Biomarker Testing and Unmet Needs in Gastric/GEJ Cancers

Geoffrey Y. Ku, MD, discusses the current state of biomarker testing in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma, and why the field is still far from delivering a personalized treatment for every patient. According to Ku, 4 biomarkers are now considered standard of care in the metastatic setting: HER2, mismatch repair (MMR) status, PD-L1 expression, and claudin 18.2.

Ku frames the current landscape against a clear long-term goal. The field will only arrive, he says, when there is truly a personalized treatment for everyone and the vast majority of patients are cured. While he acknowledges substantial progress over the last 15 years, he notes that the field remains "nowhere close" to that goal.

Walking through the current testing paradigm, Ku points to HER2 as the longest-standing biomarker in gastric/GEJ cancers, established in this setting in 2010. MMR testing identifies patients with MSI tumors, PD-L1 expression helps determine the role of immunotherapy, and claudin 18.2 is the most recent addition to the list. In totality, Ku says, patients should be tested for all 4, because these results open up the role of immunotherapy as well as targeted therapies using anti-HER2 or anti-claudin 18.2 strategies.

Ku describes this as a significant shift from the era before 2010, when there were literally no biomarkers in this disease. At the same time, he points out that many patients still do not have any of these biomarkers and are therefore eligible to receive chemotherapy alone.

Looking ahead, Ku identifies several ongoing unmet needs in the treatment of gastroesophageal cancer. The first is target discovery, meaning the identification of additional novel targets. The second is refining immunotherapy so that both PD-L1–positive and PD-L1–negative tumors benefit. The third is identifying more robust biomarkers for immunotherapy.

Click for more insight from Ku, including his thoughts on CAR-T cell therapy, bispecific antibodies, and perioperative therapy in patients with gastric/GEJ cancers.