First-line avelumab treatment in patients with metastatic Merkel cell carcinoma: 4-year follow-up from part B of the JAVELIN Merkel 200 study.

BACKGROUND: Results from the JAVELIN Merkel 200 study led to the approval of avelumab [an anti-programmed death-ligand 1 (PD-L1) antibody] for the treatment of metastatic Merkel cell carcinoma (mMCC) in multiple countries and its inclusion in the treatment guidelines as a preferred or recommended therapy in this setting. Here, we report 4-year follow-up results from the cohort of patients with mMCC who received avelumab as first-line treatment. PATIENTS AND METHODS: In part B of JAVELIN Merkel 200, a single-arm, open-label, phase II study, patients with mMCC who had not received prior systemic therapy for metastatic disease received avelumab 10 mg/kg via intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term overall survival (OS), patient disposition, and subsequent treatment were analyzed. RESULTS: In total, 116 patients received first-line avelumab. At the data cutoff (2 February 2022), the median follow-up was 54.3 months (range 48.0-69.7 months). Seven patients (6.0%) remained on treatment and an additional 21 patients remained in follow-up (18.1%); 72 patients (62.1%) had died. The median OS was 20.3 months [95% confidence interval (CI) 12.4-42.0 months], with a 4-year OS rate of 38% (95% CI 29% to 47%). In patients with PD-L1+ or PD-L1- tumors, the 4-year OS rate was 48% (95% CI 26% to 67%) and 35% (95% CI 25% to 45%), respectively. In total, 48 patients (41.4%) received poststudy anticancer drug therapy, most commonly etoposide (20.7%), carboplatin (19.0%), and avelumab (12.1%). CONCLUSIONS: Avelumab first-line monotherapy in patients with mMCC resulted in meaningful long-term OS, which compared favorably with historical studies of first-line chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.

[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial.

AIM: ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAFV600-mutated melanoma. METHODS: In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1). Primary outcome was PFS1 (time from start of run-in until PD1 or death). OS and safety were also assessed. RESULTS: Of 185 patients enroled between November 2016 and December 2019, 135 were randomly assigned after the run-in period (Arm A, n = 69; Arm B, n = 66). Median PFS1 was significantly longer in Arm A versus Arm B (13.9 versus 5.9months; hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.37-0.84; PStratified=0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69-2.16; PStratified=0.389); 2-year OS was higher in Arm B versus Arm A (67%; 95%CI, 53-78 versus 58%; 95%CI, 45-70). Grade 3/4 AEs occurred in 55% of patients in Arm A and 64% in Arm B; treatment-related AEs led to discontinuation of any drug in 7% and 9% of patients, respectively. CONCLUSION: In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2years compared with continued TT.

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006.

BACKGROUND: Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized. PATIENTS AND METHODS: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi ± MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled. RESULTS: At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi ± MEKi for 59 (10.6%) [33 received BRAFi + MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi ± MEKi naïve]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi ± MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi ± MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi ± MEKi initiation was 12.9 months. ORR for BRAFi ± MEKi-naïve patients who received subsequent BRAFi ± MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR). CONCLUSIONS: Ipilimumab and BRAFi ± MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.

Position statement on classification of basal cell carcinomas. Part 1: unsupervised clustering of experts as a way to build an operational classification of advanced basal cell carcinoma based on pattern recognition.

BACKGROUND: No simple classification system has emerged for 'advanced basal cell carcinomas', and more generally for all difficult-to-treat BCCs (DTT-BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists. OBJECTIVE: To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions. METHOD: Non-supervised independent and blinded clustering of real clinical cases of DTT-BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered 'difficult to treat' into as many clusters they want (≤10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K-mean approach, and average silhouette method. RESULTS: There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT-BCCs into five clusters, easily recognized a posteriori as five clear-cut patterns of clinical situations. The concept of 'locally advanced' did not appear consistent between experts. CONCLUSION: Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT-BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology.

Position statement on classification of basal cell carcinomas. Part 2: EADO proposal for new operational staging system adapted to basal cell carcinomas.

BACKGROUND: No simple staging system has emerged for basal cell carcinomas (BCCs), since they do not follow the TNM process, and practitioners failed to agree on simple clinical or pathological criteria as a basis for a classification. Operational classification of BCCs is required for decision-making, trials and guidelines. Unsupervised clustering of real cases of difficult-to-treat BCCs (DTT-BCCs; part 1) has demonstrated that experts could blindly agree on a five groups classification of DTT-BCCs based on five patterns of clinical situations. OBJECTIVE: Using this five patterns to generate an operational and comprehensive classification of BCCs. METHOD: Testing practitioner's agreement, when using the five patterns classification to ensure that it is robust enough to be used in the practice. Generating the first version of a staging system of BCCs based on pattern recognition. RESULTS: Sixty-two physicians, including 48 practitioners and the 14 experts who participated in the generation of the five different patterns of DTT-BCCs, agreed on 90% of cases when classifying 199 DTT-BCCs cases using the five patterns classification (part 1) attesting that this classification is understandable and usable in practice. In order to cover the whole field of BCCs, these five groups of DTT-BCCs were added a group representing the huge number of easy-to-treat BCCs, for which sub-classification has little interest, and a group of very rare metastatic cases, resulting in a four-stage and seven-substage staging system of BCCs. CONCLUSION: A practical classification adapted to the specificities of BCCs is proposed. It is the first tumour classification based on pattern recognition of clinical situations, which proves to be consistent and usable. This EADO staging system version 1 will be improved step by step and tested as a decision tool and a prognostic instrument.

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

Not all melanomas are created equal: a review and call for more research into nodular melanoma.

Among the histogenic subtypes of melanoma, nodular melanoma (NM) is the major contributor for thicker and fatal melanomas and it has been associated with melanoma-specific death in thin tumours, highlighting an important subgroup of 'aggressive thin' melanomas. This review provides a synthesis of the distinct characteristics of NM, with respect to epidemiology and risk factors, clinical presentation, histopathology, molecular and dermoscopic aspects, and screening practices. The real challenges are to find better biomarkers of aggressiveness and to know whether the control of such aggressive melanomas can be influenced by targeted interventions such as early detection, drug interventions and preventive strategies.

Which adjuvant treatment for patients with BRAFV600-mutant cutaneous melanoma?

Treatment of patients with melanoma has considerably improved over the past decade and more recently with adjuvant therapies for patients with American Joint Committee on Cancer (AJCC) stage III (loco-regional metastases) or IV (distant metastases) totally resected melanoma, in order to prevent recurrence. In the adjuvant setting, two options are available to patients with BRAFV600-mutant AJCC stage III totally resected melanoma: anti-PD-1 blockers (nivolumab or pembrolizumab) or BRAF plus MEK inhibitors (dabrafenib plus trametinib). In the absence of comparative studies, it is difficult to determine which of these options is best. Our aim was to review published studies focusing on the management of patients with BRAFV600-mutant melanoma in the adjuvant setting. We also reviewed the main clinical trials of BRAF plus MEK inhibitors and immunotherapy in advanced (i.e. unresectable metastatic) BRAF-mutant melanoma in an attempt to identify results potentially affecting the management of patients on adjuvants. More adverse events are observed with targeted therapy, but all resolve rapidly upon drug discontinuation, whereas with immune checkpoint blockers some adverse events may persist. New therapeutic strategies are emerging, notably neoadjuvant therapies for stage III patients and adjuvant therapies for stage II patients; the place of the adjuvant strategy amidst all these options will soon be re-evaluated. The choice of adjuvant treatment could influence the choice of subsequent treatments in neo-adjuvant or metastatic settings. This review will lead clinicians to a better understanding of the different adjuvant treatments available for patients with totally resected AJCC stage III and IV BRAFV600-mutant melanoma before considering subsequent treatment strategies.

Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data☆.

BACKGROUND: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy. PATIENTS AND METHODS: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out. RESULTS: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI. CONCLUSION: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.

Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe. MATERIALS AND METHODS: A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P < 0.05. RESULTS: The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards. CONCLUSION: Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee.

The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee.

The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion.

Sonidegib and vismodegib are hedgehog pathway inhibitors (HhIs) approved for the treatment of advanced basal cell carcinoma (BCC). Until recently, vismodegib was the only targeted treatment available for patients with locally advanced BCC (laBCC) in cases where surgery and radiotherapy are inappropriate. Sonidegib has recently been approved and now presents an alternative treatment option. The clinical differences between the two HhIs in patients with laBCC are unclear, as no head-to-head randomized controlled trials are or will be initiated. Moreover, there were important differences in the designs of their pivotal studies, BOLT (sonidegib) and ERIVANCE (vismodegib), and these differences complicate evidence-based analysis of their relative efficacy and safety profiles. In this paper, a group of clinical experts in the management of laBCC summarizes the clinical and pharmacological profiles of sonidegib and vismodegib based on published data and their own clinical experience. One key difference between the two pivotal studies was the criteria used to assess BCC severity. ERIVANCE (a single-arm phase II trial) used the conventional Response Evaluation Criteria in Solid Tumors (RECIST), while the more recent double-blind randomized BOLT trial used the stringent modified RECIST. A preplanned analysis adjusted the outcomes from BOLT with RECIST-like criteria, and this enabled the experts to discuss relative efficacy outcomes for the two treatments. Centrally reviewed objective response rate (ORR) for vismodegib was 47.6% (95% CI: 35.5-60.6) at 21-month follow-up using RECIST. After adjusting with RECIST-like criteria, the ORR for sonidegib according to central review at 18-month follow-up was 60.6% (95% CI: 47.8-72.4). Both treatments were associated with similar patterns of adverse events. Sonidegib and vismodegib share the same efficacy and tolerability profiles, but their pharmacokinetic profiles show several differences, such as volume of distribution and half-life. Further studies are needed to understand how these differences may impact clinical practice.