REVIVE study: a prospective observational study in chemotherapy after nivolumab therapy for advanced gastric cancer

2020 ◽  
Author(s):  
Yukiya Narita ◽  
Hirokazu Shoji ◽  
Sadayuki Kawai ◽  
Takuro Mizukami ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Cytotoxic Chemotherapy ◽  
Clinical Trial Registration ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Gastric Cancer Patients ◽  
To Receive

Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182.

KRAS and BRAF mutational status as response biomarkers to cetuximab combination therapy in advanced gastric cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
G. Stella ◽  
F. Rojas Llimpe ◽  
C. Barone ◽  
A. Falcone ◽  
F. Di Fabio ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Therapy ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Locally Advanced ◽  
Braf Mutations ◽  
Exon 2 ◽  
Mutational Status ◽  
Gastric Cancer Patients

e15503 Background: The prognosis of advanced gastric cancer (GC) patients (pt) is still poor despite the introduction of new chemotherapy regimens. In colorectal cancer (CRC) it has been demonstrated that KRAS or BRAF mutations are associated with resistance to treatment with the anti-EGFR mAbs. We have assessed whether, and to what extent, the mutational profile of KRAS and BRAF genes affects the response to cetuximab combination therapy in GC. Methods: We have collected 44 tumor samples from pts affected by locally advanced or metastatic GC undergoing cetuximab combination therapy as first-line treatment in two consecutive phase II studies. Thirteen pts received cetuximab plus FOLFIRI (FOLCETUX Study) and 31 pts cetuximab plus cisplatin and docetaxel (DOCETUX Study). Genomic DNA was extracted from paraffin-embedded tumor specimens from all cases. The mutational status of KRAS (exon 2) and BRAF (exon 15) was ascertained by PCR amplification followed by direct sequencing. The objective response was evaluated every 6 weeks by CT according to RECIST criteria. Results: KRAS and BRAF mutations were detected in 5 (11.4%) and 1 (2.3%), respectively, of the 44 tumors analyzed. These frequencies are consistent with those previously reported in GC. In the case of KRAS, 3 cases displayed amino acid substitutions of codon 12 and 1 of codon 13. One case had the A11V variant that had been reported in hematopoietic and lymphoid tissue of the stomach. The only BRAF mutation found in 1 sample was the classic V600E substitution. As a whole, 13.6 % of the analyzed tumors carried a mutation in either KRAS or BRAF genes. K-RAS and BRAF mutations were, as expected, mutually exclusive. In this pt cohort oncogenic activation of KRAS/BRAF-signaling pathways was not significantly associated to objective response (p= 0.757). Also, we found no correlation between KRAS/BRAF mutations and clinical outcome measured as overall survival. Conclusions: In advanced GC the frequency of mutations in KRAS and BRAF is lower as compared with CRC cancer. In our cases, the mutational status of KRAS and BRAF genes does not correlate with the response to cetuximab-based therapy in advanced gastric cancer patients. No significant financial relationships to disclose.

scholarly journals An Exploration of Trifluridine/Tipiracil in Combination with Irinotecan in Patients with Pretreated Advanced Gastric Cancer

2021 ◽  
Author(s):  
Takuro Mizukami ◽  
Keiko Minashi ◽  
Hiroki Hara ◽  
Tomohiro Nishina ◽  
Yusuke Amanuma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Abstract Background: Trifluridine/tipiracil (FTD/TPI) and irinotecan are treatment options for heavily pretreated patients with advanced gastric cancer but with limited efficacies. We investigated the combination of FTD/TPI and irinotecan for such patients.Methods: Patients who refractory to fluoropyrimidine, platinum and taxane were enrolled into four cohorts (Level 1A/1B/2A/2B) used an escalated dose of irinotecan [100 (Level 1) or 125 mg/m2 (Level 2) on days 1 and 15] with 2 schedules of FTD/TPI 35 mg/m2/dose: twice daily, on days 1-5 and 8-12 (Level A) or on days 1-5 and days 15-19 (Level B) of a 28-day cycle. The primary and secondary objectives were determination of maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) , and evaluation of disease control rate (DCR), respectively. Results: Eleven patients were enrolled; 2 at Level 1A, 3 at Level 1B and 6 at Level 2B. DLTs occurred in 2/2 patient at Level 1A, and 2/6 patients at Level 2B. Grade 3 or higher treatment-related adverse events were neutropenia (90.9%), leukopenia (54.5%), anemia (45.5%) and febrile neutropenia (18.2%). One patient at Level 2B achieved partial response and the DCR was 72.7% (95% CI 39.0- 94.0%). The median progression-free survival and overall survival was 3.0 months (95% CI 0.92- not reached) and 10.2 months (95% CI 2.2- not reached), respectively.Conclusion: The RP2D of FTD/TPI combined with irinotecan was determined to be Level 1B with manageable hematologic toxicities and feasible non-hematologic toxicities. Further evaluation for its efficacy in the RP2D is necessary. Mini-abstract: A phases Ib study of trifluridine/tipiracil in combination with irinotecan for advanced gastric cancer determined the recommended dose with manageable hematologic toxicities and feasible non-hematologic toxicities.

Analysis of predictive factors of ramucirumab plus paclitaxel for advanced gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 185-185
Author(s):  
Naoki Fukuda ◽  
Daisuke Takahari ◽  
Hiroki Osumi ◽  
Tomohiro Matsushima ◽  
Izuma Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Predictive Factors ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Independent Factor ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Gastric Cancer Patients

185 Background: Ramucirumab (RAM) is a novel anti-VEGF antibody approved in 2015 in Japan. Predictive factors for RAM in combination with paclitaxel (PTX) remain largely unknown. Methods: We reviewed 77 consecutive advanced gastric cancer patients who were treated with RAM plus PTX between June 2015 and June 2016 in our institution. We evaluated treatment outcome and analyzed potential predictive factors by univariate and multivariate analyses. Results: Median age was 67 years (range 35-83) and 51 % of the patients were male. The ECOG performance status (PS) was ≥ 2 in 8 patients. 89% (69/77) patients were treated as second line chemotherapy. Objective response rate (ORR) in patients who have measurable disease was 52 % (17/33). Median progression free survival (PFS) and overall survival (OS) and was 6.0 months (95% confidence interval [CI] = 4.3-7.1) and 10.4 months (95% CI 6.8-13.6), respectively. The most frequent adverse events were peripheral neuropathy (44%), G3 ≥ neutropenia (34%), hypertension (32%) and bleeding (27%). At multivariate analysis, hypertension was independent factor for OS (Hazard ratio [HR] = 0.35, 95% CI = 0.14-0.90, P = 0.03). Also, bleeding (HR = 0.23, 95% CI = 0.09-0.55, P = 0.001) was independent factor for PFS and hypertension (HR = 0.47, 95% CI = 0.22-1.02, P = 0.06) had trend toward to show better PFS. Conclusions: RAM plus PTX showed promising efficacy for advanced gastric cancer. RAM related toxicities such as hypertension and bleeding/hemorrhage were independent factors for better outcome. Further investigation is warranted to verify our analysis.

scholarly journals Prognostic factors in advanced gastric cancer patients receiving cytotoxic chemotherapy

1986 ◽  
Vol 111 (S1) ◽  
pp. S85-S85
Author(s):  
G. Schnitzler ◽  
J. Furkert ◽  
M. Bohrer ◽  
L. Edler ◽  
M. E. Heim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Cytotoxic Chemotherapy ◽  
Gastric Cancer Patients

Impact of Prior Ramucirumab Use on Treatment Outcomes of Checkpoint Inhibitors in Advanced Gastric Cancer Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 203-209
Author(s):  
Jinchul Kim ◽  
Seonggyu Byeon ◽  
Hyera Kim ◽  
Ja Hyun Yeo ◽  
Jung Yong Hong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Outcomes ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Gastric Cancer Patients

scholarly journals An open label, multicenter, noninterventional study of apatinib in advanced gastric cancer patients (AHEAD-G202)

2020 ◽  
Vol 12 ◽  
pp. 175883592090542
Author(s):  
Xiang Wang ◽  
Ruixing Zhang ◽  
Nan Du ◽  
Mudan Yang ◽  
Aimin Zang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
High Dose ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Grade 3 ◽  
Gastric Cancer Patients ◽  
Noninterventional Study

Background: Apatinib has been proved to be effective and well tolerated among patients in phase II and III studies. Here, we evaluated the safety and effectiveness of apatinib in advanced gastric cancer patients in a real-world setting. Methods: This study enrolled advanced gastric cancer patients who had progressed or relapsed despite systemic chemotherapy. The primary outcome was safety and the secondary outcomes included overall survival (OS) and progression-free survival (PFS). Results: A total of 337 patients were included. In total, 62 (18.4%), 102 (30.3%), and 173 (51.3%) patients received first, second, and third or higher line apatinib therapy, respectively. Grade 3/4 treatment-emergent adverse events (AEs) were infrequent (<5%), with hypertension (6.8%) being the only grade 3/4 AE occurring in more than 5% of the patients and across the low-dose (250 mg, 7.3%), mid-dose (425–500 mg, 6.1%), and high-dose group (675–850 mg, 2/15, 13.3%). The median OS and PFS were 7.13 months (95% CI, 6.17–7.93) and 4.20 months (95% CI, 4.60–4.77), respectively, and were comparable among the low-, mid-, and high-dose groups. Conclusion: Lower daily doses of apatinib achieved comparable OS and PFS versus higher daily doses of apatinib while maintaining a more benign safety profile in advanced gastric cancer patients. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02668380.

scholarly journals Immunotherapy for Peritoneal Metastases from Gastric Cancer: Rationale, Current Practice and Ongoing Trials

2021 ◽  
Vol 10 (20) ◽  
pp. 4649
Author(s):  
Eva Ruiz Hispán ◽  
Manuel Pedregal ◽  
Ion Cristobal ◽  
Jesús García-Foncillas ◽  
Cristina Caramés
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Peritoneal Metastases ◽  
Therapeutic Approaches ◽  
Current State ◽  
Metastatic Setting ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
New Strategies

Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy treatment of peritoneal dissemination. The immunogenicity of the peritoneum has been described to be particularly active at omentum and peritoneal lymph nodes. Also, both innate and acquired immunity seems to be involved at different molecular levels. Recent works show PDL1 expression being less present at the peritoneal level; however, some clinical trials have begun to yield results. For example, the ATTRACTION-2 trial has demonstrated the activity of Nivolumab in heavily pretreated patients even though peritoneal metastases were diagnosed in a 30% of them. Despite positive results in the metastatic setting, peritoneal responses to systemic checkpoint inhibitors remains unclear, therefore, new strategies for intraperitoneal immunotherapy are being proposed for different ongoing clinical trials.

Sign in / Sign up

Export Citation Format

Share Document