Pembrolizumab Shows Promise for Advanced Esophageal Cancer

The immunotherapy drug pembrolizumab has demonstrated manageable side effects and durable antitumor activity in patients with heavily pretreated, advanced esophageal cancer. These latest findings, from the KEYNOTE-028 trial, were published in the Journal of Clinical Oncology.

A multicohort, phase Ib study in patients with programmed death ligand-1 (PD-L1)—positive advanced solid tumors, previous results from KEYNOTE-028 have shown positive results in small-cell lung cancer. Pembrolizumab is currently approved for certain types of cancers, including as a first-line treatment for metastatic nonsquamous non-small cell lung cancer (NSCLC) and as a treatment for relapsed/refractory Hodgkin lymphoma.

The current study enrolled patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1—positive tumors. Among 83 patients with esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45%) had PD-L1–positive tumors. Twenty-three patients were ultimately enrolled. They received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable side effects. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter.

Median age was 65 years; 78% had squamous histology; and 87% received more than 2 prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months).

The primary end points of the study were safety and overall response rate. Overall response rate was 30% (95% CI, 13% to 53%) and the median duration of response was 15 months (range, 6 to 26 months). The most common side effects were decreased appetite, decreased lymphocyte count, generalized rash, and rash. There were no life-threatening adverse events or deaths were attributed to pembrolizumab.

In May 2017, the FDA halted 3 clinical trials of pembrolizumab for multiple myeloma in response to a pattern of patient deaths. Merck sells the drug under the name Keytruda.