ASCO Guideline Update zum gastroösophagealen Karzinom – medonline.at
The American Society of Clinical Oncology (ASCO) updated its clinical practice guidelines for gastroesophageal carcinoma to prioritize biomarker-driven therapies. The updates emphasize the use of immunotherapy and targeted agents for patients with specific genetic markers, such as PD-L1 and HER2, to improve survival rates in metastatic and locally advanced cases, according to the ASCO guidelines reported by medonline.at.
These guidelines refine the treatment sequence for esophageal and gastroesophageal junction (GEJ) cancers. They move away from a uniform chemotherapy approach toward personalized medicine based on the molecular profile of the tumor.
How does immunotherapy change first-line treatment?
Immunotherapy is now a cornerstone of first-line treatment for metastatic gastroesophageal cancer, provided the patient’s tumor expresses certain biomarkers. According to ASCO, the combination of nivolumab and chemotherapy is recommended for patients whose tumors show a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of 5 or higher.
This shift marks a departure from previous standards that relied almost exclusively on platinum-based chemotherapy. Doctors now use the CPS score to determine if a patient will likely respond to immune checkpoint inhibitors.
For patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), the guidelines suggest immunotherapy as a primary option regardless of PD-L1 status. These specific genetic traits make the cancer more visible to the immune system, increasing the effectiveness of drugs like pembrolizumab.
What is the role of HER2 testing in these guidelines?
HER2 testing is mandatory for all patients with adenocarcinoma of the esophagus or GEJ. ASCO guidelines state that patients with HER2-positive tumors should receive trastuzumab in combination with chemotherapy.
The guidelines specify that this targeted approach is more effective than chemotherapy alone for this specific subset of patients. If a tumor is HER2-negative, trastuzumab is omitted to avoid unnecessary toxicity and cost.
This biomarker-led strategy creates a clear divide in treatment paths. One path leads to HER2-targeted therapy, while the other leads to immunotherapy or standard chemotherapy based on PD-L1 and MSI status.
How are locally advanced tumors managed?
For locally advanced gastroesophageal carcinomas, the guidelines continue to support neoadjuvant chemoradiotherapy followed by surgical resection. This approach is based on the established CROSS trial data, which showed improved overall survival compared to surgery alone.
The updated guidance emphasizes the importance of a multidisciplinary team. Surgeons, oncologists, and radiologists must coordinate the timing between the completion of radiation and the start of surgery to maximize the chance of complete tumor removal.
In cases where surgery is not feasible, the guidelines suggest continuing with definitive chemoradiotherapy or transitioning to systemic therapies based on the tumor’s molecular markers.
How do these updates differ from previous standards?
The most significant change is the transition from histology-based treatment to biomarker-based treatment. Previously, the primary decision point was whether the cancer was squamous cell carcinoma or adenocarcinoma.
While histology still matters, the ASCO guidelines now place higher weight on PD-L1, HER2, and MSI-H status. This allows for a more granular approach to care.
Comparing the old and new frameworks reveals a tighter integration of precision medicine. The previous standard often applied the same chemotherapy regimen to all adenocarcinoma patients. The current guidelines split these patients into three distinct groups: HER2-positive, PD-L1-positive, and those who do not meet either criteria.
This stratification aims to reduce the number of patients receiving ineffective treatments. By matching the drug to the mutation, clinicians can target the specific drivers of the tumor’s growth.
What remains uncertain in gastroesophageal care?
Despite these updates, the optimal sequence of immunotherapy remains a point of study. ASCO notes that more data is needed to determine if immunotherapy should be used before or after certain types of chemotherapy in all patient populations.
There is also ongoing research into the use of immunotherapy in the perioperative setting. While it shows promise in early trials, it has not yet replaced the standard neoadjuvant chemoradiotherapy for all patients.
The guidelines suggest that clinicians monitor emerging data on novel targeted agents for patients who do not respond to current first-line therapies.