1111PD - Expanded access study of advanced bcc patients treated with the hedgehog-pathway inhibitor vismodegib

Date 29 September 2012
Event ESMO Congress 2012
Session Melanoma
Topics Anti-Cancer Agents & Biologic Therapy
Melanoma and other Skin Tumours
Presenter Glenn Weiss
Authors G.J. Weiss1, A. Oro2, A.L.S. Chang3, J.A. Solomon4, P. Lorusso5, O. Hamid6, D.M. Chen7, E. McKenna7, S. Feng7, J.D. Hainsworth8
  • 1Virginia G. Piper Cancer Center Clinical Trials, Scottsdale Healthcare, 85258 - Scottsdale/US
  • 2Department Of Dermatology, Stanford University School of Medicine, Stanford/US
  • 3Department Of Dermatology, Stanford University School of Medicine, 94063 - Redwood City/US
  • 4Clinical Research, Ameriderm Research, 32174 - Ormond Beach/US
  • 5Research Administration, Karmanos Cancer Institute, 48201 - Detroit/US
  • 6Melanoma Center, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 7Medical Affairs, Genentech, 94080 - South San Francisco/US
  • 8Oncology Research, Sarah Cannon Research Institute, Nashville/US

Abstract

Background

Patients (pts) with advanced basal cell carcinoma (aBCC; disease that is locally advanced [laBCC] or metastatic [mBCC]) have limited therapeutic alternatives. The Hedgehog signaling pathway is a key driver in the pathogenesis of BCC. In a pivotal Phase II study, vismodegib (Erivedge™)—a first-in-class small-molecule inhibitor of Hedgehog pathway signaling—demonstrated significant clinical activity in aBCC with an acceptable safety profile. This US-only expanded access study initiated prior to FDA approval, provided vismodegib for aBCC pts and further characterized its safety profile and clinical activity.

Methods

Pts with histologically confirmed mBCC or laBCC inappropriate for, or recurring after surgery or radiotherapy, received daily oral vismodegib 150 mg until disease progression or intolerable toxicity. Interim data for the first 96 pts, enrolled Jul 2010–Nov 2011, are summarized; final results will be presented at the meeting.

Results

Of 96 pts (52 laBCC, 44 mBCC), 74% were male; median age was 63 (28–100) years. Median disease duration from diagnosis was 3.6 (0.02–53.2) years. Prior treatments included surgery (92%) and radiotherapy (51%). Pts received vismodegib for a median of 4.3 (0.6–16.1) months (median follow-up [f-u] 4.7 [0.6–16.1] months). Treatment-emergent adverse events (AEs) of any grade in ≥15% pts were: muscle spasms (60.4%), dysgeusia (55.2%), alopecia (45.8%), diarrhea (17.7%), nausea (17.7%), and fatigue (17.7%), with median times to first event of 30, 36, 84, 27, 25, and 22 days, respectively. No serious AEs related to vismodegib were reported. Discontinuations (n = 26) were due to disease progression (n = 14), AEs (n = 3), death (n = 1), lost to f-u (n = 1), physician (n = 1) or subject decision (n = 5), or other (n = 1). Of 69 evaluable patients with RECIST-measurable disease, the investigator-assessed response rate was 20/40 (50%; 95% CI 34–66%) for laBCC and 10/29 (34%; 95% CI 18–54%) for mBCC. 16 pts (40%) with laBCC and 14 (48%) with mBCC had stable disease.

Conclusions

Incidence and severity of AEs and clinical activity reported in this analysis are similar to those reported in the pivotal study in pts with aBCC. Vismodegib is an effective treatment option for aBCC pts.

Disclosure

G.J. Weiss: Speaker's bureau: Genentech, Pfizer Funding to my institution: Genentech, Novartis, Eli Lilly, Infinity.

A. Oro: Trial funding: Genentech, Novartis, Infinity.

A.L.S. Chang: Studies sponsored: Genentech, Novartis, Infinity, NuSkin, Galderma.

J.A. Solomon: Advisory Committee/Group: Genentech

P.M. LoRusso: Research funding: Genentech Advisory Board: Genentech Speakers' Bureau: Genentech.

O. Hamid: Consulting fee: Genentech Speaker bureau: BMS, Lilly, Genentech, Dendreon Research fee: GSK, Roche, merck, ArQule, Morphotek, EISAI, Lilly, BMS, Millenium.

D.M. Chen: Employee: Genentech Shareholder: Genentech.

E. McKenna: Employee: Genentech Shareholder: Genentech.

S. Feng: Employee: Genentech Shareholder: Genentech.

All other authors have declared no conflicts of interest.