Treatment Of Metastatic Gastric Adenocarcinoma Research Articles

Safety and efficacy of nanosomal docetaxel lipid suspension (NDLS) in patients with advanced gastric adenocarcinoma.

348 Background: Nanosomal docetaxel lipid suspension (NDLS) was developed to overcome toxicity issues associated with conventional docetaxel. Docetaxel, cisplatin, 5-fluorouracil (5-FU; DCF) or modified DCF (mDCF) is one of the recommended first-line regimens for patients with metastatic gastric adenocarcinoma (GAC). However, majority of the patients experienced grade 3/4 toxicities with DCF regimen using conventional docetaxel. The present study evaluated the safety and efficacy of NDLS-based mDCF/DCF regimens in patients with metastatic GAC. Methods: In this multicentric, open-label, clinical trial, patients with previously untreated metastatic GAC were enrolled. Patients received either mDCF [NDLS 40 mg/m2 on day 1 (D1), C 40 mg/m2 on D2 or D3, 5-FU 400 mg/m2 bolus on D1, leucovorin 400 mg/m2 on D1, 5-FU 1000 mg/m2/day continuous infusion D1 & 2; q2w] for 9 cycles, or DCF [NDLS 75 mg/m2 on D1, C 75 mg/m2 on D1, 5-FU 750 mg/m2/day for 5 days given as continuous infusion; q3w] for 6 cycles. Prophylactic GCSF (Granulocyte Colony Stimulating Factor)/Peg-GCSF support was allowed in all patients. The primary endpoint was overall response rate (ORR) at week 18. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety outcomes. Patients were followed up to 1 year. Results: Fifty-two patients were enrolled, with mean (±SD) age of 52 (±9.6) years & male:female ratio of 32:20. Thirty-eight patients qualified for modified intent-to-treat (mITT) analysis for efficacy evaluation (mDCF: 33; DCF:5). At week 18, ORR was 57.9% & DCR was 81.6% in mITT population. In the per-protocol population (n=26), ORR was 61.5% at 18 weeks (mDCF:63.6%; DCF:50%). Safety set included all 52 patients. Any grade adverse events (AEs) were reported in 90.4% (n=47) of the patients; with 40.4% experiencing grade 3/4 AEs. All-grade AEs reported in ≥10% of the patients included anemia, neutropenia, abdominal pain, diarrhea, nausea, vomiting, fatigue, mucositis, decreased appetite, peripheral neuropathy; with majority of AEs being grade 1/2. Most common grade 3/4 AE was neutropenia; observed in 17.3% (n=9) patients (mDCF: 14%; DCF: 33.3%). Conclusions: NDLS-based regimens demonstrated efficacy & improved safety profile in the treatment of metastatic GAC. Clinical trial information: CTRI/2018/01/011450 . [Table: see text]

SY17-4 Immuno-oncology agents for advanced gastric cancer

The treatment of metastatic gastric adenocarcinoma remains challenging. The management typically consisted of the use of combination cytotoxic agents in various lines of treatment, trastuzumab in combination with chemotherapy in the first line treatment of HER2 positive gastric adenocarcinoma and ramucirumab ± paclitaxel in the second line treatment. Recently progress has been made in the management of gastric cancer with the introduction of the anti-PD antibodies nivolumab and pembrolizumab. The data on nivolumab and pembrolizumab ± chemotherapy in first line and in pretreated and/or chemorefractory are interesting and open perspectives for improved outcome and for prolonged survival in selected patients. The introduction of the anti-PD antibodies will shape our new treatment algorithms and guidelines. Optimal clinical and molecular selection is necessary in order to optimize the use of these checkpoint inhibitors. The data on the selection for CPI through predictive biomarkers, such MSI-H/MSS status, PDL CPS scoring, EBV staining and TMB are important to the use of CPI. The various situations and indications, in which CPI have been and are still studied will be discussed: early lines of treatment of metastatic gastric cancer, pretreated and chemorefractory and maintenance treatment. In the future the anti-PD/anti-PDL antibodies may be combined with other immuno-oncology agents, such as CTLA-4 antibodies and new classes of immuno-oncology agents, but also with other targeted agents such as e.g. anti-HER2 targeting agents and PARP inhibitors.

Clinical response and biomarker analysis of a phase II basket trial of toripalimab, a PD-1 mAb in combination with standard chemotherapy as a first-line treatment for patients with solid tumors.

e15083 Background: Platinum based chemotherapy is the standard care for 1st line treatment of metastatic gastric adenocarcinoma (GC), esophageal squamous cell carcinoma (ESSC), nasopharyngeal carcinoma (NPC) and head and neck squamous cell carcinoma (HNSCC). Combinations of PD-1 blockade with chemotherapy have shown promising but mixed results in solid tumors. Predictive biomarkers for chemo-immunotherapy combination as 1st line treatment remain undefined. Methods: Patients (n = 60) included in this analysis were four complete cohorts from a multi-center, phase Ib/II trial (NCT02915432) evaluating the safety and activity of toripalimab, a humanized PD-1 antibody in combination with standard chemotherapy for the 1st line treatment of GC, EC, NPC and HNSCC (excluding NPC). Whole exome sequencing (WES), RNA sequencing and immunohistochemistry were performed on tumor biopsy samples. PD-L1 expression and tumor mutational burden (TMB) were evaluated for correlation with clinical efficacy. Results: From Oct 2016 to Feb 2019, 33 GC, 12 ESSC, 12 NPC and 3 HNSCC patients were enrolled and treated with 240mg or 360 mg toripalimab Q3W via IV infusion in combination with Oxaliplatin/Capecitabine (XELOX), Paclitaxel/Cisplatin (PP), Gemcitabine/Cisplatin (GP) and Docetaxel/Cisplatin/5-FU(TPF) respectively. By the data cutoff date of Nov 15, 2019, all patients experienced treatment related adverse event (TRAE). There was one TRAE (heart failure) leading to death. Grade 3-4 TRAEs occurred in 67% patients, mostly attributed to chemotherapy, including 27% neutropenia, 23% thrombocytopenia, 18% leukopenia and 12% anemia. As assessed by investigators according to RECIST v1.1, the ORR/DCR were 54.5%/84.8%, 66.7%/91.7%, 75.0%/83.3% and 33.3%/100% respectively for GC, EC, NPC and HSNCC cohorts. The median duration of response was 8.3, 6.8, 7.7 and 7.1 months respectively. WES showed distinctive patterns of genomic alterations among different cohorts. The clinical response was not correlated with either PD-L1 expression or tumor mutational burden. Conclusions: Toripalimab in combination with chemotherapy as first-line treatments showed promising results for metastatic GC, EC, NPC and HNSCC patients. Two randomized Phase III trials of toripalimab in combination with Paclitaxel/Cisplatin or Gemcitabine/Cisplatin versus chemotherapy alone are ongoing to further evaluate the combination as first-line treatments in metastatic EC and NPC patients. Clinical trial information: NCT02915432 .

Survival outcomes with docetaxel, oxaliplatin, and fluorouracil regimen for the treatment of metastatic gastric adenocarcinoma: A single-center experience

Background: Patients with metastatic gastric adenocarcinoma have a relatively poor prognosis with a median survival of 6 months. The three-drug regimen of docetaxel, oxaliplatin, and fluorouracil (DOF) has been shown to improve survival compared to the two-drug regimen of docetaxel and oxaliplatin with similar toxicity. However, there is no published Indian experience with this regimen. Aim: The aim of this study was to evaluate the efficacy in terms of progression-free survival (PFS) and overall survival (OS) of DOF regimen for metastatic gastric adenocarcinoma patients in Indian settings. Materials and Methods: All patients with metastatic gastric adenocarcinoma who were treated with DOF regimen chemotherapy at our tertiary care center in North India from 2014 to 2018 were retrospectively reviewed. The DOF regimen consisted of docetaxel 50 mg/m2 on day 1, followed by oxaliplatin 85 mg/m2 on day 1, and 5-FU 2400 mg/m2 continuous intravenous infusion over 46 h; (cycle repeated at two weekly intervals until progression or unacceptable toxicity). The endpoints were overall response rate (ORR), PFS, and OS, which were evaluated using Kaplan–Meier analysis. Results: Fifteen patients with a median age of 52 years were identified; 73% were male. ORR was seen in 86.7% of patients (complete response: 20%, partial response: 60%, and stable disease: 6.7%) and progressive disease was seen in 13.3% of patients. With a median follow-up of 14 months, the median PFS was 7 months and the median OS was 16 months from the start of therapy. One-year PFS was 22% and 1- and 2-year OS was 79% and 26%, respectively. The most frequent Grades 3–4 adverse events in our patients being mucositis (33.3%), neutropenia (26.7%), and diarrhea (20%). Conclusion: DOF regimen is an effective and feasible regimen in patients with metastatic gastric cancer.

Treatment of metastatic gastric adenocarcinoma with image-guided high-dose rate, interstitial brachytherapy as second-line or salvage therapy.

We aimed to evaluate the safety and effectiveness of image-guided high-dose rate interstitial brachytherapy (iBT) for the treatment of patients with hepatic, lymphatic, and pancreatic metastases originating from gastric cancer, an entity rarely surgically treatable with curative intent. Twelve patients with a cumulative number of 36 metastases (29 liver, 2 pancreatic, 5 lymph node) from histologically proven gastric adenocarcinoma received iBT between 2010 and 2016 and were retrospectively analyzed. Every patient underwent palliative chemotherapy prior to iBT. The iBT procedure employs a temporarily, intratumorally placed iridium-192 source in a single fraction with the goal of tumor cell eradication. Effectiveness was assessed clinically and by radiologic imaging every three months. Local tumor control was achieved in 32 of all treated metastases (89%). Four lesions showed a local recurrence after 7 months. Lesion sizes varied from 9 to 102 mm with a median of 20 mm. The median progression-free survival was 6.6 months (range, 1.8-46.8 months). The median overall survival was 11.4 months (range, 5-47 months). One patient suffered a major complication following iBT, hepatic hematoma and abscess (Common Terminology Criteria for Adverse Events grade 3), successfully dealt with by transcutaneous drainage. iBT is an overall safe procedure, which facilitates high rates of local tumor control in treatment of metastatic gastric adenocarcinoma. Compared with surgical metastasectomy, similar overall survival rates could be achieved in our patient collective after iBT application.

318. A systematic review of the role of hepatectomy in the treatment of metastatic gastric adenocarcinoma

318. A systematic review of the role of hepatectomy in the treatment of metastatic gastric adenocarcinoma

RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors.

4076 Background: RAINBOW, a global, randomized, double-blind, phase 3 trial demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and response rate in met...

Chemoimmunotherapy in the treatment of metastatic gastric cancer

Docetaxel, capecitabine and 5-fluorouracil have been shown to be active in the treatment of metastatic gastric adenocarcinoma. Consistent with this finding, the aim of this study was to test this combination in a clinical trial. Forty-one patients with metastatic gastric adenocarcinoma and a median age of 64 years were recruited for the study. The treatment was based on the administration of docetaxel 60 mg/m2 every 4 weeks, leucovorin 200 mg/m2, 5-fluorouracil 400 mg/m2 bolus, and capecitabine 1000 mg/m2 twice daily on days 1 and 2 every 2 weeks. Patients achieving a clinical benefit were treated, as maintenance immunotherapy, with low-dose interleukin-2 and 13-cis-retinoic acid. The primary end point of this phase II study was the response rate. The secondary end points relied on the evaluation of the immunological parameters, toxicity, and progression-free survival and overall survival. The overall response rate in the 41 evaluable patients was estimated to be 49%. Median progression-free and overall survival was 9.5 and 21.1 months, respectively. Grade 3 and 4 hematological toxicities were neutropenia and thrombocytopenia in 44 and 5% of patients, respectively. A sustained improvement of evaluated immunological parameters with a negligible toxicity profile was observed in the 27 patients treated with interleukin 1-2/13-cis-retinoic acid. Docetaxel in combination with leucovorin, 5-fluorouracil and capecitabine followed by low-dose interleukin 1-2 and 13-cis-retinoic acid is well tolerated, and shows a significant activity in patients with metastatic gastric adenocarcinoma.