Increased NGS testing and real-world clinical usage of targeted therapy: All dressed up, nowhere to go.

Journal of Clinical Oncology(2024)

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e13758 Background: National and International recommendations mandate panel- based biomarker testing for all advanced cases of NSCLC. However, analogous to uptake of many other state of the art cancer management strategies, the uptake of NGS based testing and subsequent targeted therapy varies greatly across socio-demographic groups, explained by awareness and economic restraints. This study investigates the potential differences in uptake of NGS based testing and precision medicine in advanced NSCLC patients from India. Methods: This is a single center non-interventional study where retrospective review of patient data of biomarker driven advanced NSCLC patients was carried out. The records were recovered from electronic health records of the hospital. Single gene testing for EGFR and ALK are performed using Roche Cobas V2 and D5F3 Ventana systems respectively. A machine learning algorithm: Classification and Regression Tree (CART) was employed. Results: A total of 5894 patients of advanced NSCLC were identified. Of these 33% received NGS based biomarker testing at diagnosis. The proportion of patients who received NGS tests increased over calendar time from 2014-2023, with an average increment of 15.8% every year, and peak increase in 2022 of 51%. NGS based testing yielded a positive result in 80% cases with a median turnaround time of 18.2+/-3 days. NGS detected 10.2% cases more in EGFR, 3.2% cases less in ALK, 3.1% more in ROS1. Overall NGS was able to detect 37.8% extra cases of biomarker driven cases. Among the biomarker driven, uptake of targeted therapy was 65% for MET, 83% for ROS1, 52% for RET, 17.6% for ERBB2, 63% for BRAF V600E, 75% for EGFR and 79% for ALK at any given point in the disease. None of the G12C KRAS received selective treatment owing to drug unavailability in the country. Applying the CART model, targeted therapy was received by patients younger than 68 years of age, male gender, with ECOG status 0-2, and absence of brain metastases at diagnosis. Patients with brain metastases at diagnosis, females and those >69 years of age were less likely to opt for TKI(p<0.02*). Conclusions: This is the largest cohort from India reporting real world uptake of NGS based biomarker testing and targeted therapy. There is a clear disparity in terms of gender and age group, possibly attributable to social stigmata and taboos prevailing in rural parts of the country. Despite increased detection rates, access to targeted therapy is still a concern owing to inaccessibility to drugs/ lack of global clinical trials in India as well as lack of patient support programs/groups.
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