Dr. Sonbol on Navigating Treatment Selection in Gastroesophageal Cancers

Mohamad (Bassam) Sonbol, MD, hematologist and oncologist, Mayo Clinic, assistant program director, Virtual Oncology Fellowship, Syrian American Medical Society, member, North American Neuroendocrine Tumor Society, discusses key considerations for treatment selection in patients with gastroesophageal junction (GEJ) cancers.

Genetic-based biomarker screening is a vital first step in selecting a treatment approach, Sonbol begins. Aside from broad next-generation sequencing (NGS), the 3 most important biomarkers to screen for in patients with locally advanced or metastatic GEJ adenocarcinomas are PD-L1, HER2, mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) status, he states. 

Patients with MSI-H adenocarcinomas may benefit most with the use of pembrolizumab (Keytruda) monotherapy, Sonbol states. However, many patients with this tumor type are microsatellite stable or MMR proficient, he notes. These patients should specifically be tested for HER2 positivity before administering treatment, as recent clinical data support the administration of pembrolizumab in combination with trastuzumab (Herceptin) and chemotherapy for patients with locally advanced unresectable or metastatic HER2-positive adenocarcinomas, Sonbol explains.

Conversely, patients with HER2-negative adenocarcinomas should then undergo PD-L1 testing, Sonbol continues. For those with a PD-L1 combined positive score (CPS) below 5%, patients should receive chemotherapy alone, while those with PD-L1 CPS of above 5% should receive treatment with nivolumab (Opdivo) in addition to chemotherapy, he says. Patients with squamous cell carcinomas should also undergo PD-L1 testing and MSI evaluation, Sonbol states. Pembrolizumab plus chemotherapy should be considered for those with PD-L1 CPS scores above 10%. The combination of nivolumab plus chemotherapy may also be considered for these patients, Sonbol adds. As with adenocarcinomas, PD-L1–negative patients with squamous cell carcinoma should receive chemotherapy alone, he reiterates.

Lastly, considering when to utilize dual checkpoint inhibitors in patients with GEJ cancers is always important, such as when to use them. Ultimately, dual checkpoint inhibitors are a favorable option for patients with gastroesophageal cancers who have significant contraindications for platinum-based chemotherapy, Sonbol emphasizes. For example, in patients with a severe neuropathy where platinum-based therapy is not an option, dual checkpoint inhibitors would be considered.