Comprehensive multigene profiling impact on clinical decisions in patients with advanced cancers: A multicenter, retrospective analysis.

Abstract

e15163 Background: Comprehensive molecular profiling (CMP) via next generation sequencing (NGS) is currently applied in clinical practice and has enabled the detection of biomarkers of response to targeted treatment. Given the lack of the data about optimal range of analyzed alterations, the clinical usefulness of CMP has not been established. To address the challenges in incorporating genomics in treatment of oncology patients, we conducted a retrospective study. Methods: Preliminary analysis of NGS reports and clinical data of patients with advanced solid tumors was performed. CMP was conducted in 261 cancer patients (non-small cell lung cancer - 30,6%, colorectal cancer - 24,8%, pancreatic cancer - 7,4%, breast cancer- 6,2%; 59,3% were female, median number of prior systemic treatment lines was 2 (0-12)). In the present study, tumor molecular profile analysis was performed using 160 - 400 gene NGS panels, containing the majority of clinically significant genes for cancer treatment selection. We assessed the percentage of patients who were recommended to receive molecularly-matched therapy (MMT) after CMP, immunotherapy (IT) distribution of recommended therapies according to ESCAT tiers, median progression-free survival (PFS) – ratio ( = PFS after CMP / PFS before CMP, PFS2/PFS1), median PFS2. Results: MMT after CMP was recommended for 55 (21,1%) patients. ESCAT tiers could be assessed in 48 MMT patients (87%). For 31% of patients, administered therapy was considered as ESCAT I tier recommendation (data on mPFS2/1, mPFS2 not available). ESCAT tiers II, III, IV and IT administration were considered in 31, 8, 8 and 22% of patients respectively (detailed data is presented in Table 1). Most commonly altered genes were TP53 (53%), RAS (29%), APC (18%), CDKN2A/B (16%), PIK3CA(14%), NF1 (10%), BRCA1/2 (9%). Positive predictive factors for MMT after CMP were MSI-high status (HR 0,13, 95% CI 0,03 - 0,67), presence of EGFR alteration (HR 0,32, 95% CI 0,12 - 0,86). Presence of RAS mutation was considered a negative predictive factor (HR 2,78, 1,07 - 7,26). Conclusions: Available NGS panels offer a wide range of analyzed alterations that are not feasible in clinical practice. Most of the alterations that can cause impact on treatment plan can be detected with other methods than NGS. Further studies are needed to determine optimal range of alterations depending on tumor site. [Table: see text]