CAPRA: Safety, efficacy, and translational biomarkers of weekly everolimus, carboplatin, and paclitaxel as induction therapy for locally advanced head and neck squamous cell carcinoma (HNSCC).

6036 Background: ThePI3K/mTOR pathway is activated in >50% of HNSCC with preclinical synergism between everolimus and carboplatin/paclitaxel. Methods: Patients (pts) with untreated locally advanced HNSCC with ECOG PS<2 received 9 consecutive weekly (w) cycles (cy) of CAPRA combining everolimus (30 mg/w at dose-level 1 then 50 mg/w at dose-level 2) with carboplatin (AUC2) and paclitaxel (60 mg/m2) followed by chemoradiotherapy. Endpoints were safety (CTCv3.0), antitumor activity (RECIST1.1), pharmacodynamic biomarkers on tumor biopsy. Results: A total of 50 pts with stage IV HNSCC (41 males, 9 females, median age 61) were enrolled. Among 7 patients included in the phase I, no dose-limiting toxicity was reported and the recommended dose (RD) of everolimus was 50 mg/w. Safety evaluation in 46 pts treated at RD for 325 cy and a mean number cy/pt of 7.1 (95%CI: 6.3-7.8) showed grade (Gr) 1-2 adverse events consisting of asthenia (50%), nausea/vomiting (28%), alopecia (26%), mucositis (24%), and constipation (2...