ESMO 2017: KEYNOTE-040 Evaluates Pembrolizumab in Head and Neck Cancer

Key Points

  • Median overall survival was only marginally higher in the pembrolizumab arm compared to standard treatment arm (8.4 vs 7.1 months).
  • Among patients with PD-L1 expression in more than 1% of all cells in their tumor, median overall survival was 8.7 months with pembrolizumab vs 7.1 months with standard treatments. Among patients with PD-L1 expression in more than 50% of their cancer cells, median overall survival was 11.6 vs 7.9 months, respectively.
  • In almost every category, pembrolizumab had a better side effect profile vs standard treatments. The exception is hypothyroidism, which occurred in 13% of those treated with pembrolizumab vs only 1% of those given other treatments.

Immunotherapy with the checkpoint inhibitor pembrolizumab (Keytruda) may be a better option than standard treatments for patients whose head and neck cancer has spread or recurred after an initial round of chemotherapy, according to results of the KEYNOTE-040 trial presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid (Abstract LBA45_PR).

Although the 19% improvement in overall survival among patients treated with pembrolizumab did not meet the prespecified difference for statistical significance, it was nevertheless a clinically meaningful difference for this population who only lived 7 to 8 months on average after initiating treatment, said lead investigator Ezra Cohen, MD, from the University of California, San Diego Moores Cancer Center, in La Jolla, California. 

“Even though the study did not meet its primary endpoint, I still think it is a positive trial,” Dr. Cohen said. “It reinforces that pembrolizumab should continue to be offered as an important option for all patients with this devastating disease.” 

More About KEYNOTE-040

The KEYNOTE-040 trial was a global, open-label, phase III study, which included patients with recurrent or metastatic head and neck squamous cell carcinoma after a platinum-based chemotherapy.

Patients were randomized to receive either pembrolizumab (n = 247) or standard-of-care treatment (n = 248), which was the investigator’s choice of either methotrexate, docetaxel, or cetuximab (Erbitux).

Median overall survival was only marginally higher in the pembrolizumab compared to standard treatment arm (8.4 vs 7.1 months, hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.66–0.99, P = .0204). However, for a subset of patients who had programmed cell death ligand 1 (PD-L1)–expressing tumors, pembrolizumab was associated with dramatic and significantly improved outcomes.

Specifically, among patients with PD-L1 expression in more than 1% of all cells in their tumor, median overall survival was 8.7 months with pembrolizumab vs 7.1 months with standard treatments (HR = 0.75; 95% CI = 0.59–0.95, P =.0078). Among patients with PD-L1 expression in more than 50% of their cancer cells, median overall survival was 11.6 vs 7.9 months, respectively (HR = 0.54; 95% CI = 0.35–0.82, P = .0017).

Compared to the other treatments, pembrolizumab measured up well in terms of side effects.

“In almost every category, it had a better side effect profile…vs standard treatments,” said Dr. Cohen. “The exception is hypothyroidism, which occurred in 13% of those treated with pembro[lizumab] vs only 1% of those given other treatments.”

Overall, Dr. Cohen said the KEYNOTE-040 trial reinforces what is already known about anti–PD-L1 therapy in head and neck cancer. “From a clinician’s perspective, I would feel the same in any country. This is a meaningful therapy that improves survival.”

Commentary

Asked to comment for ESMO, Amanda Psyrri, MD, PhD, from the University of Athens Medical School and Attikon University Hospital in Athens, Greece, said, “KEYNOTE-040 did not reach its primary endpoint of overall survival; however, pembrolizumab was superior to investigator’s choice in terms of toxicity, an important consideration in treatment decisions for these poor-prognosis patients with recurrent/metastatic platinum-refractory head and neck squamous cell carcinoma. As the authors point out, subsequent immunotherapy in the standard-of-care arm may have confounded overall survival analysis. The magnitude of treatment effect was greater in patients with PD-L1 combined positive score ≥ 1%, especially those with combined positive score ≥ 50%, suggesting that pembrolizumab may represent the preferable treatment option for this subset of patients.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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