423P - Insights into clinically actionable biomarkers in an Indian cancer cohort of 1000 patients using comprehensive genomic profiling (CGP)

Background

CGP through Next-Generation Sequencing (NGS) detects a broad spectrum of therapeutic, prognostic, and predictive biomarkers - tumor mutational burden (TMB), microsatellite instability (MSI) burden, somatic BRCA (sBRCA), and homologous recombination repair genes (HRR) providing a more cost-efficient and tissue-preserving approach than serial single-biomarker analysis.

Methods

1000 biopsy proven cancer patients at HCG cancer centre, were profiled using Illumina TruSight Oncology 500 (TSO500) assay on a NextSeq2000 in an IRB-approved study. The NGS findings were discussed in the molecular tumor board (MTB) and recommendations were documented.

Results

A total of 1735 genomic alterations were detected (≥1mutations/sample). CGP identified genetic alterations with therapeutic and prognostic implications in 80% of patients (Tier I- 44%, Tier II-54%, Tier III-14%) . CGP revealed a higher number of druggable genes (48%) than small panels (14%). TMB and MSI-H were observed in 15% and 1% of the cohort respectively, started on IO and are on follow-up. HRR pathway alterations including sBRCA were detected in 15% of cohort, initiated on platinum or PARP inhibitors and achieved a complete pathological response . Other significant alterations detected were EGFR, KRAS/ BRAF, PIK3CA, cKIT, PDGFRA, ARID1A, ARID2, and FGFR, NTRK. RNA sequencing yielded 64 RNA alterations (48 translocations and 16 splice variants). Androgen receptor splice variants were observed in >35% of prostate carcinoma patients for whom androgen inhibitors were discontinued and taxane therapy was initiated. Other frequent fusions detected were: TMPRSS-ERG, RPS6KB1-VMP1, EML4-ALK, NTRK, PDGFRA and EWSR. CGP also revealed many resistance mechanism genes across cancer spectrum which enabled change in 2nd/3rd-line therapy. Table: 423P

Clinical management of the main cancer types informed by actionable biomarkers detected by CGP

Conclusions

CGP identified more druggable gene aberrations across diverse cancers enabling optimizing personalized cancer treatment in Indian patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B.S. Ajaikumar: Financial Interests, Institutional, Member of Board of Directors, Executive Chairman: HCG. All other authors have declared no conflicts of interest.