Landscape of combination immunotherapy and targeted therapy to improve cancer management

Landscape of combination immunotherapy and targeted therapy to improve cancer management
Targeted drugs aim to inhibit molecular pathways that are crucial for tumour growth and maintenance. Immunotherapy endeavours to stimulate a host immune response. Combining these strategies might be more effective and improve clinical outcomes.
Over 13,000 somatic profiles of adult patients were analyzed to identify targetable mutations according to the NCI-MATCH list. Theoretical response to checkpoint inhibitors is based on available exomewide non-synonymous mutations counts, which can vary by tumor and stage.
In this study, 8.9% of cases from 17 tumor types, displayed profiles that could benefit from combination therapy. Frequently targetable mutations identified were: PIK3CA, BRAF, NF1, NRAS, and PTEN. High burden of NsM (non-synonymous mutations)
were found in cases with targetable mutations in SMO, DDR2, FGFR1,
PTCH1, FGFR2, and MET.
Limitations of the study: the samples are limited by availability from the database. Also, the NSM as clinical relevant predictor to checkpoint inhibitors has not been validated. Whether the combination strategy will be clinically relevant remains unclear.
This study has shown that in adult solid tumors such as melanoma, lung adenocarcinoma and squamous-cell carcinoma, colon, bladder and gastric cancer the combination strategy of targeted therapy and checkpoint inhibitors is theoretically feasible in about 10% of the patients. If this is clinically relevant, remains unclear. Whether results would be applicable to pediatric solid tumors is unknown and further research is needed to predict efficacy of individualized regiments in pediatric cancer patients.