Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis

Ralf Gutzmer, Caroline Robert, Carmen Loquai, Dirk Schadendorf, Nicholas Squittieri, Ramon Arntz, Serena Martelli, Reinhard Dummer, Ralf Gutzmer, Caroline Robert, Carmen Loquai, Dirk Schadendorf, Nicholas Squittieri, Ramon Arntz, Serena Martelli, Reinhard Dummer

Abstract

Background: The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily.

Methods: This phase 2, double-blind study randomized patients 1:2 to sonidegib 200:800 mg daily, respectively. Key endpoints included objective response rate (ORR), duration of response (DOR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). laBCC tumors were assessed by both mRECIST and ERIVANCE-like criteria. Per mRECIST, an overall response of CR was based on negative histology; photographic assessment of CR, PR (scar/fibrosis only), SD (scar/fibrosis only), or not available (NA); and a magnetic resonance imaging response of CR or NA. An overall response of CR was primarily based on negative histology using ERIVANCE-like criteria.

Results: Per mRECIST criteria, ORR (95% confidence interval [CI]) by central and investigator review for patients with laBCC (n = 66) was 56.1% (43.3-68.3%) and 71.2% (58.7-81.7%), respectively. CR per central review was achieved in 3 (4.5%) patients and PR, SD, and PD occurred in 34 (51.5%), 23 (34.8%), and 1 (1.5%) patient, respectively. Median (95% CI) DOR was 26.1 months (not estimable [NE]). Using ERIVANCE-like criteria, efficacy outcomes per central and investigator review were higher, with an ORR (95% CI) of 60.6% (47.8-72.4%) and 74.2% (62.0-84.2%), respectively. CR per central review was reached in 14 (21.2%) patients and PR, SD, and PD occurred in 26 (39.4%), 20 (30.3%), and 1 (1.5%) patient, respectively. DOR was unchanged with a median (95% CI) of 26.1 months (NE).

Conclusions: Overall, applying ERIVANCE-like criteria to patients with laBCC receiving sonidegib 200 mg daily yielded higher response rates vs mRECIST criteria.

Trial registration: BOLT registration: ClinicalTrials.gov ( NCT01327053 ) on March 30, 2011.

Keywords: Basal cell carcinoma; Hedgehog pathway inhibitor; Sonidegib; Tumor outcome; mRECIST.

Conflict of interest statement

RG serves as consultant to Almirall; Amgen; Bristol-Myers Squibb; Immunocore; Merck Serono; Merck Sharp & Dohme; Novartis; Pfizer; Pierre Fabre; Roche; Sanofi Genzyme; Sun Pharmaceutical Industries, Inc.; and 4SC; has received travel grants and honoraria for lectures from Almirall; Amgen; Bayer; Bristol-Myers Squibb; Merck Serono; Merck Sharp & Dohme; Novartis; Pierre Fabre; Roche; and Sun Pharmaceutical Industries, Inc.; and has received research funding from Amgen; Johnson & Johnson; Merck Serono; Novartis; and Sun Pharmaceutical Industries, Inc. CR has received consulting fees from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, and Sanofi. CL has acted as a speaker for, served on an advisory board for, and received honoraria from Bristol-Myers Squibb, Roche, Novartis, and Merck Sharp & Dohme. DS has acted as a speaker for, served on an advisory board for, received research funding from, and/or received honoraria from 4SC Discovery, Agenus, Amgen, Array BioPharma, AstraZeneca, Bristol-Myers Squibb, Grünenthal Group, Immunocore, Incyte, LEO Pharma, Merck Serono, Merck Sharp & Dohme, Mologen, Novartis, Pfizer, Philogen, Pierre Fabre, Regeneron Pharmaceuticals, Roche, Sanofi, and Sysmex. NS, RA, and SM are employees of Sun Pharmaceutical Industries, Inc. RD has served on advisory boards and as a consultant for Amgen; Bristol-Myers Squibb; Catalym; Merck Sharpe and Dohme; Novartis Pharmaceutical Corporation; Pierre Fabre; Roche; Sanofi; Second Genome; Sun Pharmaceutical Industries, Inc.; and Takeda.

© 2021. The Author(s).

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