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Influence of Taxanes on Treatment Sequence in Gastric Cancer
Sylvie Lorenzen1, Michael Stahl2, Ralf-Dieter Hofheinz3
1Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie, Klinikum rechts der Isar, Munich, Germany, sylvielorenzen@gmx.de.
Background:
Adenocarcinoma of the stomach and esophagogastric junction (EGJ) remains a tumor entity with a poor prognosis. While meaningful advances have been made in the treatment of other solid tumors in the past years, numerous phase III studies in gastric cancer have had negative outcomes. Successes of targeted therapies so far include the -introduction of trastuzumab in the first-line treatment of HER2-positive gastric cancer, and second-line anti-angiogenic treatment with the anti-VEGF-2 receptor antibody ramucirumab. Taxanes have become established in the perioperative setting and in second-line treatment and have set new standards. However, evidence for improved overall survival in the first-line treatment of advanced gastric cancer with taxanes is not convincing.
Methodology:
Expert consensus discussion on the scientific and clinical evidence for sequential systemic treatment for advanced gastric and EGJ cancer, taking into account data clinical outcomes from randomized controlled phase II and phase III trials.
Summary:
In first-line treatment of advanced gastric cancer, taxanes in combination with a platinum- and 5-fluorouracil-based regimen are generally not recommended because they lack a survival benefit and confer high toxicity. However, taxanes in first-line can be a treatment option for patients presenting with high tumor burden and strong pressure to achieve remission. Since the publication of several positive studies in second- and third-line therapy, sequential therapy is playing an increasingly important role in metastatic gastric and EGJ cancer. Key Message: Standard of care for the first-line treatment of gastric cancer is a platinum-fluoropyrimidine chemotherapy doublet combination. The standard of care after failure of platinum-based first-line therapy is ramucirumab in combination with paclitaxel. Data supporting this combination after previous taxane therapy are not yet available.
Insights
Standard first-line gastric cancer treatment involves platinum-fluoropyrimidine chemotherapy. While taxanes are not generally recommended first-line due to toxicity and lack of survival benefit, they may be considered for high tumor burden. Sequential therapy is crucial in advanced disease.
Area of Science:
- Medical Oncology
- Gastrointestinal Oncology
- Clinical Trials
Background:
- Gastric and esophagogastric junction (EGJ) adenocarcinoma presents a poor prognosis.
- Advances in other solid tumors contrast with negative outcomes in numerous gastric cancer phase III studies.
- Trastuzumab (HER2-positive) and ramucirumab (anti-angiogenic) represent successful targeted therapies.
Purpose of the Study:
- To provide an expert consensus on sequential systemic treatment for advanced gastric and EGJ cancer.
- To evaluate scientific and clinical evidence from randomized controlled trials.
Main Methods:
- Expert consensus discussion.
- Review of randomized controlled phase II and phase III clinical trial data.
Main Results:
- First-line taxane combinations with platinum-fluoropyrimidine are generally not recommended due to toxicity and lack of survival benefit.
- Taxanes may be considered in first-line for patients with high tumor burden requiring remission.
- Sequential therapy is increasingly important in metastatic gastric and EGJ cancer based on positive second- and third-line studies.
Conclusions:
- Standard first-line therapy for gastric cancer is a platinum-fluoropyrimidine chemotherapy doublet.
- Ramucirumab plus paclitaxel is the standard of care after first-line platinum-based therapy failure.
- Evidence for this combination after prior taxane therapy is currently unavailable.
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