Among patients who received gastrectomy with D2 lymph node dissection, both adjuvant chemotherapy and chemoradiotherapy were tolerated and equally effective in preventing relapse during seven years of follow-up. However, chemoradiotherapy appeared to benefit patients with node-positive disease or higher lymph node ratio and intestinal-type gastric cancer.
Those are key findings from the final report of the Adjuvant Chemoradiation in Stomach Tumors (ARTIST) trial, which set out to investigate whether adding radiotherapy to adjuvant chemotherapy improved disesase-free survival in patients with D2-resected gastric cancer (GC).
“These long-term results, together with the results from the ACTS-GC and the CLASSIC trials, provide additional support for adjuvant chemotherapy as a standard of care in patients with D2-resected GC,” Dr. Se Hoon Park of Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul, South Korea, and associates, wrote online in the Journal of Clinical Oncology (J. Clin. Onc. 2015 Jan. 5 [doi:10.1200/JCO.2014.58.3930]).
“However, it should be noted that there are subsets of patients who may benefit from the addition of radiotherapy to adjuvant chemotherapy, and the optimal adjuvant chemotherapy regimen has yet to be identified. Thus, adjuvant chemoradiotherapy in node-positive, D2-resected GC should be explored further within the framework of clinical trials.”
For the phase III trial, 458 patients with GC who received gastrectomy with D2 lymph node dissection were randomly assigned to either six cycles of adjuvant chemotherapy with capecitabine and cisplatin (XP) or to two cycles of XP followed by chemoradiation and then two additional cycles of (XPRT). Between November 2004 and April 2008, 228 were assigned to the XP arm and 230 to the XPRT arm (doi:10.1200/JCO.2014.58.3930). Full details of the trial design have been previously published(J. Clin. Ocol. 2012;30:268-73).During a median follow-up of 7 years, the probabilities of disease-free survival at 5 years were 73% in the XP arm and 75% in the XPRT arm, which translated into a hazard ratio of .740. The hazard ratio for overall survival was also similar between the two groups (HR, 1.130). Multivariable analysis revealed that the effect of the addition of radiotherapy on DFS and OS differed by Laurén classification (interactionPvalues of .04 and .03 for DFS and OS, respectively) and by lymph node ratio (interaction Pvalues of less than .01 for both DFS and OS).“Subgroup analyses were performed to identify patient populations who may benefit from chemoradiotherapy, and calculation of HRs and 95% CIs showed that the potential benefit from the addition of radiotherapy to adjuvant chemotherapy could not be excluded in patients with node-positive disease and intestinal-type GC,” the researchers noted. Among 396 patients with node-positive disease, 3-year DFS was significantly different (72% in the XP arm, compared with 76% in XPRT arm; P = .04). Similarly, in 163 patients with intestinal-type GC, 3-year DFS rates were 83% and 94% in the XP and XPRT arms, respectively (P = .01). There also was a trend toward improved DFS in patients with advanced stage.
“At the moment, in making treatment decisions for individual patients, we suggest that advanced stage, lymph node status, and the Lauren classification be the factors taken into account when chemoradiotherapy is being considered,” Dr. Park and associates concluded. “These questions are currently being addressed in our multicenter, larger, three-arm phase III ARTIST 2 trial, which aims to compare all of the current standards of care in the adjuvant setting of D2-resected, node-positive, stage II or III GC (chemotherapy with S-1 for 1 year vs. combination chemotherapy with S-1 and oxaliplatin [SOX] for 6months vs. chemoradiotherapy involving two cycles of SOX followed by S-1/radiotherapy and then four additional cycles of SOX). Issues raised by this ARTIST and other contemporary trials in the adjuvant setting of GC should hopefully be answered by ARTIST 2, where the hypothesis is that the addition of a platinum to S-1 and of radiotherapy to adjuvant chemotherapy will improve DFS. A total of 900 patients (i.e., 300/arm) will be registered onto the ARTIST 2 trial, and the stratification factors include stage, type of surgery, and the Laurén classification.”
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