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Conference summaries


Non-melanoma skin cancer

Systemic treatments of non-melanoma skin cancer

Presented by: Prof. Henrik F. Lorentzen Department of Dermatology, Aarhus University Hospital, Denmark
  • New treatments are increasing the range of options available to manage both BCC and SCC.
  • These include vismodegib and sonidegib for BCC and cemiplimab for cutaneous SCC.

Keratinocyte cancers–basal and cutaneous squamous cell carcinoma (BCC, cSCC)–are the most common forms of non-melanoma skin cancer and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. Pathobiologically, activation of the Hedgehog (HH) signalling pathway has been shown to play a critical role in the majority of cases and is recognised as a valid therapeutic target. As such, hedgehog pathway inhibitors such as vismodegib and sonidegib are being investigated in high-risk cancers.

  • Vismodegib is a small-molecule inhibitor of smoothened (SMO), a key component of the hedgehog signalling pathway that has been studied in BCC patients after failure of surgery and radiotherapy treatments. [1]
  • Vismodegib has become an established treatment option for patients with advanced BCC in clinical practice.
  • However, certain limitations of treatment with vismodegib should be kept in mind.
  • Side effects lead to a significant rate of treatment discontinuation, thereby limiting overall drug exposure.
  • Accordingly, continuous long-term treatment with vismodegib is not feasible in most patients.
  • Clinical end points which may help to determine the optimal treatment duration (lifelong/continuous treatment vs treatment until best response) are lacking.
  • Alternative dosing regimens may improve tolerability and dose exposure, but more studies are needed to optimise the dosing regimen. [2]
  • Muscle cramps are an important side effect of vismodegib, but may be reduced with the administration of L-carnitine, based on a case report. [3]
  • Other side effects include decreased sense of taste, hair loss, loss of appetite, weight loss and fatigue, as well as severe birth defects.
  • Of note, it has been reported that in advanced BCC, patients who are resistant to treatment with vismodegib are also resistant to sonidegib. [4]
  • Cemiplimab is a new anti-PD1 checkpoint inhibitor antagonist that is under development for SCC.
  • Anti-PD1 agents are well known from their role in melanoma immunotherapy.
  • PD-1 is a relevant target in cancer as malignant cells may develop a ligand towards the PD-1 receptor that allows them to avoid attack by cytotoxic T-cells.
  • In addition to melanoma, SCC is another tumour type in which alterations in PD-1 are frequently found.
  • The effects of PD-1 blockade with cemiplimab have been recently studied in advanced cutaneous SCC. [5]
  • Response to cemiplimab was observed in 13 of 26 patients (50%; 95% CI, 30-70).
  • In the metastatic-disease cohort of the phase II study, a response was observed in 28 of 59 patients (47%; 95% CI, 34-61).
  • Among the 28 patients showing a response, duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at end of study.
  • In a follow-up study of the same trial, estimated 1-year progression-free survival (PFS) was 53% and median PFS was 18.4 months.
  • Adverse events include diarrhoea, fatigue, nausea, constipation and rash.
  • Based on these results, cemiplimab has been approved by both the FDA and EMA for metastatic cutaneous SCC.
  • Vismodegib and sonidegib are showing promise in treatment of BCC.
  • Cemiplimab is a new treatment for SCC that was recently approved in Europe and the USA.

Key messages/Clinical perspectives

  • New treatments are increasing the range of options available to manage both BCC and SCC.


References

References


  1. Sekulic A, Migden MR2, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017 May 16;17(1):332.
  2. Dréno B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):404-12.
  3. Dinehart MS, McMurray, S, Dinehart S, et al. L-Carnitine reduces muscle cramps in patients taking vismodegib. Skin. 2018;2:2.
  4. Danial C, Sarin KY, Oro AE, et al. An investigator-initiated open-label trial of sonidegib in advanced basal cell carcinoma patients resistant to vismodegib. Clin Cancer Res. 2016 Mar 15;22(6):1325-9.
  5. Migden MR, Rischin D, Schmults CD,et al. PD-1 Blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-51.

Presenter disclosure information: HF Lorentzen: None disclosed.

Medical writer: Patrick Moore, PhD

Reviewer: Martina Lambertini, MD

Local reviewers: Martina Lambertini, MD (Italian); Alain Brassard, MD (French); Jorge Moreno González, MD (Spanish); Swen Malte John, MD, PhD (German); Marcelo Arnone, MD (Portuguese)

Scientific Editor: Prof. Brigitte Dréno, MD


CLINICAL TRIALS

PSORIASIS

Efficacy and safety of ixekizumab in a phase 3, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis

Presented by: Prof. Kim A. Papp, Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Canada

ATOPIC DERMATITIS

Efficacy and safety of baricitinib in combination with topical corticosteroids in moderate to severe atopic dermatitis: results of a phase 3 randomized, double-blind, placebo-controlled 16-week trial (BREEZE-AD7)

Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany

PRURIGO NODULARIS

Phase 2b study of nemolizumab in patients with moderate to severe prurigo nodularis and associated severe pruritus

Presented by: Prof. Sonja Ständer, Department of Dermatology and Center for Chronic Pruritus (KCP), University Hospital Münster, Germany

VITILIGO

Efficacy and safety of a 52-week, randomized, double-blind trial of ruxolitinib cream for the treatment of vitiligo

Presented by: Dr. Amit G. Pandya, University of Texas Southwestern Medical Center, Dallas, TX, USA
 

EMERGING TERAPIES

PSORIASIS

Emerging therapies for psoriasis

Presented by: Prof. Michel Gilliet, Department of Dermatology, Lausanne CHUV, Switzerland

ATOPIC DERMATITIS

New and emerging therapies in atopic dermatitis

Presented by: Prof. Dagmar Simon, Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland

ONYCHOMYCOSIS

Emerging treatments for onychomycosis

Presented by: Dr. Ditte Marie L. Saunte, Department of Dermatology, Institute for Clinical Medicine, Zealand University Hospital, Roskilde, Denmark
 

REVIEW & UPDATES

ACNE & ROSACEA

Isotretinoin for acne and rosacea

Presented by: Dr. Pedro Mendes-Bastos, Dermatology Centre, Hospital CUF Descobertas, Lisbon, Portugal

ALOPECIA AREATA

New drugs for alopecia areata

Presented by: Prof. Spyridon Gkalpakiotis, Department of Dermatovenereology, Third Faculty of Medicine and University Hospital of Kralovske Vinohrady, Prague, Czech Republic.

DERMATOSURGERY

Update in dermatosurgery

Presented by: Prof. Eduardo Nagore, Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain

EPIDERMOLYSIS BULLOSA

New start of gene therapy in epidermolysis bullosa

Presented by: Prof. Leena K. Bruckner-Tuderman, University Medical Center, Albert-Ludwigs-University of Freiburg, Germany

MELANOMA

Treatment resistance in metastatic melanoma

Presented by: Prof. Martin Röcken, Department of Dermatology, Eberhard-Karls-University Tübingen, Germany

SCAR TREATMENT

Future of medical scar treatment

Presented by: Prof. Gabriella Fabbrocini, Department of Dermatology, University of Naples Federico II, Naples, Italy
 

EDUCATION FORUM

NON-MELANOMA SKIN CANCER

Systemic treatments of non-melanoma skin cancer

Presented by: Prof. Henrik F. Lorentzen, Department of Dermatology, Aarhus University Hospital, Denmark
 

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