Nivolumab Active in Heavily Pretreated Esophageal Cancer

Published: Friday, Jan 22, 2016

The immune checkpoint inhibitor nivolumab demonstrated activity in patients with previously treated esophageal cancer, Japanese investigators reported at the 2016 Gastrointestinal Cancers Symposium in San Francisco.

Overall, 11 of 64 patients had objective responses, and 16 others had stable disease. Responses had a median duration of 92 days and a maximum of 205 days.

Approximately half of the patients had some degree of tumor shrinkage in response to treatment with nivolumab, reported Takahashi Kojima, MD, a medical oncologist at the National Cancer Center Hospital East in Kashiwa, Japan. The treatment was generally well tolerated and associated with a low rate of grade 3/4 gastrointestinal and hepatobiliary adverse events.

“The level of activity observed in this preliminary trial warrants further investigation, and a phase III trial of nivolumab as second-line therapy in advanced esophageal cancer has begun,” said Kojima.

Nivolumab is a human monoclonal antibody against PD-L1 and inhibits binding of both PD-L1 and PD-L2. More than 40% of esophageal cancers express PD-L1/L2, and ligand expression has been associated with poor prognosis.

Kojima reported findings from a phase II trial of nivolumab in patients with squamous-histology esophageal cancer that had progressed during or after treatment with at least one prior systemic regimen (range 1 to >4 prior regimens). The trial had a primary endpoint of objective response by independent review. Secondary endpoints included investigator-assessed objective response, overall survival (OS), progression-free survival (PFS), and disease control rate.

Patients received nivolumab 3 mg/kg every 2 weeks by intravenous infusion, and treatment continued until disease progression or development of unacceptable toxicity.

The study involved a heavily pretreated cohort, as two thirds of the patients had received 3 or more prior systemic regimens, two thirds had prior surgical resection, and two thirds had a history of radiation therapy. The patients had a median age of 62, men accounted for 81% of the patient population, and more than half of the patients had ECOG 1 performance status.

By independent review, one patient achieved a complete response to treatment with nivolumab, and 10 had partial responses, resulting in an overall response rate of 17.2%. By investigator assessment, 2 patients had complete responses, and 12 had partial responses, yielding a total response rate of 22%.

Additionally, 16 (25%) patients had stable disease by independent review and 20 (31.3%) by investigator assessment. The clinical benefit rates were 42% and 53%, respectively.

Among responding patients, the median time to response was 44 days, and the time to response onset ranged from 43 to 85 days.

The cohort had a median OS of 10.78 months and a median PFS of 1.51 months.

The most frequently reported all-grade adverse events (AEs) were diarrhea (20%), decreased appetite (20%), lung infection (12.3%), fatigue (12.3%), rash (10.8%), and constipation (10.8%). The most common grade 3/4 AEs were lung infection (9.2%) and decreased appetite (3.15). Serious AEs included lung infection (6.2%, drug-related in half of cases), dehydration (4.6%, drug-related in two of three cases), and interstitial lung disease (3.1%, drug-related in both cases).

“Drug-related interstitial lung disease was reported in five patients, and four of these patients recovered or improved with supportive care,” he added. “One patient had not recovered as of data cutoff.”

“Nivolumab monotherapy in Japanese esophageal cancer patients was effective, Kojima concluded, “and patients who were considered to have a complete response or partial response had durable responses.”


Kojima T, Hara H, Yamaguchi K, et al. Phase II study of nivolumab (ONO-4538/BMS-936558) in patients with esophageal cancer: preliminary report of overall survival. J Clin Oncol. 34, 2016 (suppl 4S; abstr TPS175).

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