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

Tsimberidou AM1, Hong DS2, Wheler JJ2,3, Falchook GS2,4, Janku F2, Naing A2, Fu S2, Piha-Paul S2, Cartwright C2, Broaddus RR5, Nogueras Gonzalez GM6, Hwu P7, Kurzrock R2,8.

Author information

1: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. atsimber@mdanderson.org.
2: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
3: Current Address: TScan Therapeutics, Waltham, USA.
4: Current Address: Sarah Cannon Research Institute, Nashville, USA.
5: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
6: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
7: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
8: Current Address: Moores Cancer Center-University of California San Diego, San Diego, USA.

Abstract

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.