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.

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.

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

scholarly journals An update on the role of daratumumab in the treatment of multiple myeloma

2016 ◽  
Vol 8 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Caitlin Costello
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Blood Compatibility ◽  
Daily Practice ◽  
Combination Strategies ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Phase Ii And Iii ◽  
Future Plans

Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials. The general tolerability of mAbs has allowed for widespread investigation and use of DARA among a variety of MM patients, however their use requires special consideration. Infusion-related reactions (IRRs), interference with blood compatibility assays and response assessments are all unique factors related to the use of DARA. This review provides an update of the results from the DARA clinical trials conducted to date, its future plans for investigation, and practical management considerations for the use of DARA in daily practice.

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.

WJOG10517G: a multicenter Phase II study of mFOLFOX6 in gastric cancer patients with severe peritoneal metastases

2020 ◽  
Vol 16 (20) ◽  
pp. 1417-1424
Author(s):  
Toshiki Masuishi ◽  
Takako Eguchi Nakajima ◽  
Kentaro Yamazaki ◽  
Shuichi Hironaka ◽  
Chiho Kudo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Oral Intake ◽  
Peritoneal Metastases ◽  
Modified Folfox6 ◽  
Gastric Cancer Patients ◽  
New Treatments

Gastric cancer patients with severe peritoneal metastases, defined as massive ascites and/or inadequate oral intake, have been excluded from clinical trials of new treatments due to poor prognosis and tumor-related complications, such as ileus. Based on the results of the JCOG1108/WJOG7312G study, their prognosis when treated with 5-fluorouracil/ l-leucovorin or 5-fluorouracil/ l-leucovorin plus paclitaxel remained extremely poor in this setting. Retrospective studies have shown the promising efficacy of the modified FOLFOX6 (mFOLFOX6) regimen, with improved ascites and oral intake. Therefore, we planned a Phase II study of mFOLFOX6 in gastric cancer patients with severe peritoneal metastases (jRCTs041180007). The primary end point is overall survival, with an exploratory analysis comparing the findings with those of the JCOG1108/WJOG7312G study using Bayes' theorem. Trial registration Identifier: jRCTs041180007 (jRCTs: the Japan Registry of Clinical Trials).

HER2 in metastatic colorectal cancer: a new to target to remember

2021 ◽  
Vol 15 (2) ◽  
pp. 133-136
Author(s):  
Lynn Bitar ◽  
Joseph Zouein ◽  
Fady Gh Haddad ◽  
Roland Eid ◽  
Hampig R Kourie
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Disease ◽  
Checkpoint Inhibitors ◽  
Her2 Overexpression ◽  
Standard Chemotherapy ◽  
Common Cause ◽  
Heavily Pretreated ◽  
Pretreated Patients

Metastatic colorectal cancer is the second most common cause of cancer death. Standard chemotherapy in combination with targeted therapies represent the backbone for the treatment of advanced disease. However, options are limited for patients progressing on these regimens. Genetic testing can offer patients the opportunity to benefit from novel therapies, namely immune checkpoint inhibitors in microsatellite instability-positive tumors. HER2 overexpression has recently emerged as a potentially targetable tumor marker in colorectal cancer (CRC). Despite the absence of approvals for anti-HER2 therapies in CRC, many agents such as trastuzumab and pertuzumab were tested and demonstrated significant antitumor activity, even in heavily pretreated patients. Early trials are also evaluating lapatinib, T-DM1, tucatinib and other anti-HER2 agents in patients with metastatic CRC, with promising results.

scholarly journals Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

2018 ◽  
Vol 8 (1) ◽  
pp. 15 ◽  
Author(s):  
◽  
◽  
Keyword(s):  
Viral Vectors ◽  
Checkpoint Inhibitors ◽  
Alkylating Agents ◽  
Pharmaceutical Formulations ◽  
Molecular Classification ◽  
In Vitro Models ◽  
Therapeutic Approaches ◽  
New Strategies

Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to refine in vivo and in vitro models with the specific goal of finding new molecular aberrant pathways, suitable to be targeted by a variety of therapeutic approaches, including novel pharmaceutical formulations and immunotherapy strategies. In this review, we will first discuss current molecular classification based on genomic and transcriptomic criteria. Also, the state of the art in current clinical practice for glioblastoma therapy in the light of the recent molecular classification, together with ongoing phases II and III clinical trials, will be described. Finally, new pharmaceutical formulations such as nanoparticles and viral vectors, together with new strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy agents, such as checkpoint inhibitors, will also be discussed.

scholarly journals The Immunotherapy Landscape in Adrenocortical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2660
Author(s):  
Guillaume J. Pegna ◽  
Nitin Roper ◽  
Rosandra N. Kaplan ◽  
Emily Bergsland ◽  
Katja Kiseljak-Vassiliades ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Vaccine ◽  
Clinical Activity ◽  
Autologous Tumor ◽  
Early Stage Disease ◽  
Metastatic Setting ◽  
Wide Range

Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland that is frequently associated with excess production of adrenal hormones. Although surgical resection may be curative in early-stage disease, few effective therapeutic options exist in the inoperable advanced or metastatic setting. Immunotherapies, inclusive of a broad array of immune-activating and immune-modulating antineoplastic agents, have demonstrated clinical benefit in a wide range of solid and hematologic malignancies. Due to the broad activity across multiple cancer types, there is significant interest in testing these agents in rare tumors, including ACC. Multiple clinical trials evaluating immunotherapies for the treatment of ACC have been conducted, and many more are ongoing or planned. Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine. These agents have shown modest clinical activity, although nonzero in the case of the immune checkpoint inhibitors. Clinical trials are ongoing to evaluate whether this clinical activity may be augmented through combinations with other immune-acting agents or targeted therapies.

Apatinib for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer: Results From a Randomized, Placebo-Controlled, Parallel-Arm, Phase II Trial

2013 ◽  
Vol 31 (26) ◽  
pp. 3219-3225 ◽  
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Jianming Xu ◽  
Weijian Guo ◽  
Jianping Xiong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Failure ◽  
Treatment Options ◽  
Metastatic Gastric Cancer ◽  
Daily Group ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Group B ◽  
Experienced Treatment

Purpose Patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy have no treatment options that clearly confer a survival benefit. This trial investigated the safety and efficacy of apatinib, an inhibitor of vascular endothelial growth factor receptor, as a treatment option for heavily pretreated patients with mGC. Patients and Methods Patients who experienced treatment failure with at least two chemotherapeutic regimens were randomly assigned to receive placebo (group A), apatinib 850 mg once daily (group B), or apatinib 425 mg twice daily (group C). Results We enrolled 144 patients onto this study. In groups A, B, and C, the median overall survival (OS) times were 2.50 months (95% CI, 1.87 to 3.70 months), 4.83 months (95% CI, 4.03 to 5.97 months), and 4.27 months (95% CI, 3.83 to 4.77 months), respectively, and the median progression-free survival (PFS) times were 1.40 months (95% CI, 1.20 to 1.83 months), 3.67 months (95% CI, 2.17 to 6.80 months), and 3.20 months (95% CI, 2.37 to 4.53 months), respectively. There were statistically significant differences between the apatinib and placebo groups for both PFS (P < .001) and OS (P < .001 and P = .0017). Nine patients had a partial response (three patients in group B and six patients in group C). Toxicities were tolerable or could be clinically managed. The most common grade 3 to 4 adverse events were hand-foot syndrome and hypertension. Hematologic toxicities were moderate, and grade 3 to 4 hematologic toxicities were rare. Conclusion Apatinib showed improved PFS and OS in heavily pretreated patients with mGC who had experienced treatment failure with two or more chemotherapy regimens.

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