Precision medicine and actionable alterations in lung cancer.

Abstract

e20707 Background: In recent years, healthcare centers have become more reliant on the advent of new technology, testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians, researchers, and the medical community. This aggregate of information stands to be a powerful tool that can enable one to perform highly complex investigations more easily, as well as aid physicians in their efforts to provide personalized medicine to patients. However, in order to take advantage of vital clinical and research data, we must initially make an effort to create an effective infrastructure for the collection, storage, utilization, and protection of this information with uniquely designed disease-specific registries that have adequate informatics support to allow for the collection of a large number of patients. Methods: In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic and clinical data in a recently created thoracic patient registry. Results: Of the 415 patients in the analysis, 59% (n = 245) were female; the median age was 64 (range, 22-92) years with a median OS of 33.29 months (95% CI, 29.77-39.48). The frequency of the most commonly occurring oncogenes was 50% EGFR (n = 207/415), 28% KRAS (n = 97/352), and 7% ALK rearrangement (n = 28/377), while the most commonly occurring tumor suppressor genes consisted of TP53 (n = 140/283 [49%]), LRP1B (n = 63/228 [28%]), and STK11 (n = 39/278 [14%]). The most common actionable alterations were identified in EGFR L858R/exon 19 deletion (n = 177/415 [42.7%]), ALK rearrangement (n = 28/377 [7.4%]), ROS1 rearrangement (n = 3/257 [1.2%]), BRAF V600E (n = 7/288 [2.4%]) and MET exon 14 splice site/deletion (n = 7/287 [2.4%]). While there were no median OS differences in patients who were tested under a broad-panel vs small-panel (33.4 months vs 33.5 months; 95% CI; P = 0.36), there was a discernible difference in survival for 222 patients, who had an actionable alteration, with a median OS of 39.8 months as compared to 193 patients who were wild-type with a median OS of 26.0 months (95% CI; P < 0.001). In addition, we identified an unprecedented number of patients with actionable alterations [53.5% (222/415)], including distinct individual alteration rates, as compared with 15.0% and 22.3% in TCGA and GENIE respectively. Conclusions: The use of patient registries, focused genomic panels and the appropriate use of clinical guidelines in community and academic settings may influence cohort selection for clinical trials and improve survival outcomes.