Pembrolizumab in Pretreated Advanced Esophageal Adenocarcinoma or Squamous Cell Carcinoma


Key Points

  • The objective response rate among all patients was 9.9%.
  • Median duration of response was not reached at time of analysis.

As reported in JAMA Oncology by Shah et al, the phase II KEYNOTE-180 trial has shown that pembrolizumab produces durable responses in some patients with pretreated locally advanced or metastatic esophageal adenocarcinoma or squamous cell carcinoma.

Study Details

In the trial, 121 patients with disease progressing after ≥ 2 lines of systemic therapy were enrolled from 57 sites in 10 countries between January 2016 and March 2017. Pembrolizumab was given at 200 mg every 3 weeks until disease progression, unacceptable toxic effects, or study withdrawal for up to 2 years.

The primary endpoint was objective response rate on RECIST criteria on central imaging review.

Response Rates

The median duration of follow-up was 5.8 months. Objective response was achieved in 12 patients (9.9%), with median duration of response not being reached at time of analysis (range = 1.9–14.4 months). Objective response rates were 14.3% among 63 patients with squamous cell carcinoma, 5.2% among 58 patients with adenocarcinoma, 13.8% among 58 patients with programmed death ligand-1 (PD-L1)–positive tumors (combined positive score ≥ 10 on immunohistochemistry), and 6.3% among 63 patients with PD-L1–negative tumors.  

Adverse Events

Treatment-related grade ≥ 3 adverse events were observed in 15 patients (12.4%). Adverse events led to treatment discontinuation in 5 patients (4.1%). Immune-mediated adverse events occurred in 25 patients (20.7%), with grade ≥ 3 events in 7 (5.8%). Treatment-related pneumonitis resulted in death in 1 patient. 

The investigators concluded, “Where effective treatment options are an unmet need, pembrolizumab provided durable antitumor activity with manageable safety in patients with heavily pretreated esophageal cancer. Phase III studies evaluating pembrolizumab vs standard therapy for patients with esophageal cancer progressing after first-line therapy or in combination with chemotherapy as first-line therapy for patients with locally advanced unresectable or metastatic esophageal cancer are ongoing.”

Manish A. Shah, MD, of Weill Cornell Medical College, NewYork-Presbyterian Hospital, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Merck & Co Inc. The study authors’ full disclosures can be found at

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®.