Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial)

Abstract

Background

In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin.

Patients and methods

This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m2/day on days 1–14; oxaliplatin 130 mg/m2 on day 1; every 3 weeks) or SP (S-1 80 mg/m2/day on days 1–14; cisplatin 60 mg/m2 on day 1; every 3 weeks [SP3]).

Results

Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67–1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66–1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX.

Conclusions

SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC.

Trial registration

ClinicalTrials.gov: NCT01671449

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Acknowledgements

The authors thank all patients and investigators who participated in this study. They also thank Jeil Pharmaceutical Co., Ltd (Korea) for the supply of oxaliplatin.

Funding

This study was partly supported by Jeil Pharmaceutical Co., Ltd. This was an investigator-initiated trial. The company had no role in the interpretation of data or the preparation, review, or approval of the manuscript, or decision to submit the study for publication. The corresponding author had full access to all study data and was responsible for the final decision to submit for publication.

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Correspondence to Min-Hee Ryu or Young Iee Park.

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Conflict of interest

K-WL reported honorarium from Bristol Myers Squibb, Eli Lilly, and Genexine, outside the submitted work; advisory role with Bayer outside the submitted work; and research funding from AstraZeneca/MedImmune, ASLAN pharmaceuticals, Array BioPhrama, ALX Oncology, BeiGene, Daiichi Sankyo, Five Prime Therapeutics, Green Cross, LSK BioPharma, MacroGenics, Merck KGaA, Merck Sharp & Dohme, Ono Pharmaceutical, Pharmacyclics, Pfizer, Taiho Pharmaceutical, and Zymeworks to his institution (for conducting clinical trials), outside the submitted work. M-HR reported honorarium or advisory role with ONO Pharmaceutical, Bristol Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Taiho, Novartis, and Daehwa Pharmaceutical, outside the submitted work. Y-KK reported advisory role with Ono Pharmaceutical, Bristol Myers Squibb, Amgen, Daehwa Pharmaceutical, ALX Oncology, Zymeworks, Novartis, Macrogenics, and Surface Oncology, outside the submitted work. All the remaining authors (I-JC, YIP, B-HN, H-SO, KHL, HSH, B-GS, J-CJ, HRL, JWK, SRP, and SHC) have declared no conflicts of interest.

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Lee, K., Chung, I., Ryu, M. et al. Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial). Gastric Cancer (2020). https://doi.org/10.1007/s10120-020-01101-4

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Keywords

  • Gastric cancer
  • S-1
  • Oxaliplatin
  • Cisplatin
  • Phase III
  • Chemotherapy