Updated analysis of HERBIS-1: A phase ll study of trastuzumab (T-mab) in combination with tri-weekly S-1 plus CDDP in HER2-positive advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 98-98
Author(s):  
Makio Gamoh ◽  
Naotoshi Sugimoto ◽  
Hiroto Miwa ◽  
Masahiro Tsuda ◽  
Shinichi Nishina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Event Analysis ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Esophagogastric Junction Adenocarcinoma

98 Background: The HERBIS study demonstrated the promising antitumor activity and manageable toxicities of S-1 plus cisplatin and T-mab (SPT) regimen in patients (pts) with HER2-positive advanced gastric cancer (AGC) (Sugimoto et al. ASCO GI 2012, Abstract 70). We report the updated time-to event analysis. Methods: Main eligibility criteria were gastric or esophagogastric junction adenocarcinoma, HER2-positive, unresectable or recurrent, measurable lesion, no history of chemotherapy or radiotherapy, ECOG PS of 0-1 and adequate organ function. Pts received S-1(80-120mg / day) on days 1-14, cisplatin 60 mg/m2on day 1 and T-mab 8 mg/ kg on day 1 (6 mg/ kg from 2nd course) repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR) and secondary endpoints were overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and adverse events. The planned sample size was 50 pts. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible and one patient did not receive any treatment. Therefore, the efficacy and safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate was 67.9% (95% CI: 53.7-80.1), and the disease control rate was 94.3% (95% CI: 84.3-98.9). Median OS was 16.0 months (95% CI: 13.3 - NaN), median PFS was 7.8 months (95% CI: 6.0 – 8.8) and median TTF was 5.7 months (95% CI: 4.2 - 7.1), respectively at the median follow-up time of 13.5 months. The main grade 3/4 adverse events were leukopenia 8%, neutropenia 36%, anemia 15%, increased creatinine 6%, hypoalbuminemia 9%, anorexia 23%, diarrhea 8% and vomiting 6%. Conclusions: SPT have promising antitumor activity and manageable toxicities in pts with HER2-positive AGC. Clinical trial information: UMIN000005739.

A phase ll study of trastuzumab in combination with triweekly S-1 plus CDDP in HER2-positive advanced gastric cancer (HERBIS-1).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 70-70 ◽  
Author(s):  
Naotoshi Sugimoto ◽  
Junji Tanaka ◽  
Masahiro Tsuda ◽  
Wataru Okamoto ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Rapid Progression ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Threshold Response ◽  
Esophagogastric Junction Adenocarcinoma ◽  
Ecog Ps ◽  
Measurable Lesion

70 Background: S-1, an oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer (AGC). Although ToGA study demonstrated that trastuzumab (T-mab) in combination with capecitabine plus cisplatin or fluorouracil plus cisplatin improved the overall survival of patients (pts) with HER2-positive AGC, there was no study evaluating the efficacy and the safety of T-mab in combination with SP regimen. Methods: Eligibility criteria included gastric or esophagogastric junction adenocarcinoma; HER2-positive confirmed by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive); unresectable or recurrent; measurable lesion; no history of chemotherapy or radiotherapy; age≤75; ECOG PS of 0-1; and adequate organ function. Pts received S-1 at 40–60 mg depending on body surface area, po bid, day 1-14, and cisplatin 60 mg/m2, iv, day 1, plus T-mab 8 mg/ kg, iv, day 1 (6 mg/ kg, iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate assessed by the RECIST (ver 1.1). The planned sample size was 50 based on the threshold response rate of 35%, the expected rate of 50%, power of 80%, and 1-sided α of 0.1. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible with inadequate renal function and no measurable lesion. Characteristics of 54 eligible pts were as follows: median age of 66 (range 34-75), M/F: 42/12, PS0/1: 42/12, unresectable/recuurent: 51/3, and IHC 2+/3+: 9/45. As one patient did not receive the protocol treatment due to the rapid progression of tumor, the efficacy and the safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate assessed by the independent review committee was 68%, and the disease control rate was 94%. The response rate without interval confirmation was 75%. The grade 3/4 adverse events (>5% of pts) were as follows: neutropenia 30%, leucopenia 8%, anorexia 21%, diarrhea 8%, hypoalbuminemia 8%, vomiting 6%, and increased creatinine 6%. Conclusions: T-mab in combination with triweekly SP regimen showed promising antitumor activity and manageable toxicities in pts with HER2-positiveAGC. Clinical trial information: UMIN000005739.

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

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 119-119 ◽  
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.

A phase ll study of new combination regimen with trastuzumab, S-1, and CDDP in HER2-positive advanced gastric cancer (HERBIS-1).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4072-4072
Author(s):  
Keisuke Koeda ◽  
Naotoshi Sugimoto ◽  
Junji Tanaka ◽  
Masahiro Tsuda ◽  
Wataru Okamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
New Combination ◽  
Combination Regimen ◽  
Her2 Positive ◽  
Threshold Response ◽  
Grade 3

4072 Background: S-1, a novel oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. ToGA study demonstrated that trastuzumab (T-mab) combination regimen improved the overall survival of patients with HER2-positive advanced gastric cancer. However, there was no study evaluating the efficacy and the safety of T-mab in combination with S-1 plus cisplatin (SP) regimen. Therefore, we planned this study to examine the efficacy and the safety of the SP plus T-mab. Methods: Patients confirmed to be HER2-positive by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive) received S-1 at 80 mg/m2 po, day 1-14, and cisplatin 60 mg/m2 iv, day 1 plus trastuzumab 8 mg/kg iv, day 1 (6 mg/kg iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR). Secondary endpoints were progression-free survival, overall survival and safety. The threshold response rate was defined as 35%, and the expected rate was set at 50% with a 80% power and a 1-sided alpha value of 0.1 and the calculated sample size was 50 patients. Results: A total of 56 patients (median age 66) were enrolled in this study. The efficacy and the safety analyses were conducted in the full analysis set of 53 patients. (Two patients were excluded for ineligibility and one was for no treatment). The confirmed RR assessed by the independent review committee was 67.9% (95% CI: 53.7 – 80.1), and the disease control rate was 94.3%. The median PFS was 7.1 months (95% CI: 6.0 – 10.1). The median OS was not reached. (The median follow-up time: 9.2 months) The main grade 3/4 adverse events were as follows: neutropenia 34%, leucopenia 8%, anorexia 23%, diarrhea 8%, hypoalbuminemia 4%, vomiting 6%, and increased creatinine 6%. Conclusions: This tri-week regimen with SP plus T-mab showed promising results in patients with HER2-positive advanced gastric cancer. Clinical trial information: UMIN000005739.

A phase Ib study of nivolumab plus trastuzumab with S-1/capecitabine plus oxaliplatin for HER2 positive advanced gastric cancer (Ni-HIGH study).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS177-TPS177 ◽  
Author(s):  
Daisuke Takahari ◽  
Takeru Wakatsuki ◽  
Naoki Ishizuka ◽  
Naoki Fukuda ◽  
Hirokazu Shoji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Tumor Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Phase Ib ◽  
Her2 Breast Cancer ◽  
Biomarker Analysis

TPS177 Background: Trastuzumab (Tmab) with cisplatin and fluoropyrimidines improved the overall survival (OS) of patients (pts) with HER2 (+) advanced gastric cancer (AGC). Nivolumab (Nivo) is an anti-programmed cell death-1 (PD-1) antibody that demonstrated a survival benefit as third line or later of AGC. To date, most trials investigating anti-PD-1 antibody for 1st line treatment focus on HER2 (-) AGC. In HER2(+) breast cancer mouse model, combining Tmab with anti-PD-1 antibody was reported to enhance ADCC activity of Tmab, and show greater tumor regression. In our data, the PD-L1 expression was observed in 44% of tumor cells and 70% of immune cells in human HER2(+) AGC. Based on these data, we have plannedthis phase Ib investigator-initiated trial to investigate the safety and tolerabirity of Nivo plus Tmab and either S-1 or capecitabine (Cape) plus Oxaliplatin (Ox) for pts with HER2(+) AGC. Methods: Histopathologically confirmed HER2(+) AGC with mesurable lesions, aged > 20 years, chemo-naïve pts are enrolled in this study. Pts receive Nivo (360 mg/body; day 1) plus Tmab (course1, 8 mg/kg; course 2 onward, 6 mg/kg; day 1) and either S-1 (40 mg/m2 bid d1-14; cohort 1) or Cape (1000 mg/m2 bid d1-14; cohort 2) plus Ox (130 mg/m2; day 1) every three weeks until desease progression or unacceptable toxicity. In the primary part, six pts for each cohort will be assessed for tolerability.To estimate the objective response rate (ORR) in the analysis-set, on our hypothesis that a true response rate is 80%, 20 pts are required for the 90% C.I. to be ± 20%. Therefore the expansion part for each cohort will be 12-15 pts. Primary endpoint is safety. Secondary endpoint is tolerability and exploratory endpoints include ORR, disease control rate, progression free survival and OS. Collaborative biomarker analysis includes whole exome sequences, RNA sequences, gut microbiome, and IHC using biopsy specimens. In addition, T-cell repartry, circulating tumor DNA and exomes will be also analyzed using blood obtained during treatment. This study just has been initiated at four sites in Japan. Clinical trial information: UMIN000034222.

Multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Toshiki Masuishi ◽  
Tomono Kawase ◽  
Kazuhiro Nishikawa ◽  
Chikara Kunisaki ◽  
Satoshi Matsusaka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Adverse Events ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Statistical Power ◽  
Her2 Positive ◽  
Standard Regimen ◽  
End Point ◽  
Her 2

106 Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. In patients with HER2-positive AGC, ToGA trial showed survival benefit with the addition of trastuzumab to capecitabine plus cisplatin or fluorouracil plus cisplatin and HERBIS-1 trial demonstrated promising antitumor activity with the addition of trastuzumab to SP. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. And these disadvantages of cisplatin are noticeable in elderly patients. We evaluated the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. Methods: Patients, 65 years or older, with HER2-positive AGC received S-1 (80–120mg per day) orally on days 1–28 of a 42-day cycle and trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg /kg) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary endpoints were overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and adverse events. The sample size was 40 to 60 patients estimated on the basis of threshold RR=20%, expected RR=35%, alpha=0.1 (one-sided) and power=80 to 90%. Results: A total of 51 patients were enrolled. One patient was ineligible, therefore in the full analysis set of 50 patients (actual statistical power = 87.5%), the median age was 71 years (range=65-85), male: female was 37:13 and ECOG PS was 0/1/2= 33/14/3. The confirmed RR (CR/PR/SD/PD=3/17/23/7) was 40.0% (80% confidence interval (CI); 31.1-48.9%, 95% CI; 26.4-53.6%), and the null hypothesis was rejected. The disease control rate was 86.0% (95% CI; 76.4-95.6%). Median OS, PFS, and TTF were immature. Major grade 3 or 4 adverse events included neutropenia (10.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: The primary end point was met. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects in elderly patients with HER2-positive AGC. Clinical trial information: UMIN000007368.

A phase II study (KSCC/HGCSG/CCOG/PerSeUS1501B) of trastuzumab plus S-1 and oxaliplatin for HER2-positive advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4059-4059 ◽  
Author(s):  
Katsunori Shinozaki ◽  
Satoshi Yuki ◽  
Tomomi Kashiwada ◽  
Tetsuya Kusumoto ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Incidence Rates ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Standard Regimen

4059 Background: A combination of S-1 and cisplatin (SP) has been the standard regimen for advanced gastric cancer (AGC) in East Asia. The combination of S-1 and oxaliplatin (SOX100) was demonstrated to be non-inferior to SP in the randomized phase III study. The ToGA study demonstrated that trastuzumab (T-mab) combination therapies with cisplatin and fluoropyrimidines improved the overall survival of patients with HER2-positive AGC. This multicenter study is the first phase II trial to assess the efficacy and safety of T-mab in combination with S-1 and oxaliplatin (HER-SOX130) in HER2-positive AGC. Methods: Patients with HER2-positive AGC or recurrent gastric cancer defined to be IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 S-1 per day orally on days 1–14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). Adverse events were recorded based on the NCI-CTCAE Vers.4.0. The threshold response rate was defined as 50%, and the expected rate was set at 70%, with an 80% power and a 1-sided alpha value of 0.05. The calculated sample size was 37 patients. Results: For this study, 42 patients (median age, 66 years) were enrolled from June 2015 to May 2016. Three patients were excluded owing to ineligibility. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The proportion of patients with IHC 3+ was 87%. The confirmed RR assessed by the independent review committee was 82.1(32/39) % (95% confidence interval [CI]: 67.3–91.0), and the disease control rate was 87.2(34/39) % (95% CI: 73.3–94.4). The incidence rates of grade 3 or 4 adverse events were as follows: neutropenia, 12.8%; thrombocytopenia, 17.9%; anemia, 10.3%; sensory neuropathy, 5.1%; anorexia, 17.9%; diarrhea, 7.7%; and teary eyes, 2.6%. Conclusions: HER-SOX130 demonstrated encouraging efficacy with a favorable safety profile. The survival benefit of this regimen needs to be validated by conducting further follow-up of patients. Clinical trial information: 000017552.

A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15050-15050
Author(s):  
S. Yoshino ◽  
T. Nishimura ◽  
S. Hazama ◽  
M. Oka ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Outpatient Setting ◽  
Eligibility Criteria ◽  
Line Therapy ◽  
Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

Efficacy of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination (NVBoXH) in HER2-positive metastatic breast cancer (MBC): First results of an international phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1052-1052 ◽  
Author(s):  
A. Chan ◽  
V. Ganju ◽  
D. Becquart ◽  
P. Conte ◽  
L. Petruzelka ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
First Line ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Oral Vinorelbine

1052 Background: Chemotherapy (CT) plus H is the standard first-line treatment for HER2-positive MBC. H plus vinorelbine is an active and well-tolerated regimen in this setting. The all-oral combination of NVBo and X also appears active and well-tolerated in MBC. We report efficacy and safety results from the first 34 patients (pts) included in an international trial evaluating NVBoXH in HER2-positive MBC. Methods: In this multicenter trial, main eligibility criteria included: HER2-positive disease (IHC 3+ or FISH+), documented measurable MBC previously untreated by CT, relapse 6 months after completing neoadjuvant or adjuvant CT, Karnofsky PS = 70, age =18 years. Pts received 3-weekly cycles of NVBo 60 mg/m2 (cycle 1) escalating to 80 mg/m2 (from cycle 2) days 1 and 8; × 1,000 mg/m2 bid (750 if = 65 years) days 1–14; H 4 mg/kg day 1 as a loading dose then 2 mg/kg i.v. weekly starting on day 8. Treatment was continued until progression or unacceptable toxicity. Primary endpoint is overall response rate. Results: Baseline characteristics: median age 54 years (20% = 65); prior (neo)adjuvant CT 21 pts (62%); type of CT: anthracycline 52%, anthracycline + taxane 29%, CMF 14%, taxane 5%; visceral involvement 29 pts (85%), >2 metastatic sites 13 pts (38%). Treatment administered: median 8 cycles, median relative dose intensity: NVBo 77%, X 81%, H 95%; NVBo dose escalation to 80 mg/m2 in 91% of pts. Safety (n=34, G3/4 NCI CTC v2 adverse events): neutropenia 22 pts (65%), diarrhea 4 pts (12%), febrile neutropenia 3 pts (9%), vomiting 3 pts (9%), hand-foot syndrome 3 pts (9%), asthenia 3 pts (9%), infection without neutropenia 2 pts (6%), LVEF decline 2 pts (6%), stomatitis 1 pt (3%), nausea 1 pt (3%), constipation 1 pt (3%). Efficacy (n=31 evaluable pts): objective response rate (RECIST) 71% (95% CI [52–86]), CR 13%, PR 58%, SD 23%, PD 6%, disease control (CR+PR+ SD for =6 months) 84%. Progression-free survival, overall survival and duration of response data are not yet mature. Conclusions: This is the first trial, in pts with HER2-positive MBC, to show high efficacy with first-line NVBoXH therapy. This regimen can be safely administered in this pt population. No significant financial relationships to disclose.

A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Daisuke Sakai ◽  
Junji Kawada ◽  
Ryohei Kawabata ◽  
Tomono Kawase ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Disease Control ◽  
Intravenous Infusion ◽  
Response Rate ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Free Survival

128 Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m2; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.

Second-line chemotherapy with paclitaxel for elderly patients with advanced gastric cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Akihiro Ohba ◽  
Atsuo Takashima ◽  
Takamasa Nishiuchi ◽  
Yoshitaka Honma ◽  
Satoru Iwasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Progression Free Survival ◽  
The Elderly ◽  
Elderly Group ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

108 Background: Survival benefits of second-line chemotherapy such as weekly paclitaxel (wPTX) for patients with advanced gastric cancer (AGC) were shown in several phase 3 trials. However, these trials included a small proportion of elderly patients, and few elderly patients receive second-line therapy in clinical practice. The aim of this study was to compare the efficacy and safety of second-line chemotherapy with wPTX between elderly and non-elderly patients. Methods: The subjects of this retrospective study were AGC patients who received wPTX as second-line chemotherapy between January 2002 and August 2014, fulfilling the following selection criteria; 1) pathologically proven metastatic or recurrent gastric adenocarcinoma, 2) receipt of wPTX after platinum or fluoropyrimidine containing chemotherapy. Patients were divided into two groups by age: ≥ 75 years old (elderly group) and < 75 years old (non-elderly group). Response rate (RR) in patients with measurable lesions, overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) and adverse events were evaluated. Hazard ratios of survival were adjusted by prognostic factors using Cox proportional hazard model. Results: A total of 272 patients, 31 elderly and 241 non-elderly, were selected in this study. RRs were 6.2% (1/16) in the elderly group and 12.7% (15/118) in the non-elderly group (p = 0.69). While PFS was similar between two groups (median 2.4 vs. 3.6 months, adjusted hazard ratio [HR] 1.18, p = 0.46), the elderly group showed shorter OS than the non-elderly group (median 5.1 vs. 6.1 months, adjusted HR 1.49, p = 0.06), associated with relatively shorter PPS (median 2.2 vs. 2.6 months, adjusted HR 1.40, p = 0.11). There were no remarkable differences in the incidences of grade 3 or higher adverse events between the two groups (hematologic 38.7 vs. 41.1%; non-hematologic 25.8 vs. 23.7%). No treatment related deaths were observed in either group. Third-line chemotherapy was administered in 19.4% of elderly group and 35.3% of non-elderly group (p = 0.11). Conclusions: It is suggested that second-line chemotherapy with wPTX for AGC may be tolerable and have some clinical benefits for elderly patients as well as for non-elderly patients.

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