S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: updated results from a phase 3 trial

Seung Tae Kim, Yong Sang Hong, Ho Yeong Lim, Jeeyun Lee, Tae Won Kim, Kyu-Pyo Kim, Sun Young Kim, Ji Yeon Baek, Jee Hyun Kim, Keun-Wook Lee, Ik-Joo Chung, Sang-Hee Cho, Kyung Hee Lee, Sang Joon Shin, Hye Jin Kang, Dong Bok Shin, Jae Won Lee, Sook Jung Jo, Young Suk Park, Seung Tae Kim, Yong Sang Hong, Ho Yeong Lim, Jeeyun Lee, Tae Won Kim, Kyu-Pyo Kim, Sun Young Kim, Ji Yeon Baek, Jee Hyun Kim, Keun-Wook Lee, Ik-Joo Chung, Sang-Hee Cho, Kyung Hee Lee, Sang Joon Shin, Hye Jin Kang, Dong Bok Shin, Jae Won Lee, Sook Jung Jo, Young Suk Park

Abstract

Background: We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer.

Methods: This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed.

Results: The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p = .10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p = .19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment.

Conclusions: Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer.

Trial registration: NCT00677443 and May 12 2008.

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
Kaplan-Meier curves of progression-free survival (PFS) (A) and post-progression- survival (PPS) (B).
Figure 3
Figure 3
Kaplan-Meier curves of overall survival (OS).
Figure 4
Figure 4
Subgroup analysis of overall survival (A) and progression-free survival (B) for the intention to treat population.

References

    1. Schoffski P. The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors. Anticancer Drugs. 2004;15:85–106. doi: 10.1097/00001813-200402000-00001.
    1. Meta-analysis Group In Cancer Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis group in cancer. J Clin Oncol. 1998;16:301–308.
    1. Cascinu S. Oral treatment for gastric cancer: new choices, better choices? Lancet Oncol. 2008;9:188–189. doi: 10.1016/S1470-2045(08)70042-1.
    1. Cervantes A, Roda D, Tarazona N, Rosello S, Perez-Fidalgo JA. Current questions for the treatment of advanced gastric cancer. Cancer Treat Rev. 2013;39:60–67. doi: 10.1016/j.ctrv.2012.09.007.
    1. Pieters A, Laurent S, Dero I, Van Damme N, Peeters M. The role of oral fluoropyrimidines in the treatment of advanced gastric cancer. Acta Gastroenterol Belg. 2008;71:361–366.
    1. Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schoffski P, Sobrero A, Van Cutsem E, Diaz-Rubio E. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004;22:2084–2091. doi: 10.1200/JCO.2004.11.069.
    1. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–2947.
    1. Maehara Y. S-1 in gastric cancer: a comprehensive review. Gastric Cancer. 2003;6(Suppl 1):2–8. doi: 10.1007/s10120-003-0232-9.
    1. Yamada Y, Tahara M, Miya T, Satoh T, Shirao K, Shimada Y, Ohtsu A, Sasaki Y, Tanigawara Y. Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer. Br J Cancer. 2008;98:1034–1038. doi: 10.1038/sj.bjc.6604271.
    1. Zang DY, Lee BH, Park HC, Song HH, Kim HJ, Jung JY, Kim JH, Kim HY, Kwon JH, Hwang SW, Park SR, Park CH, Kim KO, Kim MJ, Jang KM. Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal cancer. Ann Oncol. 2009;20:892–896. doi: 10.1093/annonc/mdn721.
    1. Hong YS, Park YS, Lim HY, Lee J, Kim TW, Kim KP, Kim SY, Baek JY, Kim JH, Lee KW, Chung IJ, Cho SH, Lee KH, Shin SJ, Kang HJ, Shin DB, Jo SJ, Lee JW. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial. Lancet Oncol. 2012;13:1125–1132. doi: 10.1016/S1470-2045(12)70363-7.
    1. Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Rittweger K, Gilberg F, Saltz L. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer. 2011;105:58–64. doi: 10.1038/bjc.2011.201.
    1. Rothenberg ML, Cox JV, Butts C, Navarro M, Bang YJ, Goel R, Gollins S, Siu LL, Laguerre S, Cunningham D. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol. 2008;19:1720–1726. doi: 10.1093/annonc/mdn370.
    1. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–2019. doi: 10.1200/JCO.2007.14.9930.
    1. Lee JL, Kang YK, Kang HJ, Lee KH, Zang DY, Ryoo BY, Kim JG, Park SR, Kang WK, Shin DB, Ryu MH, Chang HM, Kim TW, Baek JH, Min YJ. A randomised multicentre phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Br J Cancer. 2008;99:584–590. doi: 10.1038/sj.bjc.6604536.
    1. Kim GM, Jeung HC, Rha SY, Kim HS, Jung I, Nam BH, Lee KH, Chung HC. A randomized phase II trial of S-1-oxaliplatin versus capecitabine-oxaliplatin in advanced gastric cancer. Eur J Cancer. 2012;48:518–526. doi: 10.1016/j.ejca.2011.12.017.
    1. Seol YM, Song MK, Choi YJ, Kim GH, Shin HJ, Song GA, Chung JS, Cho GJ. Oral fluoropyrimidines (capecitabine or S-1) and cisplatin as first line treatment in elderly patients with advanced gastric cancer: a retrospective study. Jpn J Clin Oncol. 2009;39:43–48. doi: 10.1093/jjco/hyn119.
    1. Shitara K, Sawaki A, Matsuo K, Kondo C, Takahari D, Ura T, Tajika M, Niwa Y, Muro K. A retrospective comparison of S-1 plus cisplatin and capecitabine plus cisplatin for patients with advanced or recurrent gastric cancer. Int J Clin Oncol. 2013;18:539–546. doi: 10.1007/s10147-012-0416-6.
    1. Zhang X, Cao C, Zhang Q, Chen Y, Gu D, Shen Y, Gong Y, Chen J, Tang C. Comparison of the efficacy and safety of S-1-based and capecitabine-based regimens in gastrointestinal cancer: a meta-analysis. PLoS One. 2014;9:e84230. doi: 10.1371/journal.pone.0084230.
    1. Petrelli F, Barni S. Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer. Ann Oncol. 2013;24:186–192. doi: 10.1093/annonc/mds289.
    1. Zietemann VD, Schuster T, Duell TH. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer. J Thorac Dis. 2011;3:88–98.
    1. Hotta K, Kiura K, Fujiwara Y, Takigawa N, Hisamoto A, Ichihara E, Tabata M, Tanimoto M. Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review. PLoS One. 2011;6:e26646. doi: 10.1371/journal.pone.0026646.
    1. Broglio KR, Berry DA. Detecting an overall survival benefit that is derived from progression-free survival. J Natl Cancer Inst. 2009;101:1642–1649. doi: 10.1093/jnci/djp369.
    1. Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26:2006–2012. doi: 10.1200/JCO.2007.14.9898.
    1. Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30. doi: 10.1200/JCO.2004.09.046.
    1. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–237. doi: 10.1200/JCO.2004.05.113.
    1. Yamada Y, Takahari D, Matsumoto H, Baba H, Nakamura M, Yoshida K, Yoshida M, Iwamoto S, Shimada K, Komatsu Y, Sasaki Y, Satoh T, Takahashi K, Mishima H, Muro K, Watanabe M, Sakata Y, Morita S, Shimada Y, Sugihara K. Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2013;14:1278–1286. doi: 10.1016/S1470-2045(13)70490-X.
Pre-publication history
    1. The pre-publication history for this paper can be accessed here:

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner