Subgroup analysis of patients (pts) with Gorlin syndrome treated with vismodegib (VISMO) in the STEVIE study

Background

VISMO, a first-in-class Hedgehog pathway inhibitor, is approved (US and EU) in adults with locally advanced BCC (laBCC) or metastatic BCC (mBCC). STEVIE (ClinicalTrials.gov NCT1367665), is evaluating safety and efficacy of VISMO in pts with advanced BCC, including pts with Gorlin syndrome, a hereditary condition characterised by multiple BCCs. Data from the subset of Gorlin pts in the primary analysis are presented.

Methods

Pts with Gorlin syndrome could enrol in the study if they met protocol-defined criteria for laBCC or mBCC. Pts received oral VISMO 150 mg/day until progressive disease, unacceptable toxicity, or withdrawal. The primary outcome was safety. Secondary outcomes included efficacy and quality of life.

Results

The analysis includes 219 Gorlin pts (laBCC, n = 214; mBCC, n = 5) with a median age of 52 (range 18–88) years. Median treatment duration was 374 days and median dose intensity was 95.8%. At cut-off (March 16, 2015), all Gorlin pts experienced ≥1 treatment-emergent adverse event (TEAE). Most common TEAEs were muscle spasm (78.1%), alopecia (78.1%), dysgeusia (58.0%), diarrhoea (30.6%), nausea (23.3%), fatigue (23.3%) and asthenia (20.5%). Most TEAEs (56%) were grade 1–2 and serious TEAEs were reported in 17.8% of pts. Treatment discontinuation due to TEAEs occurred in 29.2% of pts and included muscle spasms (8.2%), alopecia (6.8%) and dysgeusia (5.0%); most were grade 1–2 (20.6%). Five pts (2.3%) died due to grade 5 AEs (n = 4) and other reasons (n = 1). All grade 5 AEs presented with confounding factors and assessed as unrelated to VISMO per investigator. Best overall response (Response Evaluation Criteria in Solid Tumors version 1.1; investigator assessed) was 81.7% (95% confidence interval [CI] 75.8–86.6). Median time to response was 2.9 months (95% CI 2.8–3.7). Median progression-free survival was 32.5 months (95% CI 29.4–not estimable [NE]). Median duration of response was 28.8 months (95% CI 24.8–NE).

Conclusions

TEAES reported in Gorlin pts are similar to those observed in previous studies of VISMO. The results confirmed clinical efficacy of VISMO in Gorlin pts, and support the use of VISMO in this pt population.

Clinical trial identification

NCT01367665

Legal entity responsible for the study

Roche-Genentech

Funding

Roche-Genentech

Disclosure

N. Basset-Seguin: Employment: Genentech Consultant/Advisory: Novartis, Roche, Leo Pharma, Galderma, Pierre Fabre Patents, Royalties, Other: Genentech Travel, Accommodation, Expenses: Roche, Galderma, Leo Pharma. J. Hansson: Consultant/Advisory: BMS, GSK, MSD/Merck, Novartis,Roche Pharma Trial Grants/Research Funding: Amgen, BMS, GSK, MSD/Merck, Novartis, Roche. R. Kunstfeld: Honoraria: Roche, Novartis, Menarini, Meda‐Pharma Consulting/Advisory Role: Roche, Novartis, Menarini, Meda‐Pharma, Spirig, Leo Pharma. J.J. Grob: Honoraria: GSK, Roche, BMS Consulting/Advisory: GSK, BMS, Roche, Amgen, Merck, Novartis Speaker Bureau: GSK Research: Roche, BMS Travel, Accommodations, Expenses: Roche. B. Dreno: Consulting/Advisory: BMS, GSK, Roche, Novartis Speaker Bureau: BMS, GSK, Roche Research: BMS, GSK Travel, Accommodations, Expenses: BMS, Roche. L. Mortier: Research funding (institution received): Roche, BMS, GSK, CSO, and Novartis. P.A. Ascierto: Consultant/Advisory: BMS, Roche/Genentech, MSD, Ventana, Novartis, Amgen, Array Research: BMS, Roche/Genentech, Ventana. N. Dimier: Employment: Roche Stock/Other Ownership: Roche, GSK. A. Fittipaldo: Employee, Stockholder: Hoffman-La Roche. I. Xynos: Advisory Board, Honoraria, Investigator: Roche/Genentech. A. Hauschild: Consulting/Advisory, Honoraria, Trial Grants: Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, Roche Pharma.