Discovery of Actionable Mutations through Comprehensive Genomic Profiling for Advanced Cancers in India

Comprehensive genomic profiling (CGP) assays help identify actionable mutations that can be targeted with drugs. We aimed to study the proportion of patients who have actionable mutations after undergoing CGP.

We conducted a multicenter, retrospective cohort study on adult patients with advanced nonhematologic malignancies who underwent CGP. We excluded reports which found common mutations detectable through focused testing, such as EGFR, ALK, ROS1 in lung cancer; HER2 in gastric, esophageal, and breast cancers and KIT in GIST (exclusion criteria). Genomic alterations were checked against the OncoKB database to categorise mutations into various levels based on actionability. Level 1: FDA-approved drugs for specific mutations and cancers; Level 2: expert-recommended FDA-approved drugs for the cancer type; Level 3: clinical evidence for benefit with a drug where neither the biomarker nor the drug is standard of care; Level 4: biological evidence for benefit with a drug where neither the biomarker nor the drug is standard of care.

We analysed NGS reports from 112 patients meeting our criteria. CGP revealed actionable mutations in 41% (46/112) of cases. Notably, 15% (7/46) of these actionable mutations held a level 1 recommendation indicating high clinical relevance. Among the remaining actionable mutations, 17% had a level 3 recommendation, while 67% were classified as level 4. The vast majority of drugs in level 4 were inaccessible in India or were still undergoing clinical trial testing. Of the patients who underwent CGP, when common mutations or targets were excluded, 6% of patients had level 1 alteration (7/112).

CGP in India identified actionable mutations in 41% of advanced cancer cases, highlighting its potential to offer personalised treatment opportunities beyond standard care. However, only 6% of patients who undergo CGP have a level 1 actionability.