Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604)

2018 ◽  
Vol 105 ◽  
pp. 41-49 ◽  
Author(s):  
Hiroshi Saeki ◽  
Eiji Oki ◽  
Tomomi Kashiwada ◽  
Takaaki Arigami ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Her2 Status ◽  
Her2 Positive ◽  
Recurrent Gastric Cancer

Multicenter observational study on re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 4038-4038 ◽  
Author(s):  
Tomomi Kashiwada ◽  
Hiroshi Saeki ◽  
Yoshikazu Uenosono ◽  
Akitaka Makiyama ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Observational Study ◽  
Her2 Status ◽  
Her2 Positive ◽  
Multicenter Observational Study ◽  
Recurrent Gastric Cancer

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.

Prognostic factors for survival in patients with advanced gastric cancer treated with chemotherapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 142-142
Author(s):  
Montserrat Mangas ◽  
Alberto Carmona Bayonas ◽  
Maria Luisa Sanchez Lorenzo ◽  
Avinash Ramchandani ◽  
Teresa Garcia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Group Performance ◽  
Gastroesophageal Junction ◽  
Cox Proportional Hazards Model ◽  
Her2 Status ◽  
Her2 Positive ◽  
Ecog Ps

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]

A phase Ib, first-in-human, dose escalation and expansion study of XMT-1522, a novel antibody-drug conjugate (ADC) directed against HER2, in patients with advanced breast cancer and other advanced tumors expressing HER2.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2606-TPS2606 ◽  
Author(s):  
Howard A. Burris ◽  
Minal A. Barve ◽  
Erika Paige Hamilton ◽  
Aditya Bardia ◽  
Hatem Hussein Soliman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Advanced Breast Cancer ◽  
Dose Escalation ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Her2 Status ◽  
Her2 Positive ◽  
Post Dose ◽  
Human Dose

TPS2606 Background: XMT-1522 is an ADC consisting of a novel human IgG1 anti-HER2 monoclonal antibody conjugated to an auristatin-based cytotoxic payload (AF-HPA). An average of 12 AF-HPA molecules is conjugated to each antibody via a biodegradable polymer. In pre-clinical xenograft experiments XMT-1522 achieved complete, durable tumor regressions in models of HER2-positive and HER2 1+/2+ breast cancer, HER2 2+/3+ NSCLC, and HER2-positive and HER2 1+ gastric cancer. Methods: This study (NCT02952729) is comprised of two parts: a dose escalation segment (DES) and an expansion segment (EXP). The primary objectives of the DES are determination of the maximum tolerated dose and recommended Phase 2 dose (RP2D) and assessment of safety and tolerability. The DES will enroll patients with advanced or metastatic breast cancer who have progressed following standard therapies and have HER2 protein at least 1+ by IHC. XMT-1522 will be administered intravenously every 3 weeks. DES uses a 3+3 design. Post-dose assessments include LVEF measurement at the end of cycles 1, 3, then every 3 cycles, ophthalmologic exams at the end of cycles 1, 2, then every 2 cycles, and re-staging CT scans every 2 cycles. Pharmacokinetics of antibody, AF-HPA payload and an AF-HPA metabolite will be measured. Two patients have completed dose level 1 without DLT. The EXP segment will open at the RP2D and will further assess safety and tolerability of XMT-1522 and assess efficacy in selected patient populations. EXP will enroll 4 cohorts (N = 20 each). Cohort 1: HER2 1+/2+ advanced breast cancer with 2-3 prior chemotherapy regimens Cohort 2: HER2-positive advanced breast cancer with prior pertuzumab and ado-trastuzumab emtansine (T-DM1) Cohort 3: HER2-positive advanced gastric cancer with prior trastuzumab Cohort 4: HER2 2+/3+ NSCLC with at least 1 prior platinum regimen The protocol requires archival tumor tissue for central confirmation of HER2 status, alternative HER2 measurements, and targeted gene expression and sequencing studies. Tumor biopsies will be requested at the time of progression from patients who responded to XMT-1522. Clinical trial information: NCT02952729.

Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: Results of GASTric cancer HER2 reassessment study 3 (GASTHER3).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 27-27 ◽  
Author(s):  
Seyoung Seo ◽  
Min-Hee Ryu ◽  
Ji Yong Ahn ◽  
Yangsoon Park ◽  
Sook Ryun Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Genetic Heterogeneity ◽  
Objective Response ◽  
Progression Free Survival ◽  
The Other ◽  
Wilcoxon Test ◽  
Her2 Status ◽  
Her2 Positive ◽  
Her2 Positivity ◽  
Negative Conversion

27 Background: Although discordance of HER2 positivity between primary and metastatic lesions was well known, changes of HER2 positivity after chemotherapy have not been studied in gastric cancer (GC). Methods: A total of 48 HER2-positive advanced GC (AGC) patients who were treated with trastuzumab-containing 1stline chemotherapy and had paired biopsies at baseline and after progression were enrolled. Scores of HER2 immunohistochemistry (IHC) were reviewed and in situ hybridization (ISH) was conducted when tissues were available. Results: Thirty-nine patients were treated with capecitabine, cisplatin/oxaliplatin, and trastuzumab (XPT) while the other 9 received XPT plus pertuzumab/placebo. Objective response rate (ORR) was 76% (26 out of 34) and median progression free survival (PFS) and overall survival were 8.3 and 16.3 months, respectively. At baseline, HER2 was positive with IHC 2+ and ISH+ in 5 and with IHC 3+ in 43. Loss of HER2 positivity after progression was observed in 14 (28.6%); 10 with IHC 0 or 1+ and 4 with IHC 2+ but ISH- at 2nd biopsy. HER2 remained positive in the other 34; 4 with IHC2+ and ISH+, and 30 with IHC 3+ at 2nd biopsy. Applying H-score formula, mean scores decreased from 201 to 170 (Wilcoxon test; p=0.047). HER2 genetic heterogeneity (5% to <50% of tumor nuclei showing a HER2:CEP17 ratio ≥2) was noted only 1 out of 34 ISH-assessable patients (2.9%) at baseline while 7 out of 32 ISH-assessable patients (21.9%) had heterogeneity at 2nd biopsy. The mean ratio was changed from 6.5 (1.2-15.8) to 5.0 (0.4-15.2) (paired t-test, p=0.019) and all patients with genetic heterogeneity at 2ndbiopsy showed HER2 negative conversion. Among 13 who received 2ndline T-DM1, 3 showed HER2 negative conversion. Those 3 had no objective response at all and very short PFS (1.2, 1.3 and 3.4 months), whereas the others with stable HER2 status showed 44% of ORR and median PFS of 2.7 (0.4-36.8) months. Conclusions: A substantial portion of initially HER2-positive AGC patients showed HER2 negative conversion with increased HER2 heterogeneity after trastuzumab-containing chemotherapy. Loss of HER2 positivity could be a predicting factor for 2nd line anti-HER2 treatment.

Profiling of circulating tumor cells isolated from 105 metastatic gastric cancer patients revealed HER2 overexpression/activation for potential use in clinical setting.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10535-10535 ◽  
Author(s):  
Saswati Hazra ◽  
Jeeyun Lee ◽  
Phillip Sangwook Kim ◽  
Kyoung-Mee Kim ◽  
Limin Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Predictive Marker ◽  
Patient Treatment ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Over Expression

10535 Background: Gastric cancer (GCA) is the second leading cause of cancer mortality in the world. Survival of patients with advanced GCA treated with chemotherapy remains low. New targeted therapies are urgently needed. There is mounting evidence of the role of HER2 overexpression in patients with GCA, and it has been highly correlated to poor outcomes with more aggressive disease. The ability to accurately determine HER2 status by testing circulating tumor cells (CTCs) may improve patient treatment by allowing ongoing assessment of HER2 status during treatment and/or identifying additional patients who could potentially benefit from HER2- targeted therapy. Methods: The Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) was utilized to determine the expression and activation (phosphorylation) levels of HER2 in CTCs isolated from blood specimens obtained from 105 metastatic GCA patients. Results: Utilizing the CEER platform, the levels of HER2 expression and phosphorylation were determined for CTCs isolated from metastatic GCA patients. Evaluable CTCs were found in 33% (35/105) of enrolled patients. Out of 35 patients, 7 patients (20%) have high HER2 over expression, 6 patients (17%) have moderate HER2 expression and 11 patients (31%) have HER2 activation (phospho positive) with no HER2 over-expression. Conclusions: When CTCs were present, the CEER assay identified varying levels of HER2 involvements in 68% of metastatic GCA patients. HER2 positive CTCs could serve as a prognostic and/or predictive marker in patients with advanced GCA and CTC-HER2 profile shifts can be utilized to monitor the treatment efficacy.

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]

Sign in / Sign up

Export Citation Format

Share Document