scholarly journals 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

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ralf Gutzmer ◽  
Caroline Robert ◽  
Carmen Loquai ◽  
Dirk Schadendorf ◽  
Nicholas Squittieri ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Objective Response ◽  
Locally Advanced ◽  
Double Blind Study ◽  
Double Blind ◽  
Overall Response ◽  
Link Type ◽  
Advanced Basal Cell Carcinoma

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.

Randomized, double-blind study of sonidegib (LDE225) in patients (pts) with locally advanced (La) or metastatic (m) basal-cell carcinoma (BCC)

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 9009a-9009a ◽  
Author(s):  
Michael Robert Migden ◽  
Alexander David Guminski ◽  
Ralf Gutzmer ◽  
Luc Yves Dirix ◽  
Karl D. Lewis ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Locally Advanced ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind

A phase I study of CX-4945 administered orally twice daily to patients with advanced basal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS10080-TPS10080
Author(s):  
Zeynep Eroglu ◽  
Charles Lance Cowey ◽  
John Soong ◽  
Daniel McCormick ◽  
Phoebe Fan ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Target Genes ◽  
Objective Response ◽  
Locally Advanced ◽  
Eligibility Criteria ◽  
Hh Signaling ◽  
Advanced Basal Cell Carcinoma

TPS10080 Background: Smoothened inhibitors (SMOi) targeting the Hedgehog (Hh) pathway have been approved for the treatment of patients with locally advanced Basal Cell Carcinoma (laBCC) or metastatic BCC (mBCC). Unfortunately, resistance against SMO inhibitors (SMOi) can develop. Targeting the signaling cascade downstream of SMO, in this case via a novel small molecule inhibitor, could obviate this issue. Casein Kinase 2 (CK2) affects the terminal component of the Hh signaling pathway by promoting Gli2 stability and Gli2’s interaction with target genes. Given the interplay between CK2 and GLI-2 and the importance of Hh signaling activation, CX-4945, a potent CK2 inhibitor, may provide benefits for the BCC patients with resistance or intolerance to SMOi. Methods: A phase I trial (NCT03897036) to explore various treatment durations of CX-4945 was designed for patients with laBCC or mBCC; with endpoints include safety (CTCAE v5) and objective response rate by RECIST 1.0 for mBCC and composite response for laBCC. Major eligibility criteria include progression or intolerability to SMO inhibitors; laBCC patients must not be surgical candidates and must have received prior radiation unless contraindicated, and basosquamous histology is excluded. The first phase of the trial uses a 3+3 design to test the tolerance of a CX-4945 dose of 1000 mg bid for a duration of 28 days continuously. If 2 out of 3, or 2 out of 6 patients experience a DLT, the regimen of 1000 mg bid for 21 days followed by 7 days off (already tested in prior CX-4945 Phase I trials in other tumor types) will be selected as the recommend phase 2 dose (RP2D). Upon determining the RP2D, a dose-expansion phase will further evaluateCX-4945 in two cohorts (laBCC & mBCC), with 10 patients enrolled in each. Currently, we are enrolling patients and collecting sufficient data for the determination of RP2D in this patient population; thus, further assessments are required to determine the safety, tolerability, and efficacy of CX-4945 in advanced BCC. Clinical trial information: NCT03897036.

Follow-Up of Patients With Complete Remission of Locally Advanced Basal Cell Carcinoma After Vismodegib Discontinuation: A Multicenter French Study of 116 Patients

2019 ◽  
Vol 37 (34) ◽  
pp. 3275-3282 ◽  
Author(s):  
Florian Herms ◽  
Jerome Lambert ◽  
Jean-Jacques Grob ◽  
Luc Haudebourg ◽  
Martine Bagot ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Basal Cell Carcinoma

PURPOSE Vismodegib is a hedgehog pathway inhibitor indicated for the treatment of locally advanced basal cell carcinoma (laBCC), with an objective response rate of 65%, including a 32% complete response (CR). However, adverse effects often lead to drug discontinuation. The objective of our study was to evaluate long-term responses, predictive factors, and management of relapse after vismodegib discontinuation. METHODS An observational retrospective study was conducted in nine French oncodermatology units. We included patients with laBCC with CR on vismodegib who discontinued treatment between March 2012 and January 2016; we reviewed charts up to June 2016. The primary objective was to evaluate median relapse-free survival (RFS). Secondary objectives were risk factors associated with RFS, relapse, and death and treatment modalities after relapse and their efficacy. RESULTS One hundred sixteen patients with laBCC were included. The median RFS was 18.4 months (95% CI, 13.5 to 24.8 months). The RFS rate at 36 months was 35.4% (95% CI, 22.5% to 47.9%) for the total population and 40.0% (95% CI, 25.7% to 53.7%) for patients without Gorlin syndrome. LaBCC to the limbs and trunk was the only variable independently associated with a higher risk of relapse (hazard ratio, 2.77; 95% CI, 1.23 to 6.22; P = .019). Twenty-seven patients (50%) who experienced relapse during follow-up were retreated with vismodegib, with an objective response in 23 (objective response rate, 85%; CR rate, 37%; partial response rate, 48%) and eligibility for surgery in 24 (42%). CONCLUSION Long-term response after vismodegib discontinuation is frequent. Most patients who experience a relapse still respond to vismodegib rechallenge.

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