Background: The prognosis of patients (pts) with PSCC is primarily depending on the involvement of regional lymph nodes. Owing to the limited efficacy of chemotherapy, new drugs are warranted. Dacomitinib (Daco) is a potent, irreversible TKI of human EGFR/HER1, HER2 and HER4. Methods: In a phase 2 study (NCT01728233), pts received Daco 45 mg/d, orally, continuously. Inclusion criteria were SCC histology, and clinical stage N2-3 or M1; no prior chemotherapy was allowed. Computed tomography (CT) and PET/CT scans were repeated q8 weeks. Responding (R) pts with locally-advanced (LA) PSCC were offered radical surgery. The primary endpoint was the objective response-rate (ORR=CR+PR according to RECIST v1.1). Stopping rules based on the Bayesian posterior probability (PP) were set; the target was to demonstrate that the ORR exceeded 20%. Translational analyses on pre-Daco tumor samples included: EGFR and HER2 amplification, in-situ hybridization for HPV, and next generation sequencing. Results: From 06/13 to 010/16, 28 patients were treated. 8 (28.6%) had visceral metastases. 50% had pelvic and 60.7% clinically-involved bilateral LN. 1 CR + 8 PR were obtained (ORR=32.1%, 80% credibility interval 21.0-43.0%). The median follow up was 19.8 months (IQR: 6.3-25.7); 12-m PFS was 26.2% (95%CI: 13.2-51.9); 12-m OS was 54.9% (95%CI: 36.4-82.8). The median OS of LA pts was 20 months (IQR: 11.1-NR). The current Bayesian PP of exceeding the 20% ORR target is 92.3%. Grade 3 adverse events (skin rash) were seen in 3 pts (10.7%). The median drug exposure was 2.2 months. Tissue samples from 25 pts were analyzed. Only 2 pts were HPV+ (1SD, 1PD). EGFR ampl was found in 4 pts (1 CR, 1 PR, 2 SD) and it was confirmed in all post-Daco samples. TERT mutations (60%) were found in responders only, PI3K/mTOR pathway gene mutations in 42.9% R vs 8.3% non responders, IGF2R in 40% and 20%, respectively. Mutations were largely consistent between matched pre- and post-therapy samples in 7 evaluated pts. Conclusions: Daco was active in advanced PSCC and provided the best ORR with a single agent in PSCC. The biology underlying response to Daco seems to be independent from HER-pathway alterations. The frontline therapy can provide a suitable window of opportunity to test new drugs in PSCC.

Note: This abstract was not presented at the meeting.

Citation Format: Andrea Necchi, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai, Giuseppina Calareso, Elena Togliardi, Maurizio Colecchia, Federica Perrone, Annunziata Gloghini, Luigi Mariani, Roberto Salvioni. First-line therapy with dacomitinib, an orally available pan-her tyrosine kinase inhibitor, for locally-advanced or metastatic penile squamous cell carcinoma: Results of an open label, single-arm, single-center, phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT139. doi:10.1158/1538-7445.AM2017-CT139