Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management

Area of Science:

• Oncology
• Genomics
• Cancer Research

Background:

• The combination of immune checkpoint inhibitors and oncogene-targeted drugs offers potential for improved cancer management.
• However, the combined therapeutic potential of these agents has been underexplored.

Purpose of the Study:

• To estimate the proportion of cancer cases that could benefit from combined immunotherapy and targeted therapy.
• To analyze cancer genomic profiles for mutations amenable to current targeted agents or immunotherapy.

Main Methods:

• A survey of 13,349 public cancer genomic profiles was conducted.
• Cases were assessed for specific targetable mutations and a high burden of exome-wide nonsynonymous mutations (NsM).
• The threshold for NsM response to checkpoint inhibitors was considered.

Main Results:

• 8.9% of surveyed cases exhibited profiles suitable for combination therapy.
• This proportion represents approximately 11.2% of U.S. annual incident cancer cases.
• Frequently identified targetable mutations include PIK3CA, BRAF, NF1, NRAS, and PTEN. High NsM burden was noted with mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2, and MET.

Conclusions:

• A significant fraction of solid tumor patients may be eligible for immuno-targeted combination therapy.
• The findings support prioritizing specific cancers for clinical trials involving targeted drugs and checkpoint inhibitors.
• This research highlights the potential of personalized medicine in oncology.