San Francisco, CA—Although immunotherapy drugs targeting programmed cell death-1 (PD-1) have proved to be effective in patients with melanoma and lung cancer, new data from 2 recent studies suggest that these drugs may also be effective in patients with certain gastrointestinal cancers.1,2 In the first study, Dung Thi Le, MD, Assistant Professor of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, and colleagues explored the outcomes of patients with gastric or gastroesophageal cancer (GC/GEC) receiving nivolumab. In the second study, Toshihiko Doi, MD, PhD, National Cancer Center Hospital East, Chiba, Japan, and colleagues explored the safety and efficacy of pembrolizumab in patients with esophageal carcinoma. Both studies showed encouraging antitumor activity, and the results were presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA.
Patients with metastatic, histologically confirmed GC/GEC were assigned to receive intravenous nivolumab (3 mg/kg), and were treated until disease progression or intolerable toxicity. The primary end point was objective response rate (ORR); other end points included safety, progression-free survival, overall survival (OS), and biomarker status.
Fifty-nine patients with a median age of 60 years were treated with a median of 4 doses (range, 1-25) of single-agent nivolumab; 83% of them had received ≥2 prior regimens. ORR was 12% (n = 7/58; 1 complete and 6 partial responses), and 12 (21%) patients had stable disease. The median duration of response was 7.1 months (95% CI, 3.0-13.2). Median OS was 6.8 months (95% CI, 3.3-12.4), and the 12-month OS rate was 38% (95% CI, 23.2-52.7). A total of 39% of tumor samples were programmed death-ligand 1 (PD-L1)–positive. In patients with PD-L1–positive and –negative tumors, ORRs were 18% and 12%, respectively. Treatment-related adverse events (TRAEs) occurred in 66% of patients; most were grade 1/2. Grade 3/4 TRAEs occurred in 14% of patients; these included pneumonitis, fatigue, diarrhea, vomiting, and hypothyroidism. No treatment-related deaths occurred.
Dr Le and colleagues concluded that nivolumab monotherapy was well tolerated and showed favorable antitumor activity in heavily pretreated patients with GC/GEC.
Patients received pembrolizumab 10 mg/kg every 2 weeks for ≤2 years. Their responses were assessed every 8 weeks for the first 6 months, and then every 12 weeks; the primary end point was ORR. The patients’ median age was 65 years, and of the 23 enrolled, 82.6% were men and 87.0% had received ≥2 prior therapies for metastatic disease. The median follow-up duration was 31 weeks as of the August 2015 data cutoff date. Nine (39.1%) patients experienced TRAEs, with the most common being decreased appetite (n = 3; 13.0%), and 4 (17.4%) patients experienced grade 3 TRAEs, with decreased lymphocytes reported in 2 (8.7%) patients. No patients died or discontinued pembrolizumab as a result of a TRAE. Immune-mediated adverse events included grade 2 hypothyroidism (n = 2; 8.7%) and adrenal insufficiency (n = 1; 4.3%). ORR was 30.4% (95% CI, 13.2-52.9), and the stable disease rate was 13.0% (n = 3; 95% CI, 2.8-33.6).
“Pembro[lizumab] continued to show manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1−positive advanced esophageal carcinoma,” Dr Doi and colleagues concluded.
1. Le DT, Bendell JC, Calvo E, et al. Safety and activity of nivolumab monotherapy in advanced and metastatic (A/M) gastric or gastroesophageal junction cancer (GC/GEC): results from the CheckMate-032 study. Presented at: 2016 Gastrointestinal Cancers Symposium; January 21, 2016; San Francisco, CA.
2. Doi T, Piha-Paul SA, Jalal SI. Updated results for the advanced esophageal carcinoma cohort of the phase Ib KEYNOTE-028 study of pembrolizumab (MK-3475). Presented at: 2016 Gastrointestinal Cancers Symposium; January 21, 2016; San Francisco, CA.