Clinicopathological characteristics of patients with HER2-positive gastric and gastroesophageal junction cancer in a single tertiary hospital.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16105-e16105
Author(s):  
Efrain Isaias Camarin Sanchez ◽  
Ervin Saúl Enciso López ◽  
Benigno Rodriguez ◽  
Diana Alejandra Villegas Osorno ◽  
Omar Serrano Villamayor ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Stage ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Female Ratio ◽  
Gastroesophageal Junction Cancer ◽  
Her 2

e16105 Background: Gastric cancer (GC) and gastroesophageal junction cancer (GEJ) are the second most prevalent and lethal digestive malignancies worldwide. According to GLOBOCAN 2020, the incidence in Mexican population is 4.5% and represents 7% of all deaths. In GC and GEJ, the frequency of HER2 overexpression varies widely in the literature. Actually the blocking anti-HER2 is the standard therapy in GC and GEJ with overexpression HER2 according to the ToGa Trial. There are few studies that describe this population in mexican patients. Methods: We conducted a retrospective, observational analysis. Medical records of patients with GC or GEJ cancer from January 2015 to January 2021 were reviewed. A total of 91 patients were retrieved from the pathology database. Clinicalpathologic features collected were sex, age, pTNM stage (AJCC 8th edition), histology type, HER-2 status, metastases sites and treatment. The HER-2 determination was performed in all cases with immunohistochemistry (IHQ). Results: We found 10 patients with GC and GEJ with HER-2 overexpression by IHC, five patients with FISH positive and 2 of them with amplification by next generation sequence (FoundationOne). The median age was 56.9 years (27-68). There were more male patients (n = 8) than female patients (n = 2), with male/female ratio of 4:1. 8 patients had performance status (PS) 0 or 1, and the rest PS 2. The primary site was gastric carcinoma in 3 patients, and in 7 the tumor was located in GEJ. The clinical stage at diagnosis in 7 patients was metastatic, and 3 locally advanced. The most common sites of metastasis were lung (n = 5), liver (n = 4), and pleural, bone and central nervous system (each one with one patient). Intestinal-type GCs were most prevalent with 8 patients, and the rest were diffuse and signet ring cells. All patients received anti-HER2 blockade, 6 in the first line therapy, and 4 patients in the second line or more. Regarding the backbone regimen of the trastuzumab based therapy, fluoropyrimidine/platinum were the mainstay in 9 patients, and 1 with platinum and taxane scheme. Median number of cycles of trastuzumab was 8 (range, 4-24). The tumor responses were as follows: complete response (CR) 10%, partial response (PR) 30%, stable disease 50% and progressive disease 1 patient. The median progression-free survival was 6.6 months (1.3-23.1 months), and a median of overall survival was 21 months (6.4-51.5 months). The most frequently reported adverse events were diarrhoea in 3 patients (all grade 2), and mucositis in 1 patient. Cardiac adverse events were not reported. Conclusions: In our cohort, the prevalence of HER2 overexpression by IHC was 11%. In previous reports, the most important ToGa trial, 22% of the patients with metastatic GC and GEJ were HER2 positive. The PFS and OS in ToGa trial were 13.8 and 17.1 months respectively. By comparison our cohort the PFS and OS in ToGa trial were 6.6 and 21 months.

The preliminary efficacy of KN026 (Anti-HER2 BsAb) in advanced gastric and gastroesophageal junction cancer patients with HER2 expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16005-e16005
Author(s):  
Jianming Xu ◽  
Yun Zhang ◽  
Jun Wu ◽  
Nong Xu ◽  
Jieer Ying ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Drug Exposure ◽  
Gastroesophageal Junction ◽  
Ureteral Stricture ◽  
Her2 Overexpression ◽  
Line Treatment ◽  
Her2 Positive ◽  
Gastroesophageal Junction Cancer ◽  
Low Expression

e16005 Background: HER2 overexpression or amplification has been proven to be a validated therapeutic target for HER2-positive gastric and gastroesophageal junction cancer (GC/GEJ) in ToGA trial. However, there is a huge unmet medical need in the HER2-positive GC/GEJ patients who progressed or were refractory to trastuzumab treatment. In HER2 low expression patients, the benefit of novel HER2-targeted therapeutics, eg. Bispecifics, ADC and CAR-T, remain to be explored. Here we report the preliminary results of KN026, a bispecific antibody binds two distinct epitopes of HER2 receptors, in GC/GEJ patients with prior at least one line treatment. Methods: GC/GEJ patients who failed to ≥first-line treatment were enrolled into two cohorts according to HER2 overexpression (Cohort 1: IHC3+ or IHC 2+ ISH+) and low expression (Cohort 2: IHC 1+/2+ ISH- or IHC 0/1+ISH+), and treated by KN026 QW10mpkor Q2W(20mpk) or Q3W(30mpk) until progression of disease (PD) or intolerable toxicity or 2 years. Results: As of 2020/12/25, a total of 31 pts received KN026 treatment including 20 pts in Cohort 1 and 11 pts in Cohort 2. The median drug exposure period was around 20 wks and 6 wks in two Cohorts, respectively. Among 18 efficacy-evaluable pts in Cohort 1, 11 pts were stilling receiving treatment with 55.6% (10/18) ORR and 72.2% DCR (13/18). The 9-m PFS rate was 60.4% (95%CI: 24.4 to 83.5) in Cohort 1, while the DOR, mPFS and mOS were not reached. Of 9 pts receiving prior-HER2 treatment, the median time from the first dose of KN026 to last prior HER2 treatment was 55 days. The ORR was 44.4% (4/9) with 4.1m DoR, and DCR was 66.7% (6/9). The mPFS and mOS were 5.6m(95%CI:1.3 to NE) and 11.0m(95%CI: 1.4 to NE), respectively. In Cohort 2, two partial response was observed out of 9 efficacy-evaluable pts. The ORR and DCR were both 22.2% (2/9) with 1.4 m mPFS (95%CI: 1.0 to 5.9) and 9.6m mOS (95%CI: 3.0 to NE). The overall incidence of KN026 related adverse events was 87.1%, with 9.7% Gr 3 TRAE. The most common KN026-related treatment emergent adverse events (≥10% TRAE) were aspartate aminotransferase increased (n=8,25.8%), rash (n=6,19.4%), anaemia (n=5,16.1%),alanine aminotransferase increased (n=4, 12.9%) and weight decreased(n=4, 12.9%). The ≥Gr 3 TEAE that KN026 related were infusion related reaction(n=1, 3.2%), blood pressure increased (n=1, 3.2%), ureteral stricture with hydronephrosis (n=1, 3.2%). Conclusions: KN026 demonstrated promising efficacy in HER2 overexpressing GC/GEJ pts and in anti-HER2 treated GC/GEJ pts with a favorable safety profile. Clinical trial number: NCT03925974. Clinical trial information: NCT03925974.

scholarly journals A Phase Ii Study Of The Combination Of Oxaliplatin, Capecitabine, And Trastuzumab And Chemo-radiotherapy In The Adjuvant Setting In Operated Patients With Her2+ Gastric Or Gastroesophageal Junction Cancer (Toxag Study), A Turkish Oncology Group Study

2020 ◽  
Author(s):  
Huseyin Abali ◽  
Suayib Yalcin ◽  
Huseyin Cem Onal ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Disease Free Survival ◽  
R0 Resection ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Open Label ◽  
Gastroesophageal Junction Cancer ◽  
Gastroesophageal Junction Adenocarcinoma

Abstract BackgroundTrastuzumab prolonged the overall survival in patients with advanced gastric cancer with HER2 overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2 + gastric carcinoma was investigated. MethodsThe patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection were included. They received 3 cycles of oxaliplatin (100 mg/m2 IV day 1) plus capecitabine (850 mg/m2 PO days 1-14), trastuzumab (8 mg/kg IV day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.ResultsOf the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (Min-max: 35-75), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the AEs were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhoea (2, 5.9%) and weight loss (N=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thrombo-embolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 65.7%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.ConclusionsTrastuzumab in combination with capecitabine, oxaliplatin and radiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease.

Pembrolizumab plus chemotherapy for previously untreated, HER2-negative unresectable or metastatic advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: KEYNOTE-859.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS263-TPS263
Author(s):  
Josep Tabernero ◽  
Yung-Jue Bang ◽  
Eric Van Cutsem ◽  
Charles S. Fuchs ◽  
Yelena Y. Janjigian ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Treatment Withdrawal ◽  
First Line ◽  
Serious Adverse Events ◽  
End Points ◽  
Expression Status

TPS263 Background: For patients with unresectable, locally advanced recurrent or metastatic G/GEJ cancer, the standard of care includes a fluoropyrimidine plus a platinum-based agent as first-line therapy. The PD-1 inhibitor pembrolizumab has demonstrated durable antitumor activity in this patient population across lines of therapy. Herein, we describe the randomized, double-blind, phase 3 KEYNOTE-859 trial (NCT03675737) of first-line pembrolizumab plus chemotherapy in patients with advanced G/GEJ adenocarcinoma. Methods: Patients with histologically or cytologically confirmed, locally advanced unresectable or metastatic G/GEJ adenocarcinoma with known PD-L1 expression status, HER2-negative disease, measurable disease per RECIST v1.1, and ECOG performance status of 0 or 1 will be randomly assigned 1:1 to receive pembrolizumab plus chemotherapy or placebo plus chemotherapy. Randomization will be stratified by geographic region (Europe/Israel/North America/Australia vs Asia vs rest of world), PD-L1 tumor expression status (combined positive score < 1 vs ≥1), and combination chemotherapy (FP vs CAPOX). Pembrolizumab or placebo will be administered at 200 mg IV every 3 weeks (Q3W). The chemotherapy regimen will be investigator’s choice of FP (continuous infusion of 5-fluorouracil [800 mg/m2/day on days 1-5 of each cycle] plus IV cisplatin [80 mg/m2] Q3W) or CAPOX (oral capecitabine [1000 mg/m2 twice daily on days 1-14 of each cycle] plus IV oxaliplatin [130 mg/m2 on day 1 of each cycle] Q3W). Duration of cisplatin or oxaliplatin may be capped at 6 cycles per local country guidelines; treatment with 5-fluorouracil or capecitabine may continue per protocol. Treatment with pembrolizumab or placebo will continue for ≤35 administrations (~2 years) or until disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, investigator decision, or noncompliance. Imaging will be performed at screening and subsequently every 6 weeks until disease progression, start of new anticancer treatment, withdrawal of consent, or death. Adverse events will be monitored throughout the study from the time of randomization to 30 days after the last dose of study treatment (90 days for serious adverse events). The dual primary end points are OS and PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary end points include ORR and DOR per RECIST v1.1 as assessed by BICR, safety, and tolerability. Enrollment is ongoing. Clinical trial information: NCT03675737.

scholarly journals Pertuzumab plus trastuzumab and chemotherapy for Japanese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subgroup analysis of the JACOB trial

2019 ◽  
Vol 25 (2) ◽  
pp. 301-311
Author(s):  
Kohei Shitara ◽  
Hiroki Hara ◽  
Takaki Yoshikawa ◽  
Kazumasa Fujitani ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Adverse Events ◽  
Subgroup Analysis ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Phase Iii ◽  
Her2 Positive ◽  
Serious Adverse Events ◽  
Gastroesophageal Junction Cancer

Abstract Background The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. Methods Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. Results A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8–not evaluable) and 15.6 months (95% CI 9.7–19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37–1.10]). Median progression-free survival was 12.4 months (95% CI 6.1–14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3–8.1) in the placebo arm (HR 0.50 [95% CI 0.30–0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. Conclusions Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.

scholarly journals Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami
Keyword(s):  
Gastroesophageal Junction ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Gastroesophageal Junction Cancer ◽  
Development Of Resistance ◽  
Epidermal Growth ◽  
Antibody Drug

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.

Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

2011 ◽  
Vol 13 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Cristina Grávalos ◽  
Carlos Gómez-Martín ◽  
Fernando Rivera ◽  
Inmaculada Alés ◽  
Bernardo Queralt ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
First Line ◽  
Her2 Positive ◽  
First Line Therapy ◽  
Gastroesophageal Junction Cancer ◽  
Line Therapy

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

scholarly journals A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan Schneider ◽  
Susan M. Perkins ◽  
Heather N. Burney ◽  
Pashtoon Murtaza Kasi ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Phase Ii ◽  
Residual Disease ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
M2 Macrophages ◽  
Activated T Cells ◽  
Trimodality Therapy ◽  
Surgical Specimen

BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56–84%) with median RFS of 21 months (95% CI, 14–40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05–0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15–0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.

Sign in / Sign up

Export Citation Format

Share Document