Adjuvant Chemotherapy with or without Concurrent Radiotherapy for Patients with Stage IB Gastric Cancer: a Subgroup Analysis of the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) Phase III Trial

95 Background: To evaluate the risk of recurrence in patients with pathologically staged Ib, according to the American Joint Committee on Cancer (AJCC) 2002 staging system, gastric cancer (GC) in the phase III adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. Methods: Among 458 GC patients enrolled in ARTIST, 99 had stage Ib (T2N0 or T1N1) disease. Patients were randomly assigned to receive adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n = 50)) or chemoradiotherapy (XPRT, n = 49). Kaplan-Meier method was used to calculate disease-free survival (DFS). Cox proportional hazard models were employed to determine associations between the addition of radiotherapy to XP and DFS after adjustment for patient and disease characteristics. Additionally, analyses were performed according to the AJCC 2010 staging system. Results: With 7 years of follow-up, there were 18 recurrences. The 5-year DFS rates were 88% and 84% in XP and XPRT patients, respectively (P = 0.537). When we reviewed the pathologic stages of the patients according to the AJCC 2010 system, stage migration from Ib to II occurred in 71% of the patients: 98% of the T2N0 patients were reclassified as T3N0, and 42% of the T1N1 patients were reclassified as T1N2. The patients classified as stage Ib according to the AJCC 2002 system and reclassified as stage II exhibited worse, although statistically insignificant, prognosis than the patients who remained in stage Ib (5-year DFS 83% vs. 93%, P = 0.183, HR 1.178, 95% CI 0.420-3.311, P = 0.158). When we compared 5-year DFS in 70 stage II (AJCC 2010 system) patients, the addition of radiotherapy to XP chemotherapy resulted, although again statistically insignificant (P = 0.234), in worse outcome in XPRT arm (77%) than in XPRT arm (88%). Conclusions: This subgroup analysis confirms the clinical relevance of the AJCC 2010 staging system in GC. The role of adjuvant chemotherapy in stage II GC warrants further investigation.

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Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset Analyses

Journal of Clinical Oncology ◽

10.1200/jco.2014.58.3930 ◽

2015 ◽

Vol 33 (28) ◽

pp. 3130-3136 ◽

Cited By ~ 186

Author(s):

Se Hoon Park ◽

Tae Sung Sohn ◽

Jeeyun Lee ◽

Do Hoon Lim ◽

Min Eui Hong ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Adjuvant Chemotherapy ◽

Disease Free Survival ◽

Phase Iii ◽

Adjuvant Chemoradiotherapy ◽

Final Report ◽

D2 Lymph Node Dissection ◽

Node Positive ◽

Stomach Tumors

Purpose The Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial tested whether the addition of radiotherapy to adjuvant chemotherapy improved disease-free survival (DFS) in patients with D2-resected gastric cancer (GC). Patients and Methods Between November 2004 and April 2008, 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 chemoradiotherapy and then two additional cycles of XP (XPRT). This final update contains the first publication of overall survival (OS), together with updated DFS and subset analyses. Results With 7 years of follow-up, DFS remained similar between treatment arms (hazard ratio [HR], 0.740; 95% CI, 0.520 to 1.050; P = .0922). OS also was similar (HR, 1.130; 95% CI, 0.775 to 1.647; P = .5272). The effect of the addition of radiotherapy on DFS and OS differed by Lauren classification (interaction P = .04 for DFS; interaction P = .03 for OS) and lymph node ratio (interaction P < .01 for DFS; interaction P < .01 for OS). Subgroup analyses also showed that chemoradiotherapy significantly improved DFS in patients with node-positive disease and with intestinal-type GC. There was a similar trend for DFS and OS by stage of disease. Conclusion In D2-resected GC, both adjuvant chemotherapy and chemoradiotherapy are tolerated and equally beneficial in preventing relapse. Because results suggest a significant DFS effect of chemoradiotherapy in subsets of patients, the ARTIST 2 trial evaluating adjuvant chemotherapy and chemoradiotherapy in patients with node-positive, D2-resected GC is under way.

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SAMIT: Preliminary safety data from a 2x2 factorial randomized phase III trial to investigate weekly paclitaxel (PTX) followed by oral fluoropyrimidines (FPs) versus FPs alone as adjuvant chemotherapy in patients (pts) with gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.4017 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 4017-4017 ◽

Cited By ~ 3

Author(s):

A. Tsuburaya ◽

K. Yoshida ◽

M. Kobayashi ◽

S. Yoshino ◽

Y. Miyashita ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Safety Data ◽

Phase Iii ◽

Weekly Paclitaxel ◽

Phase Iii Trial ◽

Oral Fluoropyrimidines

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Multicenter phase III trial of adjuvant chemoradiotherapy in stomach tumors 2 (ARTIST 2).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.tps228 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. TPS228-TPS228 ◽

Cited By ~ 4

Author(s):

Se Hoon Park ◽

Su Jin Lee ◽

Seung Tae Kim ◽

Jeeyun Lee ◽

Joon Oh Park ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Statistical Power ◽

Residual Disease ◽

Disease Free Survival ◽

Intestinal Type ◽

Phase Iii ◽

Adjuvant Chemoradiotherapy ◽

Phase Iii Trial ◽

Node Positive ◽

Node Positive Disease

TPS228 Background: Treatment of gastric cancer (GC) has some notable differences between Asia and Western countries including the extent of surgery and the type of adjuvant therapy. In ARTIST trial comparing adjuvant chemotherapy involving capecitabine plus cisplatin with chemoradiotherapy, we reported comparable disease-free survival (DFS) in Korean patients with D2-resected GC. In subset analyses, patients with node-positive disease and intestinal type GC may have benefit with the addition of radiotherapy to adjuvant chemotherapy. Methods: ARTIST 2 (ClinicalTrials.gov, NCT0176146) is a 3-arm, multi-center, open-label phase III trial comparing adjuvant chemotherapy involving S-1 (40 mg/m2 bid 4-weeks-on/2-weeks-off) for one year (arm A) with S-1 plus oxaliplatin (SOX, S-1 40 mg/m2 bid 2-weeks-on/1-week-off plus oxaliplatin 130 mg/m2 iv on day 1) for 8 cycles (arm B) and chemoradiotherapy (arm C). Arm C patients receive SOX for 2 cycles, then concurrent chemoradiotherapy 45 Gy with S-1 40 mg bid daily, followed by additional SOX for 4 more cycles. Patients are randomized 1:1:1 with 3 strata: stage (II or III), type of surgery (subtotal or total gastrectomy) and Lauren classification (diffuse or intestinal type). Eligibility criteria include gastric or gastro-esophageal junction adenocarcinoma, D2 or higher surgery with no residual disease, pathologic stages 2 or 3, lymph node positive disease. Primary endpoint is DFS, and secondary endpoints include overall survival, safety, QOL and molecular biomarkers. To test if experimental arms (arm B or C) lower the hazard of recurrence by 50% (i.e., HR 1.5) compared to arm A, we need 900 patients (300 per arm) with 90% of overall statistical power. First patient entered onto the study in Feb 2013. As of Aug 2014, a total of 118 (13% of target) patients were recruited by 8 Korean tertiary centers. Clinical trial information: NCT0176146.

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