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Molecularly Targeted Therapies for Gastric Cancer. State of the Art
Rossella Reddavid1,2, Simona Dagatti1,2, Caterina Franco1,2
1Department of Oncology, Università degli Studi di Torino, 10126 Torino, Italy.
Abstract:
Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents were approved by the FDA. We examined the efficacy and safety of novel drugs recently investigated. PubMed, Embase and Cochrane Library were searched for phase III randomized controlled trials published from January 2016 to December 2020. Patients in the experimental arm received molecular therapy with or without conventional chemotherapy, while those in the control arm had conventional chemotherapy alone. The primary outcomes were overall and progression-free survival. The secondary outcomes were the rate of tumor response, severe adverse effects, and quality of life. Eight studies with a total of 4223 enrolled patients were included. The overall and progression-free survival of molecular and conventional therapy were comparable. Most of these trials did not find a significant difference in tumor response rate and in the number of severe adverse effects and related deaths between the experimental and control arms. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.
Insights
Novel molecular therapies show unclear survival benefits for advanced gastric cancer patients. Inaccurate patient selection, especially for oncogene amplification, limits treatment efficacy.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Advanced and metastatic gastric cancer treatment has seen limited success with molecular therapies added to chemotherapy.
- Only three molecular agents have received FDA approval for gastric cancer.
- Phase III trials often fail to demonstrate significant survival benefits.
Purpose of the Study:
- To evaluate the efficacy and safety of recently investigated novel molecular drugs in advanced and metastatic gastric cancer.
- To analyze overall survival, progression-free survival, tumor response rates, and adverse events.
- To identify factors contributing to treatment outcomes.
Main Methods:
- Systematic review and meta-analysis of phase III randomized controlled trials.
- Searched PubMed, Embase, and Cochrane Library for trials published between January 2016 and December 2020.
- Included studies comparing molecular therapy (with or without chemotherapy) versus chemotherapy alone.
Main Results:
- Eight trials with 4223 patients were included.
- Overall and progression-free survival rates were comparable between molecular therapy and conventional chemotherapy arms.
- No significant differences were observed in tumor response rates or severe adverse effects.
Conclusions:
- Current molecular therapies offer unclear survival benefits for advanced and metastatic gastric cancer.
- Inaccurate patient selection, particularly regarding oncogene amplification and copy number, is a major limitation.
- Further research is needed to optimize patient selection for molecular therapies.
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