Nivolumab is the first agent to demonstrate a significant survival benefit in this population [resistant head and neck squamous cell carcinoma] in a randomized phase III trial. This is an incredible finding.
—Maura Gillison, MD, PhD
Squamous cell carcinoma of the head and neck that progresses after platinum-based therapy has a dismal prognosis, and there is no effective standard of care. No treatment has improved survival for this patient population, but that may be about to change.
Nivolumab (Opdivo), an anti–PD-1 (programmed cell death protein 1) checkpoint inhibitor, improved survival in patients with squamous cell carcinoma of the head and neck who progressed within 6 months of platinum therapy as part of the initial treatment for recurrent or metastatic disease, according to the interim results of the phase III CheckMate-141 trial reported at the 2016 Annual Meeting of the American Association for Cancer Research (AACR).1
Patients with squamous cell carcinoma of the head and neck that progresses after platinum-based therapy have an average survival of less than 6 months. In CheckMate-141, nivolumab reduced the risk of death by 30% compared with standard therapy using investigator’s choice (P = .0101). One-year survival was 36% in the nivolumab arm vs 16.6% in the control arm, representing an absolute improvement of 20%. Median overall survival was 7.5 months for nivolumab vs 5.1 months for those assigned to investigator’s choice.
Lead investigator Maura Gillison, MD, PhD, of The Ohio State University Comprehensive Cancer Center, Columbus, was thrilled to present these results. “We have never seen this before in this patient population. Nivolumab is the first agent to demonstrate a significant survival benefit in this population in a randomized phase III trial. This is an incredible finding. Most important is that the proportion of patients in the nivolumab arm who survived 1 year was double that of the control arm.”
“The survival benefit was observed in the overall study population, regardless of tumor PD-L1 [programmed cell death ligand 1] expression or human papillomavirus (HPV) p16 status. The safety profile of nivolumab was favorable compared to investigator’s choice therapy and consistent with prior studies. Nivolumab represents a new standard of care option for patients with squamous cell carcinoma of the head and neck who progress after platinum-based therapy,” Dr. Gillison stated.
CheckMate-141 enrolled 361 patients with relapsed or metastatic squamous cell carcinoma of the head and neck of the oral cavity, pharynx, or larynx that progressed within 6 months of platinum-based therapy. They were randomized 2:1 to receive nivolumab at 3 mg/kg every 2 weeks or weekly treatment with investigator’s choice (methotrexate, docetaxel, or cetuximab [Erbitux]). HPV status was documented by p16 expression.
“The investigator’s choice arm represents standard of care for these patients. This is based on response data, not survival data,” Dr. Gillison said.
Whether or not patients would respond to nivolumab was evident within 3 months. For the first 3 months, the survival curves overlapped, and after that they diverged. Results were so striking in favor of nivolumab at the interim analysis that the study was stopped.
Survival Benefit in All Subgroups
Nivolumab provided a survival benefit in every subgroup, regardless of PD-L1 status or HPV p16 status, but the magnitude of benefit was greater in those who stained positive for PD-L1 ≥ 1% and in HPV-positive cancers. “In those subgroups, nivolumab reduced the risk of death by approximately 50%,” she said.
Among patients with HPV-positive disease, median overall survival was 9.1 months for nivolumab vs 4.4 months for investigator’s choice. Among HPV-negative patients, median overall survival was 7.5 months vs 5.8 months, respectively.
The cutoff for PD-L1 positivity was ≥ 1%; 54.7% had PD-L1 ≥ 1% in the nivolumab arm, and 61.6% were PD-L1–positive in the investigator’s choice arm. Among PD-L1–positive patients, median overall survival was 8.7 months for nivolumab vs 4.6 months for investigator’s choice. Among patients with PD-L1 < 1%, median overall survival was 5.7 months for nivolumab vs 5.8 months with investigator’s choice.
“However, some people with PD-L1 < 1% are alive at 12 months in the nivolumab arm, so PD-L1 is not a reliable predictive marker,” she added.
The safety profile of nivolumab was consistent with what has already been published in other cancers. Only 58.9% of patients experienced any treatment-related toxicity in the nivolumab arm vs 77% in those treated with investigator’s choice of therapy. The rate of grade 3 or 4 adverse events was 13% with nivolumab vs 35% for investigator’s choice.
Progression-free survival, subgroup analysis by prior cetuximab therapy, quality-of-life analysis, and biomarker analysis will be reported in the future. Trials are now ongoing with checkpoint inhibitors in combination therapy and as first-line therapy in head and neck cancer. “The field is moving rapidly. It is very exciting,” Dr. Gillison said.
Raymond N. DuBois, MD
“This study will receive a lot of attention among practicing oncologists and will undoubtedly change the standard of care,” said Raymond N. DuBois, MD, AACR Past President and Dean of the Medical University of South Carolina College of Medicine, Charleston, who moderated a press conference where Dr. Gillison released these findings. ■
Disclosure: Dr. Gillison is a consultant for BMS, Lilly, and Merck.
1. Gillison ML, Blumenschein G Jr, Fayette J, et al: Nivolumab vs investigator’s choice for recurrent or metastatic head and neck squamous cell carcinoma: CheckMate-141. 2016 AACR Annual Meeting. Abstract CT099. Presented April 19, 2016.
“This is an important study,” said formal discussant Lillian L. Siu, MD, FASCO, Professor, University of Toronto Cancer Care Ontario Research Chair and medical oncologist at Princess Margaret Cancer Centre Drug Development Program in Toronto, Ontario, Canada. “No new drugs have been approved by the ...