Impact of progression type on overall survival in patients with advanced gastric cancer based on randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin

4540 Background: Up to now the value of 2nd-line therapy for metastatic gastric cancer is unclear. So far there are no randomized phase III data comparing 2nd-line chemotherapy to BSC. Irinotecan has proven activity in 1st-line therapy. In this randomized phase III study we compared irinotecan to BSC to evaluate the value of 2nd- line chemotherapy for gastric cancer. Methods: Prospective multicenter randomized phase III study, open label. Eligibility: Metastatic or locally advanced gastro-esophageal junction or gastric adenocarcinoma. Objective tumor progession (PD) within 6 months after 1st- line chemotherapy. ECOG PS 0–2. Statistics: Primary endpoint: Overall survival (OS). Hypothesis: H1: OS(Irinotecan)>OS(BSC). Calculated number of pts needed (power 80%, alpha error 5%): 60 pts per arm. Stratification for a) PD less versus (vs) more than 3 months after 1st line chemotherapy, b) ECOG PS 0/1 vs 2. Treatment: Arm A: Irinotecan 250mg/m2 q3w (1st cycle) to be increased to 350 mg/m2, depending on toxicity. Arm B: BSC Results: Between Oct 2002 and Dec 2006 40 pts were randomized. The study was closed prematurely due to poor accrual. Arm A:21 pts, arm B 19 pts. Median age A: 58 yrs (43–73), B: 55 yrs (35–72); PD less vs more than 3 months after 1st-line chemotherapy: A: 18 / 3, B: 17 / 2pts. ECOG PS 0/1 vs 2: A: 17/ 4, B: 14/ 5pts. Pre-treatment with cisplatin: A: 21, B:19 pts. Arm A: 68 cycles administered in 21 pts. Toxicity: (main CTC grade 3/ 4): Nausea 1 pt, vomiting 1 pt, diarrhoea: 5 pts, neutropenic fever: 2 pts, data incomplete 6 pts. In 37% of 19 evaluable pts irinotecan dose was escalated to 350mg/m2. Response (19 pts evaluable): No objective responses, SD 58%, PD 42%. Improvement of tumor related symptoms: 44% of pts in arm A, 5% in arm B. Survival: (evaluable pts arm A 21, arm B 18): median survival arm A: 123 days (95%CI 95–216), arm B 72.5 days (95%CI 41–106); OS: HR=2.85 (95%CI 1.41–5.79), Logrank test (two-sided): p=0.0027. Conclusions: To our knowledge this is the first randomized phase III study investigating 2nd- line chemotherapy in gastric cancer. Irinotecan as 2nd-line chemotherapy significantly prolongs overall survival compared to BSC. 2nd-line chemotherapy can now be considered as a proven option in gastric cancer. [Table: see text]

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Randomized phase III study of S-1 alone versus S-1 plus docetaxel (DOC) in the treatment for advanced gastric cancer (AGC): The START trial update.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.4016 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 4016-4016 ◽

Cited By ~ 7

Author(s):

M. Fujii ◽

Y. H. Kim ◽

T. Satoh ◽

H. Hosaka ◽

T. Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Phase Iii ◽

Phase Iii Study ◽

Start Trial

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The Chinese subgroup from a randomized phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone as second-line treatment of HER2-amplified advanced gastric cancer (AGC) in Asian countries.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4109 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4109-4109 ◽

Cited By ~ 1

Author(s):

Guo-ping Sun ◽

Yan Sun ◽

Rui-hua Xu ◽

Jian-Ming Xu ◽

Jin Li ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Regional Differences ◽

Mainland China ◽

Progression Free Survival ◽

Phase Iii ◽

Weekly Paclitaxel ◽

Phase Iii Study ◽

The Impact ◽

Chinese Subjects

4109 Background: TyTAN is a randomized phase III study to evaluate lapatinib (L) plus paclitaxel (P) in pretreated HER2 amplified (HER2+) advanced gastric cancer (AGC). The disease characteristics and GC treatment pattern differed in Japan and in China, so a subgroup analysis was done for subjects recruited in mainland China. Methods: AGC subjects with prior 5-FU and/or cisplatin and HER2 amplification by fluorescence in situ hybridization (FISH) in tumor tissue were randomized 1:1 to L (1500mg QD) and P (80mg/m2, Day 1, 8, 15 q4w) or P alone (80mg/m2, Day 1, 8, 15 q4w). 1st endpoint was overall survival (OS). 2nd endpoints included progression free survival (PFS), overall response rate (ORR) and safety. A total of 95 subjects recruited from mainland China. Results: TyTAN was not significant in OS (HR0.84), but 2 months OS improvement was observed in L+P arm. The results from Chinese subgroup are shown in the Table. The most common adverse events in Chinese subjects were similar as in whole population (neutropenia, diarrhea, rash, leukopenia, anemia, fatigue). Compare to the overall results, less Chinese subjects reported nausea and vomiting. Conclusions: This analysis showed that there were clear regional differences as observed between subjects in China and Japan. The addition of L to P was associated with a clinically meaningful benefit in subjects recruited from mainland China. These data warrants further prospective evaluations on the impact of regional differences in the outcome of HER+ GC in East Asian patients. Clinical trial information: NCT00486954. [Table: see text]

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Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.119 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 119-119 ◽

Cited By ~ 1

Author(s):

Jin Matsuyama ◽

Yukinori Kurokawa ◽

Kazuhiro Nishikawa ◽

Yutaka Kimura ◽

Atsushi Takeno ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Advanced Gastric Cancer ◽

Peritoneal Metastasis ◽

Oral Intake ◽

Hazard Ratio ◽

Phase Iii ◽

Her2 Positive ◽

Eligibility Criteria ◽

Phase Iii Study

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.

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Chemotherapy for advanced gastric cancer: ongoing phase III study of S-1 alone versus S-1 and docetaxel combination (JACCRO GC03 study)

International Journal of Clinical Oncology ◽

10.1007/s10147-008-0775-1 ◽

2008 ◽

Vol 13 (3) ◽

pp. 201-205 ◽

Cited By ~ 19

Author(s):

Masashi Fujii

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Phase Iii ◽

Phase Iii Study ◽

Ongoing Phase

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Randomized phase III study of S-1 alone versus S-1 + cisplatin in the treatment for advanced gastric cancer (The SPIRITS trial) SPIRITS: S-1 plus cisplatin vs S-1 in RCT in the treatment for stomach cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4514 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4514-4514 ◽

Cited By ~ 29

Author(s):

H. Narahara ◽

W. Koizumi ◽

T. Hara ◽

A. Takagane ◽

T. Akiya ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Primary Endpoint ◽

Standard Treatment ◽

High Response Rate ◽

Phase Iii ◽

Rank Test ◽

Open Label ◽

Eligibility Criteria ◽

Phase Iii Study

4514 Background: S-1 has been widely used against advanced gastric cancer (AGC) not only as monotherapy but also in combination with other cytotoxic compounds. Results of a phase I/II study combining S-1 + cisplatin (CDDP) were very encouraging with a high response rate (RR) of 76%, and the MST (Median Survival Time) of 383 days (Koizumi W et al, Br J Cancer, 2003). Based on these results, a phase III study comparing S-1 alone with S-1 + CDDP has been conducted to further evaluate the efficacy and safety for S-1 + CDDP as a standard treatment for AGC. Methods: This is a randomized, controlled, open-label, parallel, multicenter study. Patients (pts) are randomized to one of two treatment arms. Arm A: Pts receive oral S-1 (40 mg/m2) twice daily 28 days followed by 14 days rest. Arm B: Pts receive oral S-1 (40 mg/m2) twice daily 21 days followed by 14 days rest plus CDDP (60 mg/m2) iv on day 8. Eligibility criteria included unresectable/recurrent AGC, age 20–74, no prior chemotherapy for AGC. Primary endpoint was overall survival (OS). Main secondary endpoints included RR, time to treatment failure (TTF) and toxicity. Based on planned sample size of 284 pts, the trial was designed to have 90% power to detect an improvement in median OS from 8 to 12 months (2-sided log-rank test; significance level 0.05). Results: 305 pts (Arm A/B, 152/153) were randomized between Mar 2002 and Nov 2004. The eligible pts were 299 (Arm A/B, 150/149). Median age was 62.0/61.5 yrs. At a 2 yrs follow-up since last patient in, the MST for Arm A was 335.5 days (95%CI: 292.0 - 402.0) and for Arm B was 396.0 days (95%CI: 342.0 - 471.0). The OS for Arm B was superior to Arm A (log-rank p=0.0366, hazard ratio: 0.774, 95% CI: 0.608 - 0.985). RR was 31.1% for Arm A and 54.0% for Arm B. In Arm A vs Arm B, the most common grade 3/4 toxicities were: leucopenia, 2.0% vs 11.5%; neutropenia, 10.7% vs 39.9%; anemia (decreased Hb), 4.0% vs 25.7%; nausea, 1.3% vs 11.5%; anorexia, 6.0% vs 30.4%. No treatment related death was observed. Conclusions: The combination treatment of S-1 and CDDP met primary endpoint of OS, and was found to be effective and well tolerated in pts with AGC. Accordingly, this regimen can be regarded as one of first-line standard treatment for AGC. No significant financial relationships to disclose.

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