Molecularly targeted therapies in unresectable-metastatic gastric cancer. A systematic review

2011 ◽  
Vol 37 (8) ◽  
pp. 599-610 ◽  
Author(s):  
Flora Zagouri ◽  
Christos A. Papadimitriou ◽  
Meletios-Athanassios Dimopoulos ◽  
Dimitrios Pectasides
2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis

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.


2018 ◽  
Vol 07 (02) ◽  
Author(s):  
Ismail Essadi ◽  
Khalid Sair ◽  
Issam Lalya ◽  
Elomrani Abderrahim ◽  
Mouna Khouchani ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Brianna Lauren ◽  
Sassan Ostvar ◽  
Elisabeth Silver ◽  
Myles Ingram ◽  
Aaron Oh ◽  
...  

Background. The 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). The aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment. Methods. We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. The primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. Results. The most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. The only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/QALY. Conclusion. Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.


2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15527-e15527
Author(s):  
Wing-lok Chan ◽  
Kwok-keung Yuen ◽  
Steven Wai-kwan Siu ◽  
Ka-On Lam ◽  
Dora Lai Wan Kwong

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5934
Author(s):  
Romy M. van Amelsfoort ◽  
Karen van der Sluis ◽  
Winnie Schats ◽  
Edwin P. M. Jansen ◽  
Johanna W. van Sandick ◽  
...  

Background: Current treatment strategies have been designed to improve survival in locally advanced gastric cancer patients. Besides its impact on survival, treatment also affects health-related quality of life (HRQOL), but an overview of reported studies is currently lacking. The aim of this systematic review was therefore to determine the short- and long-term impact of chemotherapy, surgery, and (chemo)radiotherapy on HRQOL in locally advanced, non-metastatic gastric cancer patients. Methods: A systematic review was performed including studies published between January 2000 and February 2021. We extracted studies published in Medline, Embase, and Scopus databases that assessed HRQOL in patients with locally advanced, non-metastatic gastric cancer treated with curative intent. Studies using non-validated HRQOL questionnaires were excluded. Short-term and long-term HRQOL were defined as HRQOL scores within and beyond 6 months after treatment, respectively. Results: Initially, we identified 8705 articles (4037 of which were duplicates, i.e., 46%) and ultimately included 10 articles. Most studies reported that short-term HRQOL worsened in the follow-up period from 6 weeks to 3 months after surgery. However, recovery of HRQOL to preoperative levels occurred after 6 months. After completion of chemoradiotherapy, the same pattern was seen with worse HRQOL after treatment and a recovery of HRQOL after 6–12 months. Conclusions: In patients with locally advanced, non-metastatic gastric cancer, HRQOL deteriorated during the first 3 months after surgery and chemoradiotherapy. However, the long-term data showed a recovery of HRQOL after 6–12 months. To implement HRQOL in clinical decision making in current clinical practice, more research is needed.


Gut and Liver ◽  
2012 ◽  
Vol 6 (3) ◽  
pp. 388-394 ◽  
Author(s):  
Mi-Young Kim ◽  
Hwoon-Yong Jung ◽  
Kee Don Choi ◽  
Ho June Song ◽  
Jeong Hoon Lee ◽  
...  

2020 ◽  
Vol 16 (2) ◽  
pp. 4409-4418 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
Maria Massucci ◽  
...  

Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.


2015 ◽  
Vol 112 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Rahul Gadde ◽  
Leonardo Tamariz ◽  
Mena Hanna ◽  
Eli Avisar ◽  
Alan Livingstone ◽  
...  

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