Patients with stage Ib-IVa resectable gastric adenocarcinoma undergoing surgery with curative intent had similar survival outcomes regardless of whether they received chemotherapy or chemoradiotherapy after surgery, according to results of a phase III trial reported at the 2016 World Congress on Gastrointestinal (GI) Cancer.
At a median follow-up of 4.2 years, the 5-year overall survival (OS) was similar between the postoperative chemotherapy and chemoradiotherapy cohorts: 5-year OS rates were 40.8% and 40.9%, respectively (
= .99). Patients in the respective treatment arms demonstrated median survival of 3.5 years versus 3.3 years.
Marcel Verheij, MD, PhD, radiation oncologist at the Netherlands Cancer Institute in Amsterdam presented findings on behalf of the Dutch Colorectal Cancer Group (DCCG) from CRITICS, an international, multicenter, randomized, phase III study.
“The rationale of postoperative chemoradiotherapy after preoperative chemotherapy is to combine systemic and locoregional treatments to reduce the risk of recurrent disease and improve outcomes,” said Verheij.
In CRITICS, patients with stage Ib-IVa resectable gastric adenocarcinoma localized to the stomach or the gastroesophageal junction (N = 788) were randomized upfront to a postoperative regimen and were administered 3 standard courses of epirubicin, cisplatin/oxaliplatin, and capecitabine as preoperative chemotherapy.
Following surgery with curative-intent, patients received either the same chemotherapy (n = 393) or chemoradiotherapy (n = 395) administered at 45 Gy in 25 fractions plus concurrent cisplatin and capecitabine.
“The expected treatment difference in overall survival has not been observed, and the 5-year overall and median survival compare favorably with other studies in Western countries,” said Verheij.
Similar median progression-free survival (PFS) was also observed: Median PFS was 2.3 years with chemotherapy versus 2.5 years with chemoradiotherapy, and 38.5% and 39.5% of patients in the respective treatment arms achieved 5-year PFS.
Although 85% of patients completed the preoperative chemotherapy regimen and 94% of enrolled patients proceeded to surgery, the researchers noted that 52% of patients in the chemotherapy arm and 47% of patients receiving chemoradiotherapy either did not start or complete their full adjuvant regimen.
The most frequently cited reasons for noncompliance in the chemotherapy and chemoradiotherapy arms, respectively, included patient refusal (8% vs 6%), progressive disease (8% vs 4%), postoperative complication (2% vs 5%), or toxicity from preoperative chemotherapy, accounting for 4% of patients in both postsurgical arms. Preoperative grade 3 /4 toxicities included neutropenia, diarrhea, and nausea. Grade 5 cardiovascular, GI, and infectious toxicities were reported in 12 patients.
Surgery-related complications occurred in 145 (22%) of patients, and in-hospital deaths were reported for 15 (2%) patients.
Verheij said that surgical quality was excellent, with 87% of patients undergoing at least a D1+ dissection without splenectomy or pancreatectomy and removal of a median of 20 lymph nodes. “The surgical quality in this study addressed important shortcomings of previous studies, and adequate surgery remains the cornerstone of treatment in this setting,” he commented.
Grade III or higher hematologic toxicity occurred in 44% of patients in the chemotherapy only arm, versus 34% among those in the chemoradiotherapy arm (P = .01), withGI toxicity occurring more frequently in the latter group (42%), versus 37% in the chemotherapy-only arm (P
“Based on the currently available data, no advice can be given on the preferred adjuvant strategy; as less that 50% of patients could complete full treatment, more emphasis on preoperative strategies, when patients may better tolerate treatment, should be considered,” Verheij said.
Dirk Arnold, MD, PhD, from the Instituto CUF de Oncologia in Lisbon, Portugal, said in a statement that focus should be on preoperative therapy: “It is well known that only a limited number of patients are good candidates for any postoperative treatment following gastrectomy, so any postoperative treatment intensification may not be the right strategy.”
“Despite the identification of subgroups benefitting from this approach with postoperative chemoradiation, the strategy should prompt an intensification of the preoperative treatment, and already other trials are evaluating different approaches, including chemoradiation in this setting, compared to standard chemotherapy alone,” Arnold continued.
Verheij said that an analysis is ongoing to identify treatment benefits in specific subgroups and that the planned CRITICS II randomized phase II study will evaluate chemotherapy, chemoradiotherapy, and combined chemo-radiotherapy in the preoperative setting.
Verheij M, Cats A, Jansen EP, et al. A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: first results from the CRITICS study. Presented at: 2016 World Congress on GI Cancer; June 28 - July 2, 2016; Barcelona, Spain. Abstract LBA-02.
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