Prescribing Practices and Clinical Impact of Next Generation Sequencing in Routine Practice in Solid Tumors – Real World Experience in Lmic

Abstract Molecular characterization of disease is essential for precision medicine due to novel predictive biomarkers. Multiple next-generation sequencing (NGS) platforms are available, but their expense and clinical utility vary. Even if a targetable mutation is detected, corresponding drugs may not be available or affordable. No prior studies in Pakistan have focused on integrating NGS results into patient care to assist with therapeutic decision-making and survival outcomes. This retrospective study aimed to evaluate the molecular profiling and therapeutic implications of NGS testing across solid tumors. It included all patients with histologically proven malignancy (metastatic or non-metastatic) who had NGS analysis at Aga Khan University Hospital (AKUH) from June 1, 2020, to June 1, 2023. Foundation One was the NGS platform used. From 2020 to 2023, 192 patients underwent NGS. The majority were male (55.2%) and aged over 50 years (71.9%). The most common indications for NGS were carcinoma of unknown primary (CUP) and lung cancers, representing 26% and 25% respectively, followed by colon (9%) and breast cancers (8%). Most patients had metastatic disease (98.4%). Common mutations in lung cancer were EGFR (16.3%) and KRAS G12C (14.3%). In unknown primary, breast, and colon cancers, the most common mutations were BRAF (8%), PIK3CA (18%), and KRAS (42.1%), respectively. Microsatellite instability (MSI) testing was performed in 95% of patients, with 6% being MSI high. Actionable alterations were detected in 31.8% of patients, but only 17.2% received genotype-matched treatment, mostly as a first-line treatment for lung cancer. The primary barriers were drug availability and affordability. Our results show that the implementation of NGS analysis supports clinical decision making. However, these results were applicable to a small percentage of patients. For better compliance and applicability, drug availability and cost of treatment needs to be addressed