Experience of personalizing cancer treatment in economically-constrained and resource-restricted community oncology practice in India through cost-effective broad spectrum NGS and survival outcomes: An observational study of 3 years.

Abstract

e15173 Background: NGS based mutational findings are increasingly used in oncology practice to personalize treatment strategies. We elucidate the impact of comprehensive genomic profiling and the new avenues it opens for personalized precision medicine. Methods: This was a retrospective study evaluating patients who underwent a cost-effective (<US $1000), inhouse developed comprehensive NGS test. Descriptive data was tabulated & mutational distribution, therapeutic strategies and survival outcomes were evaluated. Results: A total of 336 patients were evaluated from a community oncology practice over the last 3 years in Western India. The mean age was 59.2 years; with F:M being 1.04:1 and stage distribution being 3.5%, 5.9%, 9.5% and 80.9% for Stage I, II, III and IV respectively. Comprehensive NGS was performed to evaluate SNVs, CNVs, and indels spanning across over 15000 loci for 1080 tumor specific genes wherein 71.7% were tissue-based, 24.4% were liquid biopsy-based and 3.8% were combined tissue-DNA and ctDNA-based analysis. Majority (69.9%) of the patients were pre-treated while 30% were therapy naïve. The most common cancers evaluated were Lung (18.1%), Pancreatobiliary (15.1%), Breast (11.3%), Gynaec (9.5%), and Lower GI (9.5%). Pathogenic mutations were reported in 83.6% of the cohort while in 16.3% no mutations were detected. Most common mutations observed in this retrospective study were TP53 (38.3%), KRAS (16.6%), PIK3CA (9.5%), EGFR (7.4%) and PTEN (5.6%); and the distribution was largely similar in untreated as well as pre-treated cohorts. Furthermore, genomic alterations for each cancer type are described in Table 1. MSI high and TMB high (>10) were reported in 0.5% and 7.4% respectively. PDL1 positive IHC was reported in 3.2% of tissue samples, whereas HRD high (>50) was reported in 2.3% of the cohort of which the majority (11.5%) were from Upper GI tumors. Targetable genomic alterations were detected in 53.8% (181/336) of which 38.1%(69/181) received the suggested targeted therapy. Clinical response was seen as PR in 14.4% and CR in 2.8% of patients. Of 336 patients 4.76% received modified therapeutic regimens which differed from the standard of care, wherein median PFS was 8 mo [CI 95% (5.3-10.7)] while median OS was 55.1 mo [CI 95% (25.8-NA)]. Conclusions: This observational study outlines the potential benefit of personalizing treatment regimens in the management of solid organ cancers, especially in scenarios where standard-of-care regimens may have failed and the need to incorporate broad-spectrum NGS. [Table: see text]