Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine. J Hematol Oncol 2019 Dec 30;12(1):145
Date
01/01/2020Pubmed ID
31888672Pubmed Central ID
PMC6937824DOI
10.1186/s13045-019-0835-1Scopus ID
2-s2.0-85077235900 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
BACKGROUND: In 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 METHODS: We performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes ≤ 182) 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 years.
RESULTS: Of 3487 patients who underwent tumor molecular profiling, 1307 (37.5%) had ≥ 1 alteration and received therapy (matched, 711; unmatched, 596; median age, 57 years; 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 stable disease ≥ 6 months rates were: matched 35.3% and unmatched 20.3%, (p < .001). Respective median progression-free survival: 4.0 and 2.8 months (p < .0001); OS, 9.3 and 7.3 months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (p < .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status > 1 (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.
CONCLUSIONS: Matched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient's risk of death is proposed.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00851032, date of registration February 25, 2009.
Author List
Tsimberidou AM, Hong DS, Wheler JJ, Falchook GS, Janku F, Naing A, Fu S, Piha-Paul S, Cartwright C, Broaddus RR, Nogueras Gonzalez GM, Hwu P, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Biomarkers, Tumor
Case-Control Studies
Clinical Trials, Phase I as Topic
Female
Follow-Up Studies
Humans
Liver Neoplasms
Male
Middle Aged
Molecular Targeted Therapy
Neoplasms
Precision Medicine
Prognosis
Protein Kinase Inhibitors
Protein Kinases
Response Evaluation Criteria in Solid Tumors
Survival Rate
Young Adult
