Background: In the wake of personalized medicine in Oncology, genetic tumor profiling has become a cornerstone to select patients (pts) for clinical trials, exploring new molecular targeted agents. Methods: As part of the Vall d’Hebron University Hospital Molecular Prescreening/Phase 1 Trials Program, advanced gynecologic cancer (GYNT) pts were screened for molecular alterations (MA) (KRAS/PIK3CA/AKT/BRAF mutations [mut]; PD-L1 expression; PTEN loss, H score<50) and allocated to receive matched targeted therapy (MTT). We present a summary of molecular characteristics and clinical outcomes, using previous treatment as reference to evaluate potential efficacy. Results: From 01/2012 to 11/2013, 86 consecutive GYNT pts (mean age: 53.3 yrs; median no. previous treatments: 3 [0-7]) were screened for MA; 60 (69.8%) ovarian (OvC), 18 (20.9%) endometrial (EC) and 8 (9.3%) cervical carcinomas (CC). Median time from diagnosis to molecular analysis was 2.96 yrs. MA were identified in 23 pts (26.7%) as specified in Table 1: 5 type-I/8 type-II OvC; 4 type-I/4 type-II EC; 2 CC. Fifteen pts received MTT according to MA. Six harbored PIK3CA mut; 5 were treated with α-specific PI3K inh and 1 with PI3K/mTOR inh. Pts with KRAS mut (8) received MEK inh-based combinations: 6 MEK/PI3K inh, 1 MEK/AKT inh, 1 MEK/IGFR1 inh. A double-mutated pt (PIK3CA/KRAS mut) was treated with mTOR inh. Median PFS of the MTT population was 19.5 wks [CI95%: 10.7-NA], slightly superior to 17.0 wks [CI95%: 12.9-38.6] achieved with the immediately previous line of systemic therapy (p=0.121). Conclusions: Treatment based on MA may improve clinical outcome in heavily pre-treated GYNT, as results in this analysis were superior to standard therapy. Statistical significance was not reached, probably due to small sample size. Our work warrants further studies of MTT in larger less pre-treated population.

*Double mut: 1 pt endometrioid EC.