Abstract 2117
Background
S-1 is a commonly used agent in first line therapy of advanced gastric cancer in Japan. The recommended initial dose of S-1 is 120 mg/day for patients (pts) with a body surface area (BSA) of ≥ 1.5 m2 in Japan. Systemic exposure to 5-FU is significantly lower in Japanese cancer pts with a large BSA of ≥ 1.75 m2 who received the recommended fixed dose of S-1, as compared with those with a BSA of ≥ 1.50 m2 and <1.75 m2 (Ann Oncol 20: 946-949, 2009). However, there has been little knowledge of the relationship between survival and fixed dosing of S-1 in pts with large BSA.
Methods
Actual data from four randomized Japanese Phase III trials [START (S-1 vs S-1/docetaxel), SPIRITS (S-1 vs S-1/cisplatin), GC0301/TOP-002 (S-1 vs S-1/irinotecan), G-SOX (S-1+cisplatin vs S-1/oxaliplatin)] were combined to evaluate the effect of BSA on survival (OS) in terms of S-1 monotherapy and S-1 combination therapy. The pts were divided into two categories: those with BSA of ≥ 1.50 m2 and <1.75 m2 and those with a BSA of ≥ 1.75m2. The prognostic relevance of BSA was assessed using a multivariate proportional hazards model adjusted for the established clinical prognostic factors including age, performance status, tumor status, primary tumor, hematogenous metastasis, and peritoneal metastasis.
Results
A total of 1,246 pts were available in this analysis (S-1 monotherapy, n = 395; S-1 combination therapy, n = 851). The median OS for S-1 monotherapy and S-1 combination therapy was 11.7 and 13.6 months, respectively. In pts treated with S-1 monotherapy, OS was significantly shorter in those with a BSA of ≥ 1.75 m2, compared with those with a BSA of ≥ 1.5 m2 and <1.75m2 (HR 1.39; 95% CI 1.05-1.84; p = 0.02). However, OS was comparable in the two BSA categories for pts treated with S-1 combination (HR 1.09; 95% CI 0.90-1.34; p = 0.349). BSA was an independent prognostic factor in S-1 monotherapy (HR 1.33; 95% CI 0.999-1.77; p = 0.05) but not in S-1 combination therapy (HR 1.05; 95% CI 0.85-1.29; p = 0.65).
Conclusions
Although the fixed dosing of S-1 monotherapy affects the survival in pts with large BSA, combination therapy might overcome the worse prognosis even in those with large BSA.
Clinical trial identification
UMIN000019519.
Editorial acknowledgement
Legal entity responsible for the study
Japan Clinical Cancer Research Organization.
Funding
Has not received any funding.
Disclosure
W. Ichikawa: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (institution): Takeda Pharmaceutical Co.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd.; Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Shionogi Pharmaceutical Co. Ltd. Y. Sunakawa: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Taiho Pharmaceutical Co. Ltd; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Yakult Honsha Co. Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd; Honoraria (self), Research grant / Funding (institution): Sanofi K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Daiichi Sankyo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Dainippon Sumitomo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Solasia Pharma K.K. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Honoraria (institution), Advisory / Consultancy: Astellas Pharma; Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (institution): Medi Science. K. Oba: Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi-Sankyo Pharmaceutical Co., Ltd.; Honoraria (self): Asahi Kasei Pharma Corp.; Advisory / Consultancy: Takeda Pharmaceuticals, Co., Ltd.; Advisory / Consultancy: Ono Pharmaceutical Co., Ltd. Y. Yamada: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Nippon Kayaku; Honoraria (self): Eli Lilly; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi-Sankyo. Y. Sakata: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Advisory / Consultancy: Yakult Honsha. M. Takeuchi: Advisory / Consultancy: Hisamitsu Pharmaceutical; Advisory / Consultancy: Kowa; Advisory / Consultancy: Shionogi; Advisory / Consultancy: AbbVie. M. Fujii: Travel / Accommodation / Expenses: Taiho Pharmaceutical Co. Ltd.; Travel / Accommodation / Expenses: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.
Resources from the same session
3034 - Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL STUDY
Presenter: Maria Agnese Fabbri
Session: Poster Display session 2
Resources:
Abstract
4772 - Real world comparison of the impact of adjuvant capecitabine in women with high-risk triple-negative breast cancer after neoadjuvant chemotherapy
Presenter: Maysa Vilbert
Session: Poster Display session 2
Resources:
Abstract
5627 - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals
Presenter: Sabela Recalde
Session: Poster Display session 2
Resources:
Abstract
3917 - Impact of delayed neoadjuvant systemic chemotherapy on survival among breast cancer patients
Presenter: Mariana Chavez Mac Gregor
Session: Poster Display session 2
Resources:
Abstract
2246 - Clinical Confirmation of Higher Exposure to Niraparib in Tumor vs Plasma in Patients With Breast Cancer
Presenter: Laura Spring
Session: Poster Display session 2
Resources:
Abstract
581 - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index
Presenter: Mohammad Hojouj
Session: Poster Display session 2
Resources:
Abstract
5327 - Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
Presenter: Silvia Mihaela Ilie
Session: Poster Display session 2
Resources:
Abstract
3613 - Pre-specified interim analysis of the SAFE trial (NCT2236806): a 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab.
Presenter: Lorenzo Livi
Session: Poster Display session 2
Resources:
Abstract
3736 - Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-center comparative study.
Presenter: Icro Meattini
Session: Poster Display session 2
Resources:
Abstract
5085 - Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
Presenter: Isabel Blancas López-Barajas
Session: Poster Display session 2
Resources:
Abstract