Predicting Severe Toxicity Of Targeted Therapies In Elderly Patients With Cancer (Pretoxe): A Multicenter, Prospective, And Retrospective Study.

11550 Background: It is crucial that targeted therapies are also studied in senior patients to establish predictive factors of severe toxicity. Methods: The PRETOXE study includes 3 multicentric independent cohorts of patients ≥70 years old with advanced solid tumor (2 retrospectives and one prospective) and treated with a tyrosine/threonine kinase inhibitor (TKI) as per drug label. Data on clinical and biological characteristics of the patient, disease and treatment were centrally collected at the beginning of the treatment. Primary endpoint is severe toxicity defined as treatment-related death, persistant or significant disability/incapacity, hospitalization or discontinuation of treatment for more than three weeks. Predictive factors of severe toxicity were first identified in a training retrospective cohort by multivariate analysis. Two independent cohorts ( retrospective and prospective) will be used for external validation. Results: 371 patients entered the study (training retrospective cohort n = 171, 46.1 %; validation retrospective cohort: n = 160, 43.1%, validation prospective cohort: n = 40, 10.8%). Median age was 74.0 (range 70.0-88.0) in the training retrospective cohort. 73 patients (42.7%) were male. The most frequent solid tumors were lung 64 (37.4%), breast 50 (29.2%), sarcomas 27 (15.8%), colon 10 (5.8%) and kidney 8 (4.7%). The five most frequent prescribed TKIs were everolimus 51 (29.8%), erlotinib 43 (25.1%), pazopanib 18 (10.5%), gefitinib 17 (9.9%) and regorafenib 14 (8.2%). The prescribed dose was lower than that recommended in the drug label in 32.1% of cases. 46 (26.9%) patients had a severe toxicity as per protocol definition in retrospective cohort: hospitalization 5 (10.9%), discontinuation of treatment more than 3 weeks 4 (8.7%), definitive discontinuation of treatment 38 (82.6%), persistent or significant disability/incapacity 14 (30.4%). On multivariate analysis, female gender, ≥3 concomitant medications and anti-angiogenic activity of TKI were independent predictive factors of severe toxicity. External validation on the other two independent cohorts (retrospective and prospective) will be presented at the meeting. Conclusions: One in four cancer patient ≥ 70 years old and treated with a TKI has severe toxicity impacting treatment outcome. The role of geriatric intervention to prevent such toxicities should be considered particularly in female patients, patients with ≥3 concomitant medications or when the TKI targets the VEGF receptors family. Clinical trial information: NCT02751827.