Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine

Abstract

BackgroundIn 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS).Patients and methodsWe performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes ≤\u2009182) for patients with lethal/refractory advanced cancers referred to the Phase 1 Clinical Trials Program. Matched therapy, if available, was selected on the basis of genomics. Clinical trials varied over time and included investigational drugs against various targets (single agents or combinations). Patients were followed up for up to 10\u2009years.ResultsOf 3487 patients who underwent tumor molecular profiling, 1307 (37.5%) had ≥\u20091 alteration and received therapy (matched, 711; unmatched, 596; median age, 57\u2009years; 39% men). Most common tumors were gastrointestinal, gynecologic, breast, melanoma, and lung. Objective response rates were: matched 16.4%, unmatched 5.4% (p < .0001); objective response plus\xa0stable disease ≥\u20096 months rates were:\xa0matched\xa035.3% and\xa0unmatched 20.3%, (p < .001). Respective median progression-free survival: 4.0 and 2.8\u2009months (p < .0001); OS, 9.3 and 7.3\u2009months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (p < .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status >\u20091 (p < .001), liver metastases (p < .001), lactate dehydrogenase levels > upper limit of normal (p < .001), PI3K/AKT/mTOR pathway alterations (p < .001), and non-matched therapy (p < .001). The five independent factors predicting shorter OS were used to design a prognostic score.ConclusionsMatched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient’s risk of death is proposed.Trial registrationClinicalTrials.gov, NCT00851032, date of registration February 25, 2009.