Dr Enzinger on the Current Landscape of Biomarker-Driven Approaches in Esophageal Cancer

"In the future, our hope is…not only to expand…the ways in which we target HER2 and CLDN 18.2, but also to expand to other targets [like] FGFR, MET, EGFR…EpCAM and C-CAM.”

Peter C. Enzinger, MD, director of the Center for Esophageal and Gastric Cancer, institute physician, and a medical oncologist at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed currently available and emerging biomarker-driven approaches of interest in esophageal cancer.

Although chemotherapy remains a cornerstone, the treatment paradigm is increasingly defined by the identification of specific targets, most notably HER2 and Claudin 18.2 (CLDN18.2), Enzinger began. The advancement of CLDN18.2-directed therapy represents a significant shift for patients with HER2-negative disease, as evidenced by the October 2024 FDA approval of zolbetuximab (Vyloy) in combination with platinum- and fluoropyrimidine-containing chemotherapy for adult patients with untreated, locally advanced or metastatic, HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. This landmark decision was supported by findings from the phase 3 SPOTLIGHT trial (NCT03504397), which evaluated zolbetuximab with mFOLFOX6 (leucovorin, fluorouracil, and oxaliplatin), and the phase 3 GLOW trial (NCT03653507), which assessed the agent in combination with CAPOX (capecitabine [Xeloda] and oxaliplatin).

Although HER2-targeted agents such as trastuzumab (Herceptin) and fam-trastuzumab deruxtecan-nxki (Enhertu) have been vital components of care for over a decade, the approval of zolbetuximab marks the current threshold of targeted options, Enzinger stated. He asserted that the future of gastroesophageal therapy lies in refining existing targets and exploring new ones, such as FGFR, MET, EGFR, EpCAM, and C-CAM. Enzinger concluded that the goal for the field is to expand these biomarker-driven therapies as quickly and expansively as possible to improve patient outcomes.