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
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract