Molecular insights from comprehensive genomic profiling data in advanced metastatic colorectal cancer in South Asian population: A retrospective observational study
Authors: Fathima Nusrath , Verma Krithika , Subramanyam Paridhy V. , Mukherjee Nilesh , Tanwar Nishtha , Jayaraman Sharanya , Rangan Saranya , Mahanti Shreya , Saha Prabir , Javle Vyomesh , Khuntia Satya P. , Santani Harshi , Ashwini P , Peddagangannagari Sreekanth R. , Gowda Pooja , Varghese Linu , Gore Adwaita , Patel Amol , Sainani Anjana , Karpe Ashay , Avinash C. B. , Patodiya Bharat , Biswas Ghanashyam , Lokeshwar Nilesh , Ranade Rohit R. , Rajpurohit Sajjan , Juat Necy S. , Tagarda Federico Miguel R. , Cornel-Ong Annielyn , Teh Catherine , Gangadharan V. P. , Jain Amit , Sumon Mostafa A. , Deshpande Ramakant , Patil Vijay , Sathyanarayanan Vishwanath , Suresh A.V.S. , Chugh Bhuvan , Zawar Abhinav , Gupta Ajay , Shah Akshay , Punia Ankur , Rumman Kamruzumman , Kamath Mangesh , Raghuram Saadvik , Vivek Sai , Shrestha Sudip , Gupta Vineet G. , Pramanik Raja , Bhosale Bharat , Kothari Rushabh , Warrier Arun R. , Guhan P. , Lavingia Viraj , Sarathy Vinu , Mishra Sourav K. , Thirumalairaj Raja , Nayak Sandeep , Rishi Kshitij D. , Goswami Hitesh M. , Veldore Vidya H. 
Published: June 2024

Background:

An increase in colorectal cancer incidence has been reported in India, often presenting in advanced stages and resulting in poor survival. However, the genomic and therapeutic landscape is not well understood.

Objective:

The primary objective of the study was to understand the mutational profile of metastatic colorectal cancer in the Southeast Asian cohort, and the secondary objective was to define the proportion of patients with therapeutically significant variants.

Materials and Methods:

This retrospective study was conducted between January 2021 and September 2023, at 4baseCare Onco Solutions Pvt. Ltd., Bengaluru, Karnataka, India. Comprehensive genomic profiling (CGP) and biomarker testing for MSI, TMB, and PD-L1 was carried out in 477 metastatic advanced (Stage III/IV) colorectal cancer patients, for the current retrospective-observational study.

Results:

With CGP, we identified drivers/clinically actionable variants in 78.6% of the cohort (375 patients). Although 30.8% of our cohort (147 patients) was eligible to available targeted therapy, 29.5% (141 patients) were found to harbor variants imparting therapeutic resistance. The combined mutation frequency of APC, TP53, and KRAS was >50%, while KRAS constituted >90% of all RAS mutations. The mismatch repair (MMR) genes including MLH1, MLH3, MSH3, and POLE were exclusively found in colon cancers. Genomic alterations in several genes of prognostic/therapeutic significance were seen (mutations in PIK3CA, SMAD4, BRAF, and amplifications in KRAS, EGFR, and ERBB2). Of those tested, 15.8% (41 patients) of the cohort had high tumor mutation burden (TMB-H), 14% had high microsatellite instability (MSI-H) (46 patients), and 26.8% were programmed death-ligand 1 (PD-L1) positive (30 patients).

Conclusion:

Our study shows that CGP is an advantageous option for identifying subsets of patients eligible for various targeted therapies, thus, improving patient outcomes.