The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Pembrolizumab monotherapy and pembrolizumab plus chemotherapy prolonged overall survival (OS), but not progression-free survival (PFS), among patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC), according to the results of the phase 3 KEYNOTE-048 trial presented at the ESMO 2018 Congress in Munich, Germany.1

In a press release, Tanguy Seiwert, MD, of the University of Chicago Medicine, Illinois, who is not involved in the trial, commented that “this is the first study to show superior overall survival over the decade-old standard of care, platinum-based chemotherapy and cetuximab.”He further noted that these results “established PD-L1 CPS as a valid marker for head and neck cancer that should be routinely measured in these patients.”

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Investigators of the open-label, phase 3 KEYNOTE-048 trial randomly assigned 882 patients with recurrent/metastatic HNSCC that was not curable with local therapy (but who had not had prior systemic therapy) to receive pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin or carboplatin with 5-fluorouracil), or the standard of care, which is cetuximab plus cisplatin or carboplatin for either 6 cycles, 24 months, disease progression, or until unacceptable toxicity.

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The primary end point was PFS and OS in the overall population and was stratified by PD-L1 combined positive scores (CPS of ≥ 20 and ≥ 1). The data cutoff for this interim analysis was June 13, 2018, and the minimum follow-up was 17 months.

Pembrolizumab monotherapy prolonged OS among patients with PD-L1 tumor expression compared with the standard of care. In the cohort with a CPS of 20 or higher,the median OS with pembrolizumab alone was 14.9 months compared with 10.7 months with standard chemotherapy (hazard ratio [HR], 0.61; 95% CI, 0.45-0.83; P= .0007). The median OS was also prolonged in the cohort with patients with a CPS of 1 or higher, albeit more modestly, with a median OS of 12.3 months with pembrolizumab compared with 10.3 months with chemotherapy (HR, 0.78; 95% CI, 0.64-0.96; P= .0086). In the total population, OS with pembrolizumab was noninferior to chemotherapy.

Pembrolizumab plus chemotherapy significantly prolonged OS in the overall population, but not in the PD-L1–positive cohorts. The median OS for the unselected population was 13.0 months compared with 10.7 months with standard chemotherapy (HR, 0.77; 95% CI, 0.63-0.93; P= .0034). The median OS with pembrolizumab was not superior to standard chemotherapy in the PD-L1 expression cohorts.

Pembrolizumab monotherapy and the pembrolizumab combination with chemotherapy did not significantly improve PFS compared with standard chemotherapy, regardless of PD-L1 expression. 

The ORR was similar between the pembrolizumab plus chemotherapy and chemotherapy arms, at approximately 36% each. The ORR with pembrolizumab monotherapy was lower, at 23%. The median duration of response (DoR), however, was longer when pembrolizumab was part of the regimen. The DoR was 20.9 months with pembrolizumab monotherapy, 6.7 months with pembrolizumab plus chemotherapy, and approximately 4.3 months with standard chemotherapy, regardless of PD-L1 expression.

Grade 3 to grade 5 adverse events (AEs) occurred most frequently with chemotherapy-based regimens, with a rate of 69% with standard chemotherapy and 71% with pembrolizumab plus chemotherapy compared with 17% with pembrolizumab alone. 

These data indicate that “pembrolizumab appears to prolong life even when the cancer continues to grow, suggesting that it should be a first-line therapy in recurrent and metastatic head and neck cancer,” according to Barbara Burtness, MD, of the Yale School of Medicine and Yale Cancer Center in New Haven, Connecticut, and an author of the study.2She noted that “whether pembrolizumab is given alone or with chemotherapy may depend on PD-L1 expression.”

Disclosure: This study was funded by Merck & Co., Inc. For a full list of disclosures, please refer to the study abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO 2018 meeting by visiting the conference page.


  1. Burtness B, et al. KEYNOTE-048: Phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract LBA8_PR.
  2. ESMO. Immunotherapy improves survival in metastatic or recurrent head and neck cancer [press release]. Published October 22, 2018. Accessed October 22, 2018.