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Geoffrey Ku, MD, Discusses New Non-Immunotherapy Targets and Therapies in GI Cancer
At the virtual Great Debates & Updates in Gastrointestinal (GI) Malignancies, Geoffrey Ku, MD, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, provided an overview of new non-immunotherapy targets and drugs in the GI cancer space.
Novel non-immunotherapy targets being pursued and actively evaluated include HER2, VEGF, CLDN18, and FGFR2.
In the setting of HER2-positive advanced gastric or gastro-esophageal junction cancers, trastuzumab plus chemotherapy remains the standard for first-line therapy; however, Dr Ku hinted at the possibility of trastuzumab deruxtecan soon being approved for use in the third-line setting for treatment of HER2-positive gastric cancer, based on promising data from a phase 3 study by Shitara et al.
Furthermore, new agents being explored in the anti-HER2 setting include ZW25 and PRS-343, which are being examined in ongoing phase 2 and phase 1/1b studies, respectively.
To date, studies have shown that VEGFR TKIs, including ramucirumab, apartinib, and regorafenib have modest activity for VEGF pathway inhibition when administered in the second-line setting or higher. These TKIs have also shown potential for synergistic activity when given in combination with anti-PD-1 antibodies.
According to Dr Ku, phase 3 trials of VEGFR TKIs combined with immunotherapy are pending, and may yield new treatment options for patients in this setting.
CLDN 18.2 and FGFR2 are novel targets for which the therapies zolbetuximab and bemarituzumab, respectively, have shown promise. These agents are currently being evaluated in phase 3 clinical trials, including the SPOTLIGHT study of 5-FU plus leucovorin and oxaliplatin (FOLFOX) with or without zolbetuximab and the FIGHT study of first-line FOLFOX with or without bemarituzumab.—Hina Porcelli
Ku G. Novel Non-Immunotherapy Targets And Agents in Gastroesophageal Cancer. Presented at: Great Debates & Updates in Gastrointestinal Malignancies; August 14-15, 2020; virtual.
