ABSTRACT Aim: Advanced BCC can cause considerable morbidity and severe disfigurement, leading to emotional and psychological distress and reduced QOL. The hedgehog (Hh) pathway is aberrantly activated in ≥ 95% of BCCs. Sonidegib blocks the Hh pathway by selective inhibition of smoothened. In a phase 2 study (BOLT; NCT01327053), patients (pts) with advanced BCC achieved meaningful disease control with sonidegib. The impact on pt-reported QOL is presented here. Methods: Pts with locally advanced BCC (LaBCC) not amenable to curative surgery or radiotherapy (n = 194) or metastatic BCC (mBCC; n = 36) were randomized to receive sonidegib 200 or 800 mg (1:2) once daily. QOL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the associated Head and Neck cancer module (HN and 11.1, 11.3, 5.6, and 16.5 months for physical functioning, social functioning, fatigue, and weight loss, respectively, and NE for other scales with 800 mg. Conclusions: Overall, pts treated with sonidegib in the BOLT trial maintained or improved their functioning and QOL, supporting the treatment effect observed in pts with advanced BCC and the favorable tolerability of sonidegib. Table. Pt-Reported QOL in Pts With Advanced BCC Treated With Sonidegib. Pts Na n (%)b Sonidegib 200 mg once daily Sonidegib 800 mg once daily LaBCC mBCC LaBCC MBCC EORTC QLQ-C30 Physical functioning N = 61 N = 13 N = 110 N = 20 Improvement from BL 22 (36.1) 9 (69.2) 35 (31.8) 8 (40.0) No change from BL 29 (47.5) 3 (23.1) 38 (34.5) 10 (50.0) Social functioning N = 61 N = 13 N = 109 N = 20 Improvement from BL 16 (26.2) 5 (38.5) 22 (20.2) 7 (35.0) No change from BL 40 (65.6) 6 (46.2) 75 (68.8) 12 (60.0) Pain N = 61 N = 13 N = 110 N = 20 Improvement from BL 19 (31.1) 6 (46.2) 36 (32.7) 11 (55.0) No change from BL 36 (59.0) 7 (53.8) 52 (47.3) 7 (35.0) Fatigue N = 61 N = 13 N = 109 N = 20 Improvement from BL 23 (37.7) 6 (46.2) 21 (19.3) 8 (40.0) No change from BL 26 (42.6) 6 (46.2) 55 (50.5) 8 (40.0) EORTC HN R. Gutzmer: has served an advisory role for Roche, MSD, BMS, Novartis (NVS), GSK; received honoraria from Roche, BMS, MSD, Janssen, Amgen, GSK, Almirall, NVS, MerckSerono, Pfizer; and received research funding from Roche, NVS, Pfizer; M.R. Migden: has served an advisory role and received honoraria from Genentech, Novartis, Lilly; received institutional research funding from Genentech; provided expert testimony on behalf of Novartis; K. Higuchi: Keiko Higuchi is employed by Novartis; S. Gogov: is employed by Novartis and owns stock; T. Yi: Dr. Tingting Yi is employed by Novartis and owns stock; R. Herd: has received research funding from Novartis; R. Kudchadkar: has served an advisory role and received honoraria from Genentech and BMS; U. Trefzer: has served an advisory role and received honoraria from Roche; J. Lear: has received honoraria from Novartis; D. Sellami: is employed by Novartis and owns stock; A. Guminski: has served an advisory role for Novartis. All other authors have declared no conflicts of interest.