Sintilimab with CapeOx Demonstrates Promising Efficacy and Manageable Safety Profile as Neoadjuvant Therapy in Patients with Locally Advanced, Resectable Gastric/GEJ Cancer

2021 Year in Review - Gastrointestinal Cancer

Promising response rates were reported in a clinical trial of neoadjuvant sintilimab with CapeOx in patients with resectable, locally advanced gastric/gastroesophageal junction (GEJ) cancer.

Immune checkpoint inhibitors block the action of immune checkpoint proteins such as PD-1, which initiates signaling pathways resulting in the suppression of T-cell antitumor action.1 The use of immune checkpoint inhibitors such as pembrolizumab, ipilimumab, nivolumab, and durvalumab has advanced cancer treatment, but further investigation into their application and combination with other treatment modalities is needed.1 Sintilimab is a selective anti–PD-1 antibody that blocks binding sites to inhibit the interaction of PD-1 and its ligands.1 Jiang and colleagues examined the use of sintilimab plus capecitabine/oxaliplatin (CapeOx) as neoadjuvant therapy in patients with resectable, locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. The results of this phase 2 study were presented at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium virtual meeting.

In this clinical trial, 36 patients with confirmed resectable gastric or GEJ cancer were enrolled. Patients received 3 mg/kg of sintilimab (if their weight was <60 kg) or 200 mg sintilimab (if their weight was ≥60 kg) every 3 weeks. Oxaliplatin 130 mg/m2 was given intravenously on day 1 and oral capecitabine 1000 mg/m2 was given twice a day on days 1 through 14 every 3 weeks. This regimen was administered for 3 cycles, with gastrectomy scheduled for 4 weeks after the last treatment dose. To assess response, tumor imaging was performed at baseline and then again within 1 week before surgery was performed. The primary study end point was pathological complete response.

At data cutoff, 26 patients had received surgery after the neoadjuvant treatment. No serious perioperative complications or mortality were reported. All patients had a complete resection. Of the 26 patients, 25 had completed 3 treatment cycles, with 1 patient only completing 2 cycles because of a grade 3 increase in aspartate transaminase. Six patients had a pathological complete response, 14 patients had a major pathological response, and 3 patients had a partial response. None were found to have disease progression prior to surgery. Positron emission tomography–computed tomography was performed on 18 patients and 11 patients had a partial metabolic response.

Evaluation of treatment-related adverse events (TRAEs) revealed that 25 patients had a TRAE, but most were grade 1 or 2. Hypothyroidism (immune-related TRAE) occurred in 1 patient. Grade 3 TRAEs occurred in 6 patients; 4 patients experienced neutropenia and 1 patient each experienced thrombocytopenia, leukopenia, aspartate aminotransferase increase, and gamma glutamyl transferase increase.

The manageable safety profile of sintilimab with CapeOx makes this a promising therapy for patients with locally advanced, resectable gastric/GEJ cancer.

Source: Jiang H, Yu X, Kong M, et al. Sintilimab plus oxaliplatin/capecitabine (CapeOx) as neoadjuvant therapy in patients with locally advanced, resectable gastric (G)/esophagogastric junction (GEJ) adenocarcinoma. Presented at 2021 ASCO Gastrointestinal Cancers Symposium; January 15-17, 2021; Virtual. Abstract 211.

Reference

  1. Liu X, Yi Y. Recent updates on sintilimab in solid tumor immunotherapy. Biomark Res. 2020;8:69.
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