We retrospectively analyzed 15,474 Japanese patients with solid tumors who underwent comprehensive genomic profiling (CGP) and received cytotoxic chemotherapy. Gene mutations and response were assessed across five chemotherapy classes: platinum-based, alkylating agents, antimetabolites, microtubule inhibitors, and topoisomerase inhibitors.
Genomic alteration data alone did not surpass organ-based models in predicting response. For platinum-based agents, the gene-only model had an AUC of 0.575 versus 0.604 for the organ-only model. A combined gene-organ model yielded an AUC of 0.618 (P < 0.01).Certain gene-organ interactions were associated with improved outcomes. For example, APC-mutated colorectal cancer showed higher ORR and prolonged TNT (hazard ratio, 0.82; 95% CI, 0.73–0.92; P < 0.001) for platinum-based drugs.
We suggeted incorporating both may improve exploratory predictions of chemotherapy response. These exploratory findings require prospective validation before any clinical application.