Checkpoint Inhibitors Active in Gastric and Esophageal Cancers

Gastrointestinal Cancers Symposium

Immune checkpoint inhibitors demonstrated varying degrees of activity in advanced gastric and esophageal cancers, according to preliminary clinical studies reported at the 2016 Gastrointestinal Cancers Symposium.

Objective response rates ranged from 9% to 30% with 3 different programmed death-1 (PD-1)/ligand 1 (PD-L1) inhibitors. Safety profiles were consistent with prior clinical studies of the checkpoint inhibitor class.

The largest of the trials involved 75 patients with advanced gastric or gastroesophageal junction cancer treated with the investigational agent avelumab. The study population comprised 20 patients who received avelumab as second-line therapy and 55 who received the checkpoint inhibitor as maintenance therapy, irrespective of response to first-line therapy.

As second-line therapy, avelumab led to 3 partial responses, and avelumab maintenance therapy resulted in 1 complete response and 3 partial responses, reported Hyun Cheol Chung, MD, PhD, a medical oncologist at Yonsei Cancer Center, Shinchon-Dong, South Korea. A majority of patients in both groups had some degree of tumor shrinkage.

Stable disease rates were 35% and 47% in the second-line and maintenance settings, respectively.

“Responses were observed in patients with PD-L1–positive and PD-L1–negative tumors, but there was a trend in the second-line population suggesting that PD-L1 expression was associated with increased progression-free survival [PFS] at 12 weeks,� said Chung.

Median PFS was 11.6 weeks with second-line therapy and 14.1 weeks with maintenance therapy, and 24-week PFS was 19.3% and 34.0%, respectively.

A study of nivolumab included 59 patients with previously treated gastroesophageal cancer. The group consisted of 9 patients with advanced esophageal cancer, 31 with gastroesophageal junction disease, and 18 with gastric cancer. More than 80% of the patients had received 2 or more prior lines of therapy, said Dung T. Le, MD, a medical oncologist at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.

Nivolumab treatment resulted in 1 complete response and 7 partial responses for an overall response rate of 13.6%. Responses had a median duration of 7.1 months. Additionally, 11 patients had stable disease, resulting in a disease control rate of 32%.

As in the study reported by Chung, investigators observed a trend toward higher response rate and PD-L1 expression. Tumors exhibiting at least 1% expression had a response rate of 27%, increasing to 33% among tumors with at least 5% PD-L1 expression.

The nivolumab-treated patients had a median overall survival of 5.0 months, 3-month survival of 70%, 6-month survival of 49%, and 12-month survival of 36%.

“We consider the response and survival data encouraging for a chemotherapy-refractory group,� said Le. “We observed responses in patients with PD-L1–positive and PD-L1–negative tumors, even though there was a trend to higher response rates with increased PD-L1 expression.�

The smallest of the studies had the highest response rate, as 7 of 23 patients with previously treated metastatic esophageal cancer had objective responses (all partial responses) with pembrolizumab. Another 2 patients had stable disease, said Toshihiko Doi, MD, PhD, a medical oncologist at the National Cancer Center Hospital East, Chiba, Japan. All but 3 of the patients had received at least 2 prior lines of therapy.

The study included patients with adenocarcinoma and squamous cell carcinoma, and responses were observed in both tumor types. Overall, 12 of the 23 patients had some degree of tumor shrinkage in response to treatment with pembrolizumab. Median duration of response had not been reached but ranged between 5.5 and 11.8 months. The median time to progression was 3.7 months.

Patients included in the analysis were among a larger cohort involved in a broad clinical evaluation of pembrolizumab in advanced solid tumors. On the basis of the “promising� activity demonstrated in the esophageal cancer subgroup, enrollment has begun in a planned 100-patient study of pembrolizumab in patients with advanced and previously treated disease. All patients will be screened for PD-L1 expression, according to Doi.

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