Immunotherapy in Advanced Esophageal Carcinoma

Key Points

  • Response to pembrolizumab was observed in 30% of patients with advanced esophageal carcinoma.
  • The median duration of response was 15 months.

As reported in the Journal of Clinical Oncology by Doi et al, pembrolizumab (Keytruda) showed activity in patients with previously treated advanced esophageal carcinoma in the phase Ib multicohort KEYNOTE-028 study.

Study Details

In the study, eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction with failure of standard therapy and programmed cell death ligand 1 (PD-L1)–positive tumors received pembrolizumab at 10 mg/kg every 2 weeks for up to 2 years or until disease progression or unacceptable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter.

Among 83 patients with samples evaluable for PD-L1 expression, 37 (45%) had PD-L1–positive tumors; of them, 23 were enrolled. The median age of patients was 65 years, 78% had squamous histology, and 87% had received at least two prior therapies for advanced or metastatic disease.

Responses

The median follow-up at data cutoff in February 2017 was 7 months (range = 1–33 months). Partial responses were observed in seven patients (30%). Response was observed in 5 of 18 patients (28%) with squamous histology and 2 of 5 patients (40%) with adenocarcinoma. A decrease in target lesion burden was observed in 12 patients (52%).

The median time to response was 4 months. The median duration of response was 15 months (range = 6 to ≥ 26 months).

The median progression-free survival was 1.8 months, with 6- and 12-month rates of 30% and 22%, respectively. The median overall survival was 7.0 months, with 6- and 12-month rates of 60% and 40%, respectively. A higher score on a 6-gene interferon-γ gene-expression signature (CXCL9, CXCL10, HLA-DRA, IDO1, IFNG, and STAT1) was associated with a trend toward improved progression-free survival (P = .053) and response rate (P = .107).

Adverse Events

Treatment-related adverse events occurred in 39% of patients, with the most common being rash (13%) and decreased appetite and decreased lymphocyte count (9% each). Grade 3 treatment-related adverse events (no grade 4 events were observed) occurred in four patients (17%), including decreased lymphocyte count (9%) and decreased appetite, liver disorder, and generalized rash (4% each). Potentially immune-related events occurred in six patients (26%), including hypothyroidism in two (9%) and adrenal insufficiency, enterocolitis, hyperthyroidism, and generalized rash in one (4%) each.

The investigators concluded: “Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1–positive advanced esophageal carcinoma.”

The study was supported by Merck.

Toshihiko Doi, MD, PhD, of the National Cancer Center East, Kashiwa, Japan, is the corresponding author of the Journal of Clinical Oncology article. 

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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