Gastric cancer after nivolumab and FLOT – what experimental options are available?
In gastric cancer, if the patient has previously received FLOT chemotherapy and nivolumab immunotherapy, the subsequent treatment strategy and experimental options are decisively determined by the molecular profile (HER2, Claudin 18.2, MSI/MMR status) and the exact context of prior therapy. Based on available data, standard options and those investigated in clinical trials include the combination of anti-angiogenic therapy with chemotherapy (for example, ramucirumab plus taxane-based treatment, which is also being studied following nivolumab), as well as molecularly targeted agents. For Claudin 18.2-positive tumours, targeted therapy (e.g., zolbetuximab with chemotherapy), whereas in HER2-positive cases, antibody-drug conjugates (e.g., trastuzumab deruxtecan) and other bispecific or targeted agents represent an important avenue. In addition, alternative immuno-oncology approaches, such as bispecific antibodies (such as the PD-1/CTLA-4 inhibitor cadonilimab) or dual immune checkpoint blockade, are also being investigated.
In the event of progression following prior chemotherapy and immunotherapy, the use of anti-angiogenic agents, such as ramucirumab in combination with a taxane, is a relevant treatment modality in advanced gastric cancer.
In the presence of molecular targets, therapy can be restructured following resistance: in the case of CLDN18.2 expression, zolbetuximab-based treatments emerge, while in HER2-positive cases, advanced antibody-drug conjugates and bispecific antibodies are considered in clinical trials.
References
- Efficacy and safety of taxane plus ramucirumab for advanced gastric cancer after chemotherapy plus nivolumab doi:10.1016/S0140-6736(23)00620-7
- Zolbetuximab combined with chemotherapy in a patient with CLDN18.2-positive advanced gastric cancer undergoing hemodialysis: a case report. PMID 42205758
- Gastric Carcinoma: Diagnosis, Staging, and Treatment. PMID 41084753
- Efficacy and safety of cadonilimab combined with chemotherapy for gastric or gastroesophageal junction adenocarcinoma: a single-arm meta-analysis. PMID 41789078
- Clinical advances and challenges of anti-angiogenic targeted therapy in gastric cancer. PMID 41211418
- A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer NCT03505320