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.