Improved efficacy to cytotoxic agents chemotherapy after immune checkpoint inhibitors exposure in metastatic gastric cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 297-297
Author(s):  
Tamotsu Sagawa ◽  
Yasushi Sato ◽  
Kyoko Hamaguchi ◽  
Masahiro Hirakawa ◽  
Hiroyuki Nagashima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Characteristics ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Chemotherapy Response ◽  
Period Range ◽  
Ecog Ps

297 Background: An association between improved responses to chemotherapy after exposure to vaccine-based immunotherapy has been previously reported in other cancers. However, it is unclear whether the chemotherapy response improves after exposure to immunotherapy, such as immune checkpoint inhibitors (ICIs). The objective of this retrospective study was to evaluate whether chemotherapy (4th-line) would yield improved efficacy when given after exposure to anti-PD-1 antibody in metastatic gastric cancer (mGC). Methods: We investigated retrospectively clinical characteristics at baseline of mGC patients who received chemotherapy after progression of anti-PD-1 antibody (Nivolumab) between February 2018 and July 2019. Anti-PD-1 antibody was adapted as third-line therapy. Inclusion criteria for the analysis reported herein: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received chemotherapy including 5-fluoropyrimidines (5-FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, DCR by RECIST version 1.1, PFS, and OS. Results: Out of 27 treated with anti-PD-1 antibody, 10 patients were evaluable for responses and eligible to be included in this analysis. Patient characteristics were as follows: median age (range), 72 (50-88) years; male/female, 8/2; ECOG PS (0/1/2), 4/5/1; HER2 (+/-), 5/5; histology (differentiated/undifferentiated), 5/5; metastatic lesions (LN/peritoneum/liver/lung), 5/3/1/3; number of metastatic sites (1/≥2), 5/5; number of prior CTx regimens (3/4/5), 10/0/0; median period (range) from first line CTx, 18.8 (7.9-47.1) months; and CTx regimens (CPT-11/PTX/S-1+Oxaliplatin), 7/2/1; Among the 10 patients, 1 achieved a partial response, giving an ORR of 10.0%. Six patients had stable disease and three had progressive disease. The DCR was 70%. Median PFS and OS were 5.5M and 8.5M, respectively. These were no new irAEs appeared during CTx. Conclusions: In mGC patients, our study demonstrated that increased efficacy to cytotoxic agents chemotherapy given after exposure to ICI was higher as compared to our historical data from the pre-anti-PD1 era. Updated results will be presented.

Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 152-152
Author(s):  
Kyoko Kato ◽  
Yukiya Narita ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Her2 Positive ◽  
Period Range ◽  
Median Period ◽  
Metastatic Sites ◽  
Ecog Ps

152 Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.

scholarly journals Dramatic Response in a Patient with Metastatic Gastric Cancer Using Trifluridine/Tipiracil after Rapid Disease Progression while on Nivolumab

2020 ◽  
Vol 13 (3) ◽  
pp. 1381-1386
Author(s):  
Kazuki Nozawa ◽  
Yukiya Narita ◽  
Waki Hosoda ◽  
Kei Muro
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Pattern ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Laboratory Data ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Hyperprogressive Disease

The introduction of immune checkpoint inhibitors has redefined the treatment strategy and changed the way tumor assessments are made because of its response pattern. Studies have suggested that initiating chemotherapy after checkpoint inhibitors may have high anti-tumor activity in some cancer types. This response pattern has not been reported in patients with gastric cancer, and particularly for the combination of trifluridine/tipiracil. A 69-year-old man presented at follow-up for metastatic gastric cancer being treated with nivolumab, an anti-PD-1 antibody. Computed tomography of the liver showed a rapid 4-fold growth of the metastasis compared with baseline measurements taken while receiving paclitaxel and ramucirumab. It met the definition of a phenomenon called hyperprogressive disease. Nivolumab was discontinued, and he was switched to trifluridine/tipiracil. The liver metastasis was shrunk markedly after 2 months with improvement in his performance status and laboratory data. Sequential therapy starting with immune checkpoint inhibitors followed by cytotoxic agents such as trifluridine/tipiracil may have an apparent efficacy in gastric cancer even though prior immunotherapy demonstrates hyperprogressive disease.

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 Immune Checkpoint Inhibitors in Pre-Treated Gastric Cancer Patients: Results from a Literature-Based Meta-Analysis

2020 ◽  
Vol 21 (2) ◽  
pp. 448 ◽  
Author(s):  
Giandomenico Roviello ◽  
Silvia Paola Corona ◽  
Alberto D’Angelo ◽  
Pietro Rosellini ◽  
Stefania Nobili ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Metastatic Gastric Cancer ◽  
Control Group ◽  
Tumour Location

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64–1.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy.

scholarly journals Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000791 ◽  
Author(s):  
Byung Woog Kang ◽  
Ian Chau
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Metastatic Gastric Cancer ◽  
Scientific Data ◽  
Current Status

Immunotherapy is revolutionising cancer treatment and has already emerged as standard treatment for patients with recurrent or metastatic gastric cancer (GC). Recent research has been focused on identifying robust predictive biomarkers for GC treated with immune checkpoint inhibitors (ICIs). The expression of programmed cell death protein-ligand-1 (PD-L1) is considered a manifestation of immune response evasion, and several studies have already reported the potential of PD-L1 expression as a predictive parameter for various human malignancies. Meanwhile, based on comprehensive molecular characterisation of GC, testing for Epstein-Barr virus and microsatellite instability is a potential predictive biomarker. Culminating evidence suggests that novel biomarkers, such as the tumour mutational burden and gene expression signature, could indicate the success of treatment with ICIs. However, the exact roles of these biomarkers in GC treated with ICIs remain unclear. Therefore, this study reviews recent scientific data on current and emerging biomarkers for ICIs in GC, which have potential to improve treatment outcomes.

scholarly journals Case Report: Severe Immune-Related Cholestatic Hepatitis and Subsequent Pneumonia After Pembrolizumab Therapy in a Geriatic Patient With Metastic Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Yang ◽  
Chenfei Zhou ◽  
Fei Yuan ◽  
Liting Guo ◽  
Liu Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Obstructive Jaundice ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Gastric Cancer ◽  
Cholestatic Hepatitis ◽  
Symptom Improvement ◽  
Post Discharge ◽  
Clinical Benefits

Background: Immune checkpoint inhibitors have provided significant clinical benefits to many patients with advanced cancer; however, severe immune-related adverse events (irAEs) have occurred. Detecting and treating irAEs early could improve patient prognoses. Therefore, clinicians and patients should understand that these irAEs exist, especially those that are rare and serious.Case Presentation: In this report, an 86-year-old male patient, diagnosed with metastatic gastric cancer involving the peritoneum and retroperitoneal lymph nodes was treated with 5-cycle pembrolizumab therapy (100 mg q 2 weeks), achieving a partial response. However, the patient developed Grade 3 cholestatic hepatitis and delayed pneumonia 10 days and 2 months after the final pembrolizumab dose, respectively. After discontinuing the pembrolizumab therapy and excluding obstructive jaundice with imaging studies, the patient received steroid therapy, with a gradual symptom improvement. However, the patient developed delayed pneumonia with type 1 respiratory failure 1-month post-discharge. Several microbiologic tests were negative, and immune-associated pneumonia was suspected, but we could not exclude an opportunistic infection. The patient recovered with steroids and antibiotics and remained in partial remission 5 months after pembrolizumab withdrawal.Conclusions: Cholestatic hepatitis is a rarely reported toxicity of immune checkpoint inhibitors, which should be suspected and addressed once obstructive jaundice is ruled out. In addition, clinicians should be aware that irAEs can occur at any time in patients treated with immune checkpoint inhibitors and that a timely diagnosis should be made.

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals First-Line Chemotherapy Response Is a Predictive Factor for Immune Checkpoint Inhibitors Treatment in Advanced Urothelial Carcinoma, a Real World Retrospective Study

2021 ◽  
Author(s):  
Jian-Ri Li ◽  
Shian-Shiang Wang ◽  
Kevin Lu ◽  
Chuan-Shu Chen ◽  
Chen-Li Cheng ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
The Other ◽  
Chemotherapy Response ◽  
First Line ◽  
Advanced Urothelial Carcinoma ◽  
Line Chemotherapy

Abstract Background: Immune checkpoint inhibitors (ICIs) have become important tools for the treatment of advanced urothelial carcinoma (aUC). However, the clinical strategy using ICIs and chemotherapy is still controversy. The aim of this study was to evaluate the association of clinical parameters in aUC patients with ICIs treatment.Methods: We retrospectively analyzed aUC patients who received atezolizumab and pembrolizumab between January 2015 and October 2020. The associations between baseline demographics and clinical outcomes were evaluated.Results: Of the 74 included patients, the median age was 67 years. Among them, 53 patients received atezolizumab and the other 21 received pembrolizumab. There were 50 patients receiving first line ICIs therapy and the other 24 received second line monotherapy. Fifty-two (83.87%, 52/62) received cisplatin among all chemotherapy patients. The median progression free survival was 10.94 months and the overall survival was 28.44 months. Poor chemotherapy response or no chemotherapy, liver metastases, Eastern Cooperative Oncology Group (ECOG) status and higher neutrophil/lymphocyte ratio (NLR) were associated with higher risk of diseases progression (HR=5.70, 95% CI 2.04-15.90, p=0.001, HR=6.08, 95% CI 1.79-20.57, p=0.004; HR=5.40, 95% CI 1.76-16.57, p=0.003; HR=6.08, 95% CI 2.56-14.44, p<0.001 and HR= 1.02, 95% CI 1.01-1.03, P=0.002 respectively). Liver metastases and WBC before ICI were associated with increased death risk (HR=11.95, 95%CI 3.22-44.34, p<0.001; HR=1.0001, 95% CI 1.00001-1.00002, p=0.036 respectively) while ICI response was associated with decreased death (HR=0.22, 95%CI 0.08-0.62, p=0.004). Chemotherapy responders were associated with better ICI treatment response (OR=6.52, 95%CI 1.45-29.24, p=0.014) while lymph node metastases and poor ECOG was associated with poor ICI response (OR=0.31, 95%CI 0.10-0.94, p=0.038; OR=0.32, 95%CI 0.11-0.95, p=0.040).Conclusions: Our data showed predictive role of first-line chemotherapy response to ICIs treatment efficacy in aUC patients as well as other prognostic factors, such as ECOG status, serum white blood cell count or NLR and liver metastases.

scholarly journals Future Perspective of Chemotherapy and Pharmacotherapy in Thymic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5239
Author(s):  
Rui Kitadai ◽  
Yusuke Okuma
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thymic Carcinoma ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Cytotoxic Agents ◽  
Future Perspective ◽  
Driver Mutations ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Tumors

Thymic carcinoma is a rare cancer that arises from thymic epithelial cells. Its nature and pathology differ from that of benign thymoma, presenting a poorer prognosis. If surgically resectable, surgery alone or surgery followed by chemoradiotherapy or radiotherapy is recommended by the National Comprehensive Cancer Network Guidelines. Metastatic and refractory thymic carcinomas require systemic pharmacotherapy. Combined carboplatin and paclitaxel, and cisplatin and anthracycline-based regimens have been shown a fair response rate and survival to provide a de facto standard of care when compared with other drugs employed as first-line chemotherapy. Cytotoxic agents have been pivotal for treating thymic carcinoma, as little is known regarding its tumorigenesis. In addition, genetic alterations, including driver mutations, which play an important role in treatments, have not yet been discovered. However, molecular pathways and biomarker studies assessing thymic epithelial tumors have been reported recently, resulting in the development of new agents, such as molecular targeted agents and immune checkpoint inhibitors. As treatment options are currently limited and the prognosis remains poor in metastases and recurrent thymic carcinoma, genetic alterations need to be assessed. In the present review, we focused on the current role of targeted therapies and immune checkpoint inhibitors in treating thymic carcinoma.

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