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.

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Mohamad Bassam Sonbol, MD, discusses key considerations for treatment selection in patients with gastroesophageal junction cancers.

Dr. Sonbol on Navigating Treatment Selection in Gastroesophageal Cancers  

Bassam Sonbol, MD, an oncologist at Mayo Clinic Arizona, discusses the role of pembrolizumab (Keytruda) in the treatment of patients with gastric cancer.

The role of the agent in the treatment of patients with gastric cancer has been examined over the last few years, according to Sonbol. Initially, use of pembrolizumab was limited to the third-line setting, but recently, the 

FDA’s Oncologic Drugs Advisory Committee voted against maintaining the accelerated approval of the agent

 for the treatment of patients with PD-L1–positive, recurrent or advanced gastric or gastroesophageal junction adenocarcinoma who have received 2 or more lines of therapy, Sonbol says. 

In the frontline setting, pembrolizumab was also examined with or without chemotherapy vs chemotherapy alone in the phase 3 KEYNOTE-062 trial (NCT02494583), Sonbol notes. Overall, the study yielded negative results. Although pembrolizumab monotherapy was non-inferior to chemotherapy, it was also not superior. As such, it is not often utilized as a monotherapy, especially in patients who are microsatellite stable, Sonbol concludes. 

Bassam Sonbol, MD, discusses the role of pembrolizumab in the treatment of patients with gastric cancer. 


Bassam Sonbol, MD

Articles

Dr. Sonbol on Navigating Treatment Selection in Gastroesophageal Cancers

Dr. Sonbol on the Role of Pembrolizumab in Gastric Cancer