Abstract
BackgroundNivolumab monotherapy has demonstrated superior efficacy in advanced unresectable gastric cancer (GC), but its impact on resectable GC remains unknown. This phase I study aimed to evaluate safety, feasibility, and potential biomarkers of neoadjuvant nivolumab monotherapy in resectable GC.MethodsUntreated, resectable, cT2 or more advanced gastric adenocarcinomas with clinical stage I, II, or III were treated with two doses of nivolumab before gastrectomy. Patients were excluded if their tumors may be applicable to neoadjuvant chemotherapy. The primary endpoint was the incidence of adverse event (AE) categories of special interest.ResultsAll of the 31 enrolled patients completed 2 doses of nivolumab monotherapy. While 30 (97%) patients underwent surgery with curative intent, 1 patient discontinued before the planned surgical intervention because of a newly emerging liver metastasis. Seven patients (23%) had nivolumab treatment-related AEs, and one patient had a treatment-related AE of grade 3–4. The incidences of treatment-related AE categories of special interest ranged from 0 to 6%. Notable surgical complications included two cases of grade 3 anastomotic leakage and two cases of pancreatic fistula. The major pathologic response (MPR) assessed by the independent pathology review committee was achieved in five (16%) patients, of which one patient had a pathologic complete response. The MPR was mostly observed in patients with positive PD-L1 expression, high microsatellite instability, and/or high tumor mutation burden.ConclusionsNeoadjuvant nivolumab monotherapy is feasible with an acceptable safety profile and induces a MPR in certain patients with resectable GC. (Registration: clinicaltrials.jp, JapicCTI-183895).
Highlights
Gastric cancer (GC) is one of the most common cancers in the world, with more than 1 million new incidences and approximately 770,000 deaths in 2020 [1]
This study is a part of the ONO-4538-67 study (JapicCTI-183895), which is a multicenter, open-label, singlearm phase I trial of neoadjuvant nivolumab monotherapy for resectable malignancies of gastric cancer (GC) or non-small-cell lung cancer (NSCLC) in Japan
When the true incidence of the adverse event (AE) categories of special interest in this neoadjuvant nivolumab monotherapy was postulated as 3%, 5%, and 7%, at least 1 among the 30 patients might have experienced these AEs with a probability of 59.9%, 78.5%, and 88.6%, respectively
Summary
Gastric cancer (GC) is one of the most common cancers in the world, with more than 1 million new incidences and approximately 770,000 deaths in 2020 [1]. Asian investigators have been keen to explore neoadjuvant chemotherapy, which has potential benefits in terms of early exposure of potential micrometastases to cytotoxic agents in addition to the likelihood of tumor shrinkage. These attempts have shown safety with a high compliance to the preoperative treatment in addition to down-staging and a high R0 resection rate in the neoadjuvant treatment arm [5]. The establishment of optimal biomarkers can justify the delivery of this relatively less toxic treatment for selected patients We conducted this phase I study to assess the safety and feasibility of neoadjuvant nivolumab monotherapy in patients with resectable GC. The correlations between conventional biomarkers and the clinical response were evaluated
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