a quality of life benefit, compared with standard of care therapy,” he said at the European Society of Medical Oncology Congress.

The overall trial results were reported at the 2016 annual meeting of the American Association for Cancer Research, and published online in the New England Journal of Medicine to coincide with Dr. Harrington’s presentation.

In this open-label trial, 361 patients with squamous cell carcinoma of the head and neck (HNSCC) that recurred or progressed within 6 months of completion of platinum-based chemotherapy were randomly assigned on a 2:1 basis to receive either nivolumab 3 mg/kg every 2 weeks, or standard, single-agent systemic chemotherapy with either methotrexate, docetaxel, or cetuximab.

After a median follow-up of 5.1 months (range, 0-16.8 months), the median overall survival, the primary endpoint, was 7.5 months for patients on nivolumab, compared with 5.1 months for those on standard therapy. The hazard ratio for death with nivolumab was 0.70 (P = .01). Estimates of 1-year survival were 36% vs. 16.6%, respectively. The median progression-free survival was similar between the groups, at 2 months and 2.3 months, respectively (a nonsignificant finding).

Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of patients on nivolumab, compared with 35.1% of those on standard therapy.

Patient-reported outcomes

Dr. Harrington reviewed changes from baseline in symptoms and function for three different patient-reported instruments:

• The cancer-specific EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30.

• The head and neck cancer–specific QLQ-H&N35.

• The generic health status EQ-5D-3L.

Patients were assessed on day 1 of the first treatment cycle, at week 9 and every 6 weeks thereafter of the study, at the first and second follow-up visits, and at survival follow-up visits (with the EQ-5D-3L only).

For the QLQ-C30 domains of physical, role, and social functioning, patients on nivolumab had either slight improvements from baseline or stayed the same, whereas patients on standard therapies had significant declines at both 9 and 15 weeks for all three domains.

There were no differences in functional domains on this instrument according to expression of PD-L1 (on either 1% or more of tumor cells or less than 1%).

For the EORTC QLQ-C30 symptom burden scale, patients assigned to the investigator’s choice had significantly and clinically meaningful worse symptoms, compared with patients on nivolumab at 9 and 15 weeks, and the median time to deterioration of function favored nivolumab on all subscales except for emotional functioning.

Similar differences in favor of nivolumab were seen in the EORTC QLQ-H&N35 instrument domains of pain, sensory problems, and social contact problems.

Lastly, on the EQ-5D-3L instrument, nivolumab-treated patients had stable health status, compared with worsening health status, with the difference statistically significant at week 15 (P = .037).

Anthony T.C. Chan, MD, professor of clinical oncology at the Chinese University of Hong Kong, the invited discussant, said that some of the differences in QoL noted in the study may have been due to differences between the therapies.

“The kinetics of adverse events with checkpoint blockade is now well described, and it’s quite different from systemic chemotherapy, where you get the side effects immediately. Quite often with checkpoint inhibitors, you can get adverse events up to 6-8 weeks or even longer after the start of therapy,” he said.

Nonetheless, “I think from [Checkmate 141] with the very positive results we’ve just seen with nivolumab, both in improving overall survival as well as improving patient-reported outcomes, after patients have failed platinum-based chemotherapy, nivolumab should be considered standard second-line therapy in this setting,” he said.

The trial was supported by Bristol-Myers Squibb. Dr. Harrington and Dr. Chan disclosed receiving research funding, serving as an adviser, and/or receiving travel, accommodations, and other expenses from the company.