1876P - Actionable mutations and overall survival in 3,211 patients with cancer: The Hellenic cooperative oncology group precision medicine initiative

Abstract

Background: We evaluated the impact of tumor type and molecular profiling on overall survival of patients (pts) with cancer referred to Medical Oncology Departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Methods: Pts referred from 1989 to 2017 had molecular testing (for research) of archival tumor tissue collected at the time of diagnosis (stage I-III, 82%; stage IV, 18%). Tumor-specific (e.g. breast, colon) gene panels (45-101 genes) were used to identify pathogenic mutations in clinically relevant genes. Deep sequencing was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki and HeCOG. Mutation annotation was performed at MD Anderson Cancer Center. All pts received standard-of-care anticancer therapy. Results: We analyzed 3,211 pts (median age, 58 years; men, 29%) with informative sequencing data. Results by tumor type and molecular pathway are shown in the table. Overall, 1,193 (37%) pts had ≥1 actionable alterations [115 (3.6%) ≥4]. The most common affected pathways were PI3K, RAF/MEK, homologous recombination repair (HRR), and tyrosine kinase; 294 (9.2%) pts had alterations in > 1 pathways. The median follow-up of alive patients is 7.48 years (yrs) (95%CI, 7.36-7.59). Of 3,211 pts, 1,060 (33.01%) have died. The median overall survival is 16.08 yrs (95%CI, 13.25-16.75). Of pts with breast cancer and actionable mutations, the 5-yr survival rates were: stage I-III (n = 501) 88.8%; stage IV (n = 14), 51.1% (p<.0001). Of pts with colorectal cancer and actionable alterations, the 5-yr survival rates were: stage I-III (n = 299), 76.5%; stage IV (n = 50), 15.2% (p<.0001). Conclusions: Tumor sequencing revealed clinically relevant genomic mutations in several molecular pathways. Prospective clinical trials validating the clinical utility of tumor profiling are warranted. Legal entity responsible for the study: Hellenic Cooperative Oncology Group. Funding: Hellenic Cooperative Oncology Group. Disclosure: All authors have declared no conflicts of interest.Table: 1876PTotal NN with actionable alterations%Overall SurvivalTumor typeMedian, Years (95% CI)5-yr OS, % (95% CI)Breast1,96452727NR87.8 (85.0-90.7)Colorectal53335967NR68.0 (63.2-73.2)Pancreatic188123650.82 (.65-.98)-Nasopharyngeal14477548.92 (6.68-NR)65.2 (54.7-77.7)Brain13124184.54 (1.69-9.71)46.9 (29.9-73.6)Gastric10111114.18 (1.04-NR)39.8 (17.8-88.9)Biliary Tract802633NDOvarian7046663.24 (2.18-5.32)36.4 (24.7-53.5)Total3,2111,1933713.23 (10.6-NR)68.6 (65.9-71.4)PathwayTotal testedN with actionable alterations%PI3K/AKT/mTOR3,2116362016.08 (13.23- NR)82.3 (79.3-85.4)MEK/RAF3,211459146.4 (4.08-8.92)52.3 (47.7-57.3)HRR3,21126087.84 (5.33-NR)56.8 (50.7-63.5)Tyrosine kinase3,2111615NR69.2 (62.0-77.3) Open table in a new tab