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.

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

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4050-4050
Author(s):  
Hongli Li ◽  
Jingyu Deng ◽  
Shaohua Ge ◽  
Fenglin Zang ◽  
Le Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Death Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

A phase II study of efficacy and safety of RC48-ADC in patients with locally advanced or metastatic HER2-overexpressing gastric or gastroesophageal junction cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4560-4560 ◽  
Author(s):  
Zhi Peng ◽  
Tianshu Liu ◽  
Jia Wei ◽  
Airong Wang ◽  
Yifu He ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Her2 Overexpression ◽  
Efficacy And Safety ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Microtubule Inhibitor ◽  
Eligibility Criteria

4560 Background: RC48-ADC is an antibody-drug conjugate (ADC) drug comprised of a novel humanized anti-HER2 IgG1, a linker, and a microtubule inhibitor, MMAE. The MoA included inhibition of HER2 signal pathway and cytotoxicity of MMAE. RC48-ADC has demonstrated promising anti-tumor activity in pre-clinical and early clinical studies. The current study is designed to evaluate the efficacy and safety of RC48-ADC in heavily treated patients with HER2-overexpressing (IHC 2+ or 3+) gastric or gastro-esophageal junction cancers. Methods: This is an open-label, multicenter, single-arm, phase II study. Eligibility criteria include: histologically confirmed gastric or gastro-esophageal junction cancers, HER2-overexpression (IHC 2+ or 3+), ECOG PS 0-1, post-to ≥2 prior systemic treatment. The patients received RC48-ADC, 2.5 mg/kg, q2w until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was ORR. PFS, OS, and safety were also evaluated. Results: Patient enrollment started in July 2017, and completed in November 2019. By the data cut-off date on 17-Dec-2019, 127 patients were enrolled. The median age was 58 years. At baseline, 59 patients (46.5%) had received ≥ 3 lines prior treatment. For the overall 127 patients, the investigator-assessed confirmed ORR was 18.1% (95% CI: 11.8%, 25.9%). Sub-group ORR was 19.4% and 16.9% for the patients post to 2 lines and ≥ 3 lines, respectively. For the 111 patients who were monitored for ≥ 2 cycles of efficacy assessments (i.e. 12 weeks), the ORR was 20.7% (95% CI: 13.6%, 29.5%). For the 127 patients, the mPFS was 3.8 months (95% CI: 2.7, 4.0, 89 events [70.1%]) and the mOS was 7.6 months (95% CI: 6.6, 9.2, 52 events [40.9%]). The most commonly reported treatment-related AEs were leukopenia (52.0%), alopecia (51.2%), neutropenia (48.0%), and fatigue (42.5%). Conclusions: RC48-ADC demonstrated a clinically meaningful response and survival benefit in the heavily treated patients with HER2-overexpressing gastric or gastro-esophageal junction cancers. The safety profile was in line with the previously reported data of RC48-ADC. RC48-ADC showed positive benefit/risk ratio for the target population. Clinical trial information: NCT03556345 .

Phase II study of trifluridine/tipiracil (FTD/TPI) and oxaliplatin as induction chemotherapy (IC) in resectable esophageal and gastroesophageal junction adenocarcinoma (EGAC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS464-TPS464
Author(s):  
Sarbajit Mukherjee ◽  
Hussein Assi ◽  
Christos Fountzilas ◽  
Kristopher Attwood ◽  
Patrick McKay Boland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Metabolic Response ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Fixed Dose ◽  
Open Label ◽  
Ecog Performance Status ◽  
Total N

TPS464 Background: Neoadjuvant chemoradiation (CRT) followed by surgery is a standard approach for localized EGAC. Despite multimodality treatment, 5-year overall survival (OS) is less than 50%, with pathologic complete response (pCR) rates of 20%. Achievement of pCR is associated with an improved OS. We propose to use a novel combination of FTD/TPI and oxaliplatin as IC. We hypothesize that IC before CRT will increase the pCR rate in localized EGAC. Methods: This is an open-label, multicenter phase II trial. Patients (pts) with potentially resectable loco-regional EGAC are eligible. Pts. should have adequate organ function, ECOG performance status of 0 –1, age < 76 years, and endoscopic ultrasound-determined node-positive disease with any T-stage, or T3-T4a with any N stage. Pts. with T4b or M1 disease will be excluded. Pts. will receive three cycles of IC with FTD/TPI and oxaliplatin. Based on the maximum tolerated dose (MTD) observed in a phase I trial, FTD/TPI will be administered 35 mg/m² BID, days 1–5 every 14 days, with a fixed dose of oxaliplatin 85 mg/m² (day 1). Pts will then undergo concurrent CRT (standard radiation dose of 5040 cGY will be utilized) with weekly Carboplatin (AUC 2) and Paclitaxel (50 mg/m2) for 6 weeks followed by surgery. Our primary objective is to evaluate the pCR rate. The secondary objectives include evaluation of 2-year disease-free survival (DFS), 2-year OS, and assessment of toxicities of the IC. As a correlative endpoint, circulating tumor DNA level will be correlated with disease recurrence and metabolic response on PET CT. Assuming a historic pCR rate of 20% with standard CRT, 41 pts (enrollment of up to 45 pts accounting for non-evaluable pts) are needed to show a 15% increase in pCR with IC with 80% power at one-sided significance level of α = 0.1. In stage 1, n1= 22 evaluable pts will be enrolled. If there is 5 or more pCRs, an additional n2= 19 pts will be enrolled in stage 2. If 12 or more pCRs are observed in the total n = 41 evaluable pts, then the proposed treatment regimen will be considered promising for further study. We anticipate accrual over a 2-year period from 3 sites. Clinical trial information: NCT04097028.

scholarly journals HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001279
Author(s):  
Yan Song ◽  
Ning Li ◽  
Qun Li ◽  
Xinjun Liang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Gastroesophageal Junction Cancer

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3330-3337 ◽  
Author(s):  
Marianne Sinn ◽  
Marcus Bahra ◽  
Torsten Liersch ◽  
Klaus Gellert ◽  
Helmut Messmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Open Label ◽  
Term Survival

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

PET-directed combined modality therapy for gastroesophageal junction cancer: First results of the prospective MEMORI trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4018-4018 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Michael Quante ◽  
Isabel Rauscher ◽  
Julia Slotta-Huspenina ◽  
Karl Friedrich Becker ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Combined Modality Therapy ◽  
Gastroesophageal Junction ◽  
Disease Free Survival ◽  
Multicenter Trial ◽  
Primary Objective ◽  
R0 Resection ◽  
Gastroesophageal Junction Cancer ◽  
First Results ◽  
Pathologic Complete Remission

4018 Background: We evaluated a PET-guided treatment stratification for improvement in obtaining negative surgical margins (R0) in resectable gastroesophageal junction (GEJ) adenocarcinoma. According to sequential 18F-FDG PET, only 40–50% of patients (pts) respond to neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT). Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in this interventional, prospective, non-randomized multicenter trial. Pts underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (physicians’ choice, e.g. EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders (P-R), defined as ≥ 35% decrease in SUVmax from baseline, continued with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly carboplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT. Primary objective was an improvement of R0 resection rates in P-NR above a proportion of 70% based on results from the MUNICON1/2 trials. Secondary endpoints include disease-free survival (DFS), overall survival (OS), measured from randomization to death from any cause, and translational endpoints. Results: Between 12/2014 and 07/ 2018 160 pts with resectable GEJ adenocarcinomas were prospectively screened with PET in three German university centers. Overall, 85 pts (53%) could not be included due to previously undetectable metastases (40/25%), no or too low FDG uptake of the primary tumor (21/13%), other reasons (24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable. Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respectively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for P-NR. Pathologic complete remission (pCR; < 10% vital tumor cells), was 33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75% for P-NR. Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0- and pCR rates among pts who were P-NR after induction CTX. PET response was prognostic for a prolonged OS and DFS. Clinical trial information: 2014-000860-16.

scholarly journals Induction therapy with Erlotinib (E) and Gemcitabine/Platinum (GP) in stage III NSCLC

2021 ◽  
Vol 5 (1) ◽  
pp. 001-018
Author(s):  
Overbeck Tobias R ◽  
Wenleder Stefan HP ◽  
Danner Bernhard C ◽  
Körber Wolfgang ◽  
Toepelt Karin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Induction Therapy ◽  
Molecular Mechanisms ◽  
Egfr Mutation ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Stage Iii ◽  
Open Label ◽  
Disease Free

Background: In 2004 we started a phase II trial in non-small lung cancer (NSCLC), stage III, with erlotinib followed by a combination with a platinum-based doublet in unselected patients to identify molecular subgroups benefitting from an EGFR targeting approach. Patients and methods: Induction with erlotinib (E, 150 mg, d1-42) was followed by three cycles of gemcitabine (G, 1250 mg/m², d1+d8, q3w) and cisplatin (P, 80 mg/m², d1, q3w). Patients with at least stable disease after E were treated with a GP + E combination. Induction was followed by surgery and radiation. The trial was conducted as a prospective, multi-center, open label, exploratory phase II study to determine pathological response rate (pRR), as well as secondary endpoints disease free survival (DFS) and overall survival (OS). Results: Of 38 prescreened patients 16 were included in the main study. Due to slow recruitment the study had to be terminated early. Combination of E and GP was well tolerated, surgery was feasible after induction therapy in 12 of 16 patients, 7/12 (58%) patients had a major pathological response (MPR). Median overall survival for patients with MPR was 57.7 months (confidence interval (CI), 37.4 to 78.0; n = 7) and for patients without MPR 11.9 months (CI, 6.4 to 17.4; n = 5). 2/16 patients had an epidermal growth factor receptor (EGFR) mutation. Conclusion: Before discovery of distinct molecular mechanisms in NSCLC our study was an attempt to identify clinical and pathological subgroups that would benefit from E induction. Two patients with an EGFR mutation were identified. MPR was a predictor of long term disease free and overall survival.

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