Considering the Zanidatamab Triplet in the PD-L1 CPS <1 Patient

In this episode, Dr. Wainberg, Dr. Shameem, and Dr. Elimova discuss how HERIZON-GEA-01 data inform first-line decisions for patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) <1 disease. Dr. Wainberg poses the scenario of a patient with CPS <1 presenting to clinic after a hypothetical FDA approval of a zanidatamab-based regimen, and asks Dr. Shameem how he would approach doublet versus triplet therapy.

Dr. Shameem states that his decision would align with the FDA label. If the label supports the addition of immunotherapy to zanidatamab plus chemotherapy regardless of PD-L1 status, he would offer the triplet, citing the durable responses and the survival benefit seen in HERIZON-GEA-01. He notes that many patients never reach second-line therapy, so the first-line choice is often the best opportunity to deliver an active regimen. He describes this as a shared decision, acknowledging that immunotherapy is not devoid of side effects and that those side effects can be life-threatening.

Dr. Wainberg then asks Dr. Elimova, setting cost aside, whether she would use a tislelizumab-containing regimen in a United States CPS <1 patient, given that pembrolizumab is not approved in that subgroup. Dr. Elimova responds that she would be inclined to offer all three agents if approved and accessible, noting that 35% of patients in HERIZON-GEA-01 were PD-L1 negative by TAP score. She would still discuss KEYNOTE-811 and explain the discrepancy, but the data support offering the triplet. Dr. Wainberg adds that he, too, would likely offer the triplet, reasoning that immunotherapy does not benefit patients as much in later lines of therapy, and that a dataset showing a survival advantage is difficult to ignore.

In the next episode, “Managing Diarrhea and Other Adverse Events on Zanidatamab-Based Regimens,” Dr. Shameem and Dr. Elimova describe prophylaxis protocols and practical counseling for the diarrhea risk associated with zanidatamab.