Immunotherapy is an emerging approach to oncology treatment and has been a hot topic in recent years. With new breakthroughs in immunotherapy in lung cancer, melanoma, and some lymphomas, immunotherapy is also coming to gastric cancer, where immune checkpoint inhibitors have gained some indications for gastric cancer. So, which gastric cancers might immune drugs like immune checkpoint inhibitors work against?
What gastric cancers are immune checkpoint inhibitors used for?
The programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab are the fast-growing immune checkpoint inhibitors in gastric cancer.
Pabrolizumab is the first drug approved for immunotherapy in gastric cancer. in May 2017, the US Food and Drug Administration (FDA) accelerated approval of the tumor immunotherapy pabrolizumab for unresectable or metastatic tumors with highly microsatellite instable (MSI-H) or defective mismatch repair (dMMR) that have progressed after treatment and for which no alternative treatment options are available. solid tumors (including gastric cancer). This is the first FDA approval of a tumor immunotherapy drug that is not specific to a cancer type.
Subsequently, the FDA approved pablizumab for the treatment of patients with recurrent locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma who are positive for PD-L1, the ligand for PD-1.
The 2017 and 2018 National Comprehensive Cancer Network (NCCN) guidelines for gastric cancer have included immunotherapy, recommending pabrolizumab as a second-line or post-second-line treatment option for dMMR (defective mismatch repair)/MSI-H (high microsatellite instability) advanced gastric cancer; as a third-line or post-third-line treatment for PD-L1-expressing recurrent locally advanced or metastatic gastric cancer.
Navulizumab was approved in Japan in September 2017 for the treatment of unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy.
Only nabolutumab and pablizumab, among PD-1/PD-L1 inhibitors, are currently available in China but have not yet been approved for use in gastric cancer, and many are in clinical filings or clinical studies.
Efficacy prediction may lead to more precise selection of target patients
The main problem encountered with current immune checkpoint inhibitors is the relatively low overall remission rates in patients. Therefore, the search for biomarkers that meaningfully predict efficacy is something that needs to be explored in depth. Biomarkers being investigated by investigators include PD-L1 expression in tumor cells, CD8+ T cell density, and tumor cell mutational load. Finding appropriate biomarkers for efficacy prediction will facilitate more precise selection of populations for which immune checkpoint inhibitors are appropriate, thus allowing these gastric cancer patients to receive immunotherapy effectively.