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Cancer Res. 2017 Jul 1;77(13):3666-3671. doi: 10.1158/0008-5472.CAN-16-3338. Epub 2017 Apr 26.

Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
2
INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. chanocks@mail.nih.gov.

Abstract

Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic datasets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that exceed a proposed threshold for response to checkpoint inhibitors. Overall, 8.9% of cases displayed profiles that could benefit from combination therapy, which corresponded to approximately 11.2% of U.S. annual incident cancer cases. Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS, and PTEN We also noted a high burden of NsM in cases with targetable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2, and MET Our results indicate that a significant proportion of solid tumor patients are eligible for immuno-targeted combination therapy, and they suggest prioritizing specific cancers for trials of certain targeted and checkpoint inhibitor drugs. Cancer Res; 77(13); 3666-71. ©2017 AACR.

PMID:
28446466
PMCID:
PMC5522610
DOI:
10.1158/0008-5472.CAN-16-3338
[Indexed for MEDLINE]
Free PMC Article

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