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Randomised phase 3 study of S-1 versus capecitabine, with bevacizumab optional in both arms, in the first-line treatment of metastatic colorectal cancer (mCRC), the SALTO study of the Dutch Colorectal Cancer Group

J.J.M. Kwakman1, L.H.J. Simkens2, J.M. Van Rooijen3, A.J. Van de Wouw4, O.J.L. Loosveld5, G.J.M. Creemers6, M.P. Hendriks7, M. Los8, R.J. Van Alphen9, M.B. Polée10, E.W. Muller11, A.M.T. Van der Velden12, T. Van Voorthuizen13, M. Koopman14, L. Mol15, E. Van Werkhoven16, C.J.A. Punt1

1Academic Medical Center, Medical Oncology, Amsterdam, Netherlands;

2Máxima Medical Center, Medical Oncology, Eindhoven, Netherlands;

3Martini Hospital, Medical Oncology, Groningen, Netherlands;

4VieCuri Medical Center, Medical Oncology, Venlo, Netherlands;

5Amphia Hospital, Medical Oncology, Breda, Netherlands;

6Catharina Hospital, Medical Oncology, Eindhoven, Netherlands;

7Medical Center Alkmaar, Medical Oncology, Alkmaar, Netherlands;

8Sint Antonius Hospital, Medical Oncology, Nieuwegein, Netherlands;

9TweeSteden Hospital, Medical Oncology, Tilburg, Netherlands;

10Medical Center Leeuwarden, Medical Oncology, Leeuwarden, Netherlands;

11Slingeland Hospital, Medical Oncology, Doetinchem, Netherlands;

12Tergooi Hospital, Medical Oncology, Hilversum, Netherlands;

13Rijnstate Hospital, Medical Oncology, Arnhem, Netherlands;

14University Medical Center Utrecht, Medical Oncology, Utrecht, Netherlands;

15Netherlands Comprehensive Cancer Center, Department of Data Management, Nijmegen, Netherlands;

16The Netherlands Cancer Institute, Department of Biometrics, Amsterdam, Netherlands

Background: Hand-foot syndrome (HFS) is a common and troublesome side effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients (pts). The Dutch SALTO study (NCT01918852) was designed to compare the incidence of HFS between S-1 and capecitabine as 1st line treatment in mCRC pts.

Materials and Methods: In this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1:1) with previously untreated mCRC, WHO performance status of 0−2, and planned treatment with

fluoropyrimidine monochemotherapy from 27 hospitals in the Netherlands to receive either capecitabine (1250 mg/m2 for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice-daily on days 1−14) or S-1 (30 mg/m2 twice daily on days 1−14), with bevacizumab co-treatment (7.5 mg/kg on day 1) optional in both arms. Cycles are administered every 3 weeks and treatment is continued until disease progression, unacceptable toxicity, or patients refusal. Randomisation was done centrally by minimisation, with stratification for the use of bevacizumab, WHO performance status, serum lactate dehydrogenase, and institution. The primary endpoint is the incidence of any grade HFS, which is assessed prior to each cycle by local investigators and by patients using a diary. A total of 150 pts is required to demonstrate a difference in HFS of ≥20% with 90% power (α = 0.05, 2-tailed test). Secondary endpoints are grade 3 HFS, other toxicities, progression-free survival (PFS), response rate (RR), overall survival (OS).

Results: Between Jan 30, 2014 and July 14, 2015, we randomly assigned 161 patients with a median age of 73 years to receive either capecitabine (n = 81) or S-1 (n = 80). Co-treatment with bevacizumab was planned in

59% of patients in both arms. Median follow-up is 16.1 months, 20 pts (12%) are still on study. The incidence of any grade HFS as assessed by local investigators is 71% in the capecitabine group and 45% in the S-1 group (p 0.0009), and grade 3 HFS is 21% and 4% (p 0.0029), resp. All grade HFS as assessed by 110 pts (preliminary results) is 76% and 53% (p 0.01), and grade 3 HFS is 18% and 5% (p 0.06). Other grade ≥3 toxicity only differs for anorexia (3% and 13%; p 0.03). No significant differences are observed in RR (42% vs 31%; p 0.19) and PFS (median 8.3 vs 8.4 months; p 0.98). Data on OS are not mature.

Conclusions: Treatment with S-1 results in a significantly lower incidence of HFS compared to capecitabine in pts with mCRC, without compromising efficacy. Updated results will be presented at the meeting.

Conflict of interest: Advisory Board: Punt: Roche, Merck-Serono, Amgen, Bayer, Nordic Pharma; Koopman: Roche, Bayer, Menk, Servier; Van Alphen: Pfizer, Novartis. Corporate-sponsored Research: Koopman: Roche, Bayer, Menk, Servier, Sanofi, Amgen.

 

European Journal of Cancer, Volume 72, Supplement 1, Page S5

© 2017 Elsevier Ltd. All rights reserved.


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