The use of trastuzumab in Japanese patients with HER2-positive advanced or metastatic gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 102-102
Author(s):  
A. Sawaki ◽  
Y. Ohashi ◽  
Y. Omuro ◽  
T. Satoh ◽  
Y. Hamamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Japanese Population ◽  
Cox Regression ◽  
Controlled Trial ◽  
Japanese Patients ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Positive ◽  
Baseline Characteristics

102 Background: The Trastuzumab for Gastric Cancer (ToGA) study showed the efficacy of trastuzumab for HER2-positive gastric cancer (HGA). The aim of this study is to evaluate the benefit of trastuzumab for Japanese HGA patients. Methods: ToGA was an open-label, international, phase III, randomized controlled trial undertaken in 122 centers in 24 countries. Median overall survival (OS) was 13.8 months in those assigned to trastuzumab plus chemotherapy (C+T) compared with 11.1 months in those assigned to chemotherapy alone (C) with hazard (HR) ratio of 0.74. Subgroup analyses of patients enrolled from Japan were undertaken to estimate the hazard ratio (HR) for OS in the Japanese population. Based upon the prescribed protocol for Japan, we calculated HR using multiple Cox regression model with prespecified covariates in the ToGA study in order to make up for the small number of Japanese patients and reduce the bias in the baseline characteristics between two groups. Results: Sixteen institutes participated and 102 patients were enrolled, of which 101 patients were evaluable for this research. The median OS was 15.9 months in C+T arm versus 17.7 months in C arm. The HR for OS was 1.00 [95% CI: 0.59-1.69]. However, the HR for OS adjusted for the above covariates was estimated to be 0.68 [95% CI: 0.36-1.27]. There were differences between C+T arm and C arm in some baseline characteristics. Higher frequencies were seen in C arm as follow: intestinal type, prior gastrectomy, and smaller number of metastatic sites. For HER2 status, the percentage of patients with IHC0/FISH+ was lower in C+T arm (5.9%) than in C arm (18.0%), while that of patients with HER2 status IHC2+/FISH+ was higher in C+T arm (35.3%) than in C arm (26.0%). Conclusions: Although ToGA's overall OS HR = 0.74 (p = 0.0046), in the Japan patient subgroup, the unadjusted hazard ratio was 1.00. However, there was an imbalance of the baseline characteristics between the treatment arms in Japanese population. When adjusted for these characteristics, the HR was 0.68 which is similar to those in the ToGA study. Adding trastuzumab to chemotherapy in Japanese population appears to confer a similar magnitude of benefit compared to the whole population enrolled in the ToGA study. [Table: see text]

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.

Result of HER2 status in Japanese metastatic gastric cancer: Prospective cohort study (JFMC44-1101).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 10-10 ◽  
Author(s):  
Kazuhiro Nishikawa ◽  
Keisho Chin ◽  
Atsushi Nashimoto ◽  
Akira Miki ◽  
Hiroto Miwa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Positive ◽  
Ffpe Tissues ◽  
Her2 Positivity

10 Background: Randomized phase III (ToGA trial) has demonstrated that the addition of trastuzumab to standard chemotherapy improved overall survival in patients (pts) with HER2-positive metastatic gastric cancer (mGC). In screening of the ToGA trial, HER2 positivity rate was 22.1 % in total, but the rates varies between countries. Therefore, to determine the HER2 incidence rate in Japanese mGC, we planned prospective cohort study JFMC44-1101. Methods: JFMC44-1101 is a multicenter epidemiological trial assessing HER2 status in Japan. Patients with histologically confirmed gastric adenocarcinoma, not suitable for curative resection were eligible. HER2 status was centrally assessed both immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) using formalin fixed paraffin embedded (FFPE) tissues from tumor. HER2 positive is defined as either IHC3+ or FISH+ in accordance with ToGA trial. Overall and subgroup estimates calculated with 95%CI. Results: Between September 2011 to June 2012, 1466 pts were registered from 157 sites. Patients characteristics were; gender (M/F):1044/422, median age (min-max): 68 (25-99), advance / recurrence: 1068 / 398. Samples are 768 from biopsy and 698 from excision. In August 2012, 1427/1466 pts were assessed. Overall, HER2 positivity was 20.5% (293 pts). Each IHC status (0/1+/2+/3+) with FISH+ was 3.0% / 11.3% / 46.9% / 97.2%, respectively. The frequency of IHC 0/1+ with FISH+ was almost as high as IHC 2+ with FISH+ (5.6%/4.2%). HER2 positivity rate of background factors were; male/female:23.6%/14.3%, biopsy/ excision: 22.7%/19.0%, advance / recurrence: 21.6%/17.6%. Conclusions: JFMC44-1101 confirmed the incidence of HER2 positivity in Japanese mGC. HER2-positivity rate and HER2 status were similar to the ToGA screening population. Clinical trial information: UMIN000006190.

Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2 positive resectable esophagogastric adenocarcinoma: Petrarca—A phase II trial of the German AIO.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4133-TPS4133 ◽  
Author(s):  
Ralf Hofheinz ◽  
Gerrit zur Hausen ◽  
Kersten Borchert ◽  
Albrecht Kretzschmar ◽  
Matthias Philip Ebert ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Phase Iii ◽  
Her2 Status ◽  
Her2 Positive ◽  
Pathological Complete Remission

TPS4133 Background: Neoadjuvant or perioperative chemotherapy has become a standard of care for locally advanced, resectable gastric cancer and adenocarcinoma of the GEJ. However, patient’s outcome is still unsatisfactory and 5-year survival, even in prospective trials, has been below 40%. Targeting HER2 with Trastuzumab and Pertuzumab prolonged survival in patients with HER2-positive advanced breast cancer as did Trastuzumab in patients with HER2-positive advanced gastric cancer. This provides a rationale for the evaluation of anti-HER2 treatment for resectable patients. Methods: This is a prospective, multicenter, randomized, investigator initiated phase II trial. Patients with HER2-positive locally advanced adenocarcinoma of the stomach and GEJ (i.e. ≥cT2 any N or any T N-positive) with exclusion of distant metastases are enrolled. HER2 status is centrally assessed. Patients are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m²) followed by surgery and 4 additional cycles of FLOT (arm A); or the same therapy in combination with Trastuzumab 8/6 mg/kg and Pertuzumab 840 mg every 3 weeks pre- and postop, followed by a total of 9 additional cycles of Trastuzumab/Pertuzumab monotherapy (arm B). Primary endpoint of the phase II part (n = 100) of the trial is to show numerical improvement of the rate of pathological complete remission to approx. 25% with antibodies compared to approx. 16% with FLOT alone as assessed by a centralized pathology. Main secondary endpoints are safety and tolerability. Once results from phase II become available, study transition into phase III will be evaluated based on de facto results and current medical standards. Recruitment has already started; by February 2017 a total of 19 patients have been randomized. EudraCT: 2014-002695-86 Clinical trial information: NCT02581462.

Assessment of HER2 status from an epidemiology study in tumor tissue samples of gastric and gastro-esophageal junction cancer: Results from the french cohort of the HER-EAGLE study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 26-26
Author(s):  
Genevieve Monges ◽  
Benoit Terris ◽  
Marie-Pierre Chenard ◽  
Frederique Penault-Llorca ◽  
Sophie Beauclair ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Iii ◽  
Her2 Status ◽  
Routine Practice ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Tissue Samples ◽  
French Cohort ◽  
Her2 Positivity ◽  
Eagle Study

26 Background: HER2 is an important prognostic and also a predictive biomarker for trastuzumab response in gastric cancer. Therefore, HER2 status should be tested in all gastro-esophageal junction (GEJ) and gastric cancer (GC) patients. ToGA phase III study showed a benefit in overall survival of trastuzumab added to standard chemotherapy in patients with HER2-positive advanced GEJ/GC. The objective of the HER-EAGLE study was to assess the incidence of HER2 positivity in GEJ/GC cancer. Methods: HER-EAGLE was an international epidemiological, non-interventional study assessing HER2 status by IHC/ISH in tumor samples from any stage in patients with GEJ/GC. Samples were obtained by excision or core biopsy and routinely analyzed via validated Ventana or Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+ or IHC 2+ if FISH/SISH negative ratio < 2.0. Overall and subgroup estimates calculated with 95% CI. Data from the French cohort are presented. Results: The HER-EAGLE French cohort included 267 patients (68.6% males) from 7 centers (May 2007 to March 2012), with 150 biopsies (56.2%) and 117 excisions (43.8%). Tumor locations were 65.9% stomach and 34.1% GEJ, and adenocarcinoma types were according to Lauren classification: 170 intestinal (63.7%), 72 diffused (27%), 22 mixed (8.2%) and 3 not available (1.1%). HER2 status was: 36 cases IHC 3+ (13.5%), 51 IHC 2+ (19.1%) whereof 18 ISH positive (35.3%), 35 IHC 1+ (13.1%) and 145 IHC 0 (54.3%). Overall HER2 positivity (IHC 3+ or IHC 2+/ISH+) was 20.2%. Heterogeneity for HER2 staining was observed in 81 samples (30.3%). No statistical difference was found according to cancer stage. HER2 positivity was higher in GEJ (31.9%) than in GC (14.2%), p<0,001, and higher in intestinal (28.2%) compared to diffused adenocarcinomas (5.6%), p<0,001. Conclusions: HER-EAGLE French cohort results confirmed the feasibility of HER2 testing in GEJ/GC in routine practice. The incidence of HER2 overexpression was similar to the literature review, and it was higher in GEJ and intestinal adenocarcinomas type.

scholarly journals Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Hiromi Nagata ◽  
Hironori Tsujimoto ◽  
Yoshihisa Yaguchi ◽  
Keita Kouzu ◽  
Yujiro Itazaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rare Case ◽  
Metastatic Tumor ◽  
Endoscopic Biopsy ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Standard Regimen ◽  
Mixed Adenoneuroendocrine Carcinoma ◽  
Her2 Positivity

Abstract Background Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer. Case presentation A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor. Conclusions We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.

scholarly journals Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Ishimine ◽  
Akira Goto ◽  
Yoshito Watanabe ◽  
Hidetaka Yajima ◽  
Suguru Nakagaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Residual Tumor ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Curative Intent ◽  
Course Of Disease ◽  
Trastuzumab Therapy ◽  
Her2 Positivity

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 128-128
Author(s):  
Kohei Shitara ◽  
Yasushi Yatabe ◽  
Masato Sugano ◽  
Keitaro Matsuo ◽  
Chihiro Kondo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Small Sample Size ◽  
Small Sample ◽  
Her2 Status ◽  
First Line ◽  
Her2 Positive ◽  
Line Therapy ◽  
The Impact ◽  
Time Varying Covariates ◽  
Line Chemotherapy

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.

Significance of accurate HER2 testing as a new biomarker in advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 106-106
Author(s):  
Tetsuya Kusumoto ◽  
Hajime Ohtsu ◽  
Hiroyuki Kawano ◽  
Koji Ando ◽  
Satoshi Ida ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Tumor Biology ◽  
Japanese Patients ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Gastroesophageal Junction Cancer ◽  
Her2 Heterogeneity

106 Background: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2)-positive advanced or recurrent gastric or gastroesophageal junction cancer, which demonstrated that trastuzumab plus chemotherapy improved overall survival in the overall population (hazard ratio 0.74). HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in Japanese patients with advanced gastric cancer (AGC) and to investigate the relationships between HER2 expression and therapeutic responses. Methods: A total of 199 tumor samples were assessed for HER2 expression both by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH). HER2-positive status was defined as IHC2+ and FISH-positive or IHC3+. Objective responses were evaluated in the patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2 expression status. Results: HER2-positive tumors were identified in 12 patients (5.5%), less than 28.1% in the Japanese subgroup analyses of ToGA study. The positive rates varied with histological type; 14%, 5.3% and 0.95% in the well, moderately and poorly differentiated adenocarcinoma, respectively. Although high concordance between the results of IHC and FISH in all samples was found, IHC2+ samples retested here showed FISH-negative. Of all 10 patients with AGC, 3 patients with HER2-positive tumor were treated with capecitabine/cisplatin plus trastuzumab, and partial response was found in 2 cases; response rates were 67%. Conclusions: Specific consideration and scoring modification are required before embarking on HER2 testing in gastric cancer. Accurate and reliable HER2 testing and scoring will allow appropriate selection of patients eligible for treatment with trastuzumab.

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