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. The objective response rates ranged from 9% to 30% with 3 different PD-1 or PD-1 ligand 1 (PD-L1) inhibitors. The safety profiles were consistent with previous studies of checkpoint inhibitors.
The largest of the trials involved 75 patients with advanced gastric or gastroesophageal junction cancer who received the investigational agent avelumab. Overall, 20 patients received avelumab as second-line therapy and 55 patients received the checkpoint inhibitor as maintenance 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, Yonsei Cancer Center, Shinchon-Dong, South Korea. A majority of patients in both groups had some degree of tumor shrinkage.
The stable disease rates were 35% in the second-line setting and 47% in the maintenance setting.
“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 at 12 weeks,” said Dr Chung.
The median progression-free survival was 11.6 weeks in the second-line setting and 14.1 weeks in the maintenance setting, and the 24-week progression-free survival was 19.3% and 34.0% in the patients receiving second-line therapy and maintenance therapy, 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 cancer, and 18 with gastric cancer. More than 80% of the patients had received ≥2 previous lines of therapy, said Dung T. Le, MD, Assistant Professor of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
Nivolumab treatment resulted in 1 complete response and 7 partial responses, for an overall response rate of 13.6%. The responses had a median duration of 7.1 months. In addition, 11 patients had stable disease, resulting in a disease control rate of 32% (response plus stable disease).
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 patients who received nivolumab had a median overall survival of 5.0 months, a 3-month survival rate of 70%, a 6-month survival rate of 49%, and a 12-month survival rate of 36%.
“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,” said Dr Le.
The smallest of the studies had the highest response rate—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, National Cancer Center East, Chiba, Japan. All but 3 of the patients had received ≥2 previous 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. The median duration of response had not been reached, but it ranged from between 5.5 months and 11.8 months. The median time to progression was 3.7 months.
The 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 those with advanced and previously treated disease. All patients will be screened for PD-L1 expression, according to Dr Doi.
