1125P - Patient-reported quality of life (QOL) with sonidegib (LDE225) in advanced basal cell carcinoma (BCC)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Melanoma and other Skin Tumours
Presenter Reinhard Dummer
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors R. Dummer1, R. Gutzmer2, M.R. Migden3, L. Dirix4, K. Lewis5, P. Combemale6, K. Higuchi7, S. Gogov8, T. Yi9, R. Herd10, R. Kudchadkar11, U. Trefzer12, J. Lear13, D. Sellami14, A. Guminski15
  • 1Department Of Dermatology, UniversitätsSpital Zürich, Skin Cancer Center University Hospital, 8091 - Zürich/CH
  • 2Department Of Dermatology And Allergy, Skin Cancer Center, Medizinische Hochschule Hannover, Hannover/DE
  • 3Departments Of Dermatology And Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston/US
  • 4Clinical Trials Oncology, Oncologisch Centrum Sint-Augustinus, Antwerp/BE
  • 5Division Of Medical Oncology, University of Colorado Cancer Center, Aurora/US
  • 6Oncodermatology Unit, Centre Leon Bérard, Lyon/FR
  • 7Worldwide Health Outcomes, Value, And Access, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 8Oncology Global Development, Novartis Pharma AG, Basel/CH
  • 9Biometrics & Data Management, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 10Department Of Dermatology, Glasgow Royal Infirmary, Glasgow/GB
  • 11Department Of Cutaneous Oncology, Moffitt Cancer Center, Tampa/US
  • 12Department Of Dermatology, Allergology, And Tumor Therapy, Dermatologikum Berlin, Berlin/DE
  • 13Department Of Dermatology, Manchester Royal Infirmary, Manchester/GB
  • 14Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 15Department Of Medical Oncology, Royal North Shore Hospital, St Leonards/AU

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 (H&N35). Prespecified subscale scores included physical functioning, social functioning, pain, and fatigue for C30, and trouble with social contact, head and neck pain, and weight loss for H&N35.

Results

Questionnaires were completed at baseline (BL) and ≥ 1 post-BL time point by 88.7% (C30) and 90.0% (H&N35) of pts. Maintenance or improvement of scores on the C30 and H&N35 scales was experienced by the majority of pts, with consistent effects in those with LaBCC and mBCC (Table). Descriptive analysis of mean scores generally showed maintenance in each scale through week 73 with both doses. Median time to deterioration (> 10-point worsening without subsequent improvement) was 13.7 months for fatigue and 16.6 months for weight loss, and not estimable (NE) for other scales with 200 mg; 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 H&N35
Trouble with social contact N = 58 N = 13 N = 110 N = 19
Improvement from BL 25 (43.1) 4 (30.8) 33 (30.0) 8 (42.1)
No change from BL 27 (46.6) 7 (53.8) 68 (61.8) 9 (47.4)
Head and neck pain N = 60 N = 13 N = 112 N = 20
Improvement from BL 11 (18.3) 3 (23.1) 20 (17.9) 4 (20.0)
No change from BL 47 (78.3) 9 (69.2) 78 (69.6) 12 (60.0)
Weight loss N = 58 N = 12 N = 110 N = 19
Improvement from BL 9 (15.5) 2 (16.7) 8 (7.3) 5 (26.3)
No change from BL 49 (84.5) 8 (66.7) 89 (80.9) 14 (73.7)

a Pts who completed the scale at both BL and ≥ 1 post-BL time point. b Based on best score change from post-BL evaluations.

Disclosure

R. Dummer: has served an advisory role, received honoraria and research funding from Astra Zeneca, Novartis, Cephalon, MSD, BMS, GSK, Roche, Amgen and Bayer; 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.