Precision medicine is associated with favorable outcomes in selected patients. We initiated IMPACT 2, a randomized study to compare PFS in patients with metastatic cancer treated on the basis of tumor genomic profiling results vs. those whose treatment was not selected based on genomic analysis. Herein, we assessed the association between patient characteristics and overall survival (OS).
Patients with advanced, metastatic cancer underwent tumor biopsy and genomic profiling (Foundation One). Variants were filtered to eliminate germline mutations (annotation, ANNOVAR) and artifacts. Patients were presented at tumor board and were randomized if they met criteria for clinical trials. OS was measured from enrollment on study until last follow-up or death from any cause.
From 5/2014 to 4/2017, 320 of 391 enrolled patients completed tumor profiling. Baseline characteristics (n = 320) were as follows: men, 47%; median age, 63 yrs (range, 25-83); performance status 1, 88%; median no. of prior therapies, 3 (range, 0-14); liver metastases, 40%; albumin < 3.5 g/L, 12%; LDH > 618 IU/L, 29%; platelet count > or < the normal limits, 15%. Most common tumor types were head and neck, 19%; gastrointestinal, 16%; and lung, 11%. Most frequently mutated genes: TP53, 42%; KRAS,16%; PIK3CA,12%; and CDKN2A, 11%. Of 320 patients, 69 (22%) were randomized; of the remaining 251 patients, 153 (61%) received other treatment (investigational or standard). Results of multivariate analyses for OS are displayed below. 449PDMultivariate analysis, OS Risk Factor HR 95% CI P Age ≥ 60 yrs 1.02 1.00-1.03 .009 Liver metastases 1.43 1.07-1.91 .02 LDH > 618 IU/L 2.19 1.61-2.97 < .0001 Albumin < 3.5 g/dL 1.90 1.26-2.87 .002 KRAS mutated 2.27 1.57-3.28 < .0001 TP53 mutated 1.38 1.04-1.84 .03
In patients with metastatic cancer, age < 60 yrs, absence of liver metastases, normal albumin and LDH levels, and absence of KRAS or TP53 mutations were independent factors predicting longer OS. We demonstrated the feasibility of molecular profiling using newly obtained tumor biopsies and treating patients prospectively. The study is ongoing. Outcomes for randomized patients are awaited upon completion of the study.
www.clinicaltrials.gov NCT02152254, First posted June 2, 2014.
The authors.
Foundation Medicine.
A.M. Tsimberidou: Research grant / Funding (institution): IMMATICS; Research grant / Funding (institution): Tempus; Research grant / Funding (institution): Parker Institute for Cancer Immunotherapy; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Baxalta; Research grant / Funding (institution): Foundation Medicine; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Placon Therapeutics; Research grant / Funding (institution): Karus Therapeutics; Research grant / Funding (institution): Tvardi; Research grant / Funding (institution): OBI Pharma; Advisory / Consultancy: Roche, Europe; Advisory / Consultancy: Covance; Advisory / Consultancy: Genentech. D.S. Hong: Research grant / Funding (self): Adaptimmune; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Bayer; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Daichi-Sanko; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Genmab; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Infinity; Research grant / Funding (institution): Kite; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): LOXO; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Molecular Template; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.