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1.
Future Oncol ; : 1-10, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073799

RESUMEN

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC).Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles.Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue.Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue.Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.


Locally advanced basal cell carcinoma (laBCC) is a type of skin cancer that has the potential to invade surrounding tissues including bone, cartilage, nerve and muscle. Cemiplimab-rwlc is approved in the US for patients with laBCC following a therapy called hedgehog inhibitor (HHI) treatment or for whom HHIs are not appropriate. In a Phase II clinical trial, intravenous (in the vein) cemiplimab 350 mg every 3 weeks for up to nine treatment cycles resulted in clinically meaningful antitumor activity in patients with laBCC who progressed on or were intolerant to HHIs.This analysis evaluated health-related quality of life, symptom burden, emotions and functional status in these patients using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires. Baseline scores (scores at the start of the clinical trial) showed moderate to high levels of functioning and low symptom burden that, except for fatigue, were maintained or improved over the course of cemiplimab treatment. These results show that despite the presence of fatigue, health-related quality of life and functional status were maintained with cemiplimab across the study duration.

2.
Case Rep Dermatol ; 16(1): 173-180, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015399

RESUMEN

Introduction: Basal cell carcinoma (BCC) is treated with local surgery or noninvasive treatment modalities. If a BCC remains untreated, it can develop into a locally advanced BCC or a metastatic BCC. Case Presentation: Here we report in detail the management of three complex advanced BCC (aBCC) after treatment failure with vismodegib. On all tumors, next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed; subsequently, patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anticancer drugs based on the molecular tumor profile. All patients showed partial response or stable disease following treatment with second line PD-1 inhibitors with an average duration of response of 12.3 months. Discussion/Conclusion: Immunotherapy can be a treatment option for aBCC resistant to hedgehog pathway inhibitor treatment. However, despite the high tumor mutational burden of aBCCs, immunotherapy does not always lead to a long response. Rechallenge or combining treatment of hedgehog inhibitors and PD-1 inhibitors by parallel or alternating cycles may be a strategy to lengthen the treatment response.

3.
Cancer Lett ; 589: 216821, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38521198

RESUMEN

Basal cell carcinoma (BCC) is one of the most common human cancers. Most cases of BCC are amenable to surgical and topical treatments with excellent prognosis if diagnosed timely and managed appropriately. However, in a small percentage of cases, it could be locally advanced BBC (laBCC) and not amenable to surgery or radiation, including recurrent, large tumors or tumors that invade deeper tissue. Hedgehog inhibitors (vismodegib and sonidegib) are approved as the first-line treatment of laBCC. PD-1 inhibitor immunotherapy (cemiplimab) is indicated for cases that progressed on or could not tolerate hedgehog inhibitors or when hedgehog inhibitors are contraindicated. Given the modest response and bothersome side effects of some of the agents above, there are reports of novel treatments, and clinical trials are currently evaluating multiple agents.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/tratamiento farmacológico , Proteínas Hedgehog , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/inducido químicamente , Pronóstico , Antineoplásicos/efectos adversos , Anilidas/uso terapéutico , Anilidas/farmacología
5.
J Dermatol ; 51(1): 106-109, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37732421

RESUMEN

Basal cell carcinoma accounts for 75% of skin cancers worldwide and is the most common malignancy in Caucasians. Since chronic ultraviolet exposure is the major risk factor for its development, sun-exposed areas such as the face are frequently affected. The gold-standard treatment is surgical excision. Radiotherapy may be considered in selected cases such as unresectable primary tumors. In some patients, when the risk of a significant functional/cosmetic deficit advises against both surgery and radiotherapy, target therapy (hedgehog pathway inhibitors) can be administered alone or in a neoadjuvant setting, to reduce the tumor size and make it eligible for surgery. Vismodegib as a neoadjuvant treatment before surgery has been investigated in a single, multicentre, open-label, phase II trial (VISMONEO); however, sonidegib has not yet been evaluated in this setting. We report the cases of two patients with locally advanced basal cell carcinoma of the face who achieved complete remission with sonidegib followed by a more limited surgical excision than would have been needed without target therapy.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Proteínas Hedgehog/metabolismo , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/cirugía , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugía , Compuestos de Bifenilo/uso terapéutico , Compuestos de Bifenilo/efectos adversos , Antineoplásicos/efectos adversos , Respuesta Patológica Completa
6.
Cancers (Basel) ; 15(14)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37509282

RESUMEN

Basal cell carcinoma (BCC) represents the most common skin cancer and locally advanced BCC (laBCC) refers to an aggressive, large, infiltrative BCC that cannot be treated by surgery or radiotherapy. Sonidegib is a Hedghehog inhibitor (HHi) indicated for laBCC. This is a monocentric retrospective real-life study of laBCCs receiving Sonidegib treatment. Although Sonidegib is widely used, since its approval by Food and Drug Administration in 2015, only a limited number of real-life experiences have been reported. Eleven patients, including four patients diagnosed with Basal Cell Naevus syndrome, received treatment with Sonidegib for laBCCs. Seven (63.6%) patients experienced adverse events (AEs) but only three had to discontinue treatment and were therefore excluded from the following results. Four patients (50%) achieved complete clinical remission (CR); in all cases the remission was confirmed by biopsy. Partial response (PR) was found in three patients out of eight (37.5%). One patient out of eight (12.5%) showed a steady disease (SD). None of the patients showed signs of progression during treatment with HHi. Sonidegib showed the same efficacy in treating laBCCs as already seen in trials. All four patients suffering from Basal Cell Naevus syndrome achieved disease control by being treated with Sonidegib. Consequently, we strongly advise the joint management of laBCCs through a multidisciplinary team whenever feasible.

7.
Artículo en Inglés | MEDLINE | ID: mdl-37239551

RESUMEN

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer and can represent a therapeutic challenge in patients with locally advanced disease. Vismodegib is a hedgehog pathway inhibitor approved by the FDA for use in this type of tumor. We present a case series to describe our experience with the use of vismodegib. METHODS: A retrospective study that included patients treated with vismodegib at our dermatology unit was conducted. Monthly follow-up was performed, and we registered the clinical evolution and adverse reactions. RESULTS: A total of six patients with locally advanced BCCs were included (50% males and 50% females), with a mean age of 78.5 years old. The treatment was administered over a mean of 5 months. A complete response was observed in four cases and partial response in two cases. No recurrence was detected, with a median follow-up duration after discontinuation of 18 months. Most patients (83%) had at least one adverse event, and two needed dose adjustment temporarily or permanently to continue. The main adverse effect was muscle spasms (66.7%). The main limitation of our study was the small sample, which was not representative of the general population. CONCLUSIONS: Vismodegib is a safe and effective treatment for locally advanced BCC, and its role in unresectable BCC seems to be an important option in these challenging cases.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Masculino , Femenino , Humanos , Anciano , Estudios Retrospectivos , Proteínas Hedgehog , Carcinoma Basocelular/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inducido químicamente , Antineoplásicos/efectos adversos
8.
Eur J Cancer ; 177: 103-111, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36335780

RESUMEN

BACKGROUND: Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived. METHODS: This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%). RESULTS: Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction). CONCLUSION: Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/patología , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapéutico , Inmunoterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Cutáneas/patología
9.
J Clin Aesthet Dermatol ; 15(7): 24-25, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35942013

RESUMEN

Background: Advanced nonmelanoma skin cancer (NMSC) is a sometimes unrecognized public health burden. The development of immune checkpoint inhibitors (ICIs), such as those affecting programmed cell death protein-1 (PD-1), have dramatically changed the management of advanced NMSC. Dermatologists need to be knowledgeable about these therapies given their key role in diagnosing, treating, and comanaging NMSC. The purpose of this study was to assess the knowledge base and identify knowledge gaps that dermatologists may have regarding ICIs and assess advanced NMSC referral patterns. Methods: A 10-question survey was emailed to United States-based dermatologists in July 2021 assessing knowledge of ICI therapy and referral patterns for metastatic cutaneous squamous cell carcinoma (mcSCC) or locally advanced basal cell carcinoma (laBCC) management. Results: At their current knowledge level, respondents averaged 40.6 out of 100 (95% CI [35.1, 46.0]) when asked how comfortable they feel counseling a patient on the risks and benefits of an ICI. Seventy-one percent reported that having more information about treatment for mcSCC or laBCC would be helpful in their practice. Being in practice for less than 10 years was not significantly associated with desiring more information about treatment. The respondents reported that the highest number of annual average referrals out for mcSCC or laBCC were made to Mohs surgeons. Fifty-four percent of respondents received referrals for mcSCC or laBCC, and of the providers receiving referrals, 40 percent of them came from general dermatology. Conclusion: These results demonstrate that a knowledge gap exists for dermatologists in treating mcSCC and laBCC with immunotherapy. There is a need among all dermatologists, regardless of years in practice, to receive this information.

10.
Drugs Context ; 112022.
Artículo en Inglés | MEDLINE | ID: mdl-35912002

RESUMEN

Background: Sonidegib and vismodegib are Hedgehog pathway inhibitors (HhIs) that play a relevant role in the management of locally advanced basal cell carcinoma (laBCC). This study compared the efficacy and safety of both HhIs based on their available data using effect size measures such as number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Methods: We reviewed data from pivotal trials of sonidegib (BOLT) and vismodegib (ERIVANCE). The NNT for sonidegib and vismodegib was calculated from objective response rate (ORR) values. The NNH was calculated from data relating to treatment discontinuation due to adverse events (AEs) and incidence of AEs. The LHH was calculated as the ratio between the corresponding NNH and NNT. Results: For sonidegib (200 mg), the NNT for ORR at 18 months was 1.65 (95% CI 1.35-2.01) whilst that for vismodegib (150 mg) at 21 months was 2.10 (95% CI 1.65-2.82). The NNH related to treatment discontinuation due to AEs was 1.9 (95% CI 1.6-2.5) for sonidegib and 1.8 (95% CI 1.4-2.2) for vismodegib. The LHH for sonidegib and vismodegib related to treatment discontinuation due to AEs was 1.14 and 0.84, respectively, whilst the LHH according to AEs of grade ≥3 was 1.41 for sonidegib and 0.85 for vismodegib. Conclusions: Sonidegib showed a better benefit-risk ratio compared to vismodegib, being more likely to achieve therapeutic response than to AEs leading to discontinuation. These results should be confirmed in clinical practice and/or in a direct comparison study.

11.
Drugs Context ; 112022.
Artículo en Inglés | MEDLINE | ID: mdl-35677182

RESUMEN

Sonidegib is a Hedgehog signalling pathway inhibitor approved for use in patients with advanced basal cell carcinoma (BCC) not eligible for surgery or radiotherapy. This report describes clinical experience with sonidegib in two patients with locally advanced BCC (one with a tumour adjacent to the right eye and the other with a tumour associated with the left ear) and in one patient with Gorlin syndrome. Two of the patients had recurrent and intractable tumours. Treatment with sonidegib 200 mg/day led to remission in both patients with locally advanced BCC within 7 months and to a reduction in the size and number of lesions after 4 months in the patient with Gorlin syndrome. Adverse effects reported in these patients were cramps, alopecia, ageusia and weight loss, all of which were mild and consistent with the known toxicity profile for sonidegib. Sonidegib has an important role to play in the effective treatment of challenging cases of advanced BCC. In parallel, a need remains to improve management protocols for patients with advanced BCC, particularly through earlier intervention and a multidisciplinary team approach.

12.
Actas Dermosifiliogr ; 113(5): 443-450, 2022 May.
Artículo en Inglés, Español | MEDLINE | ID: mdl-35697404

RESUMEN

As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Compuestos de Bifenilo , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapéutico , Humanos , Piridinas , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología
13.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(5): 443-450, Mayo 2022. ilus, tab
Artículo en Español | IBECS | ID: ibc-206483

RESUMEN

El carcinoma de células basales (CBC) es una de las neoplasias malignas más frecuentes, por lo que se ha convertido en una importante carga asistencial. Su incidencia se incrementa anualmente, especialmente en la población con mayor edad. A pesar de que generalmente está bien localizado, el CBC tiene la capacidad de destruir tejidos y evolucionar a un CBC localmente avanzado (CBCla) o incluso, aunque de forma más rara, a un CBC metastásico (CBCm). Las opciones terapéuticas convencionales en estos casos están bien establecidas, entre las cuales se incluyen la cirugía y la radioterapia. Sin embargo, no todos los casos son elegibles para realizar un tratamiento de tipo convencional. Recientemente, los tratamientos biológicos vienen ganando una mayor atención y son objeto de diversos estudios de investigación. De este modo se ha desarrollado una terapia dirigida utilizando los inhibidores de la vía de Hedgehog (IVH), teniendo en cuenta que se trata de una vía patogénica clave tanto en el CBCla como en el CBCm. En la actualidad, para poder tratar el CBCla y el CBCm no operables existen dos IVH aprobados: el vismodegib y el sonidegib. Esta revisión busca explorar la fisiopatología de la vía del Hedgehog responsable del desarrollo del CBC y hacer una actualización en cuanto a la eficacia, así como de las propiedades farmacocinéticas de los IVH, características que los convirtieron en la opción terapéutica ideal en el CBCla o en el CBCm, ya sea en forma de monoterapia o en combinación con alguno de los tratamientos convencionales (AU)


As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies (AU)


Asunto(s)
Humanos , Antineoplásicos/uso terapéutico , Neoplasias Basocelulares/tratamiento farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Basocelulares/fisiopatología , Neoplasias Cutáneas/fisiopatología
14.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(5): t443-t450, Mayo 2022. ilus, tab
Artículo en Inglés | IBECS | ID: ibc-206484

RESUMEN

As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies (AU)


El carcinoma de células basales (CBC) es una de las neoplasias malignas más frecuentes, por lo que se ha convertido en una importante carga asistencial. Su incidencia se incrementa anualmente, especialmente en la población con mayor edad. A pesar de que generalmente está bien localizado, el CBC tiene la capacidad de destruir tejidos y evolucionar a un CBC localmente avanzado (CBCla) o incluso, aunque de forma más rara, a un CBC metastásico (CBCm). Las opciones terapéuticas convencionales en estos casos están bien establecidas, entre las cuales se incluyen la cirugía y la radioterapia. Sin embargo, no todos los casos son elegibles para realizar un tratamiento de tipo convencional. Recientemente, los tratamientos biológicos vienen ganando una mayor atención y son objeto de diversos estudios de investigación. De este modo se ha desarrollado una terapia dirigida utilizando los inhibidores de la vía de Hedgehog (IVH), teniendo en cuenta que se trata de una vía patogénica clave tanto en el CBCla como en el CBCm. En la actualidad, para poder tratar el CBCla y el CBCm no operables existen dos IVH aprobados: el vismodegib y el sonidegib. Esta revisión busca explorar la fisiopatología de la vía del Hedgehog responsable del desarrollo del CBC y hacer una actualización en cuanto a la eficacia, así como de las propiedades farmacocinéticas de los IVH, características que los convirtieron en la opción terapéutica ideal en el CBCla o en el CBCm, ya sea en forma de monoterapia o en combinación con alguno de los tratamientos convencionales (AU)


Asunto(s)
Humanos , Antineoplásicos/uso terapéutico , Neoplasias Basocelulares/tratamiento farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Basocelulares/fisiopatología , Neoplasias Cutáneas/fisiopatología
15.
Dermatol Ther ; 35(6): e15441, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35279921

RESUMEN

In recent years, the category of hedgehog pathway inhibitor (HHI) has shown great results in patients with advanced basal cell carcinoma (aBCC), but few real-life data on efficacy and safety profile of sonidegib are available. We report our management of locally advanced BCCs (laBCCs) with sonidegib, also describing the favorable response of locally advanced basosquamous carcinomas (laBSCs) treated with this hedgehog signaling inhibitor. Sonidegib was generally well tolerated and it achieved high response rates, improving quality of life. Our single-center experience could be useful to better delineate long-term efficacy and tolerability profile demonstrated in the trials described in literature. Moreover, our cases provide preliminary evidence that sonidegib might be effective for laBSC.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Antineoplásicos/efectos adversos , Compuestos de Bifenilo , Carcinoma Basocelular/patología , Proteínas Hedgehog/uso terapéutico , Humanos , Piridinas , Calidad de Vida , Neoplasias Cutáneas/patología
16.
Expert Rev Anticancer Ther ; 22(3): 243-248, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35175882

RESUMEN

INTRODUCTION: Locally advanced basal cell carcinoma (laBCC) represents approximatively 1% of all BCCs. Metastatic BCC (mBCC) is even more rare. Most cases are observed in immunocompromised patients, particularly solid organ transplant recipients (OTRs). When surgery and/or radiation therapy for laBCC or mBCC is not reasonable, oral hedgehog inhibitor (HHI) therapy may be initiated. LaBCC or mBCC patients with primary or secondary resistance, progression or intolerance to HHIs could benefit from programmed cell death protein-1 (PD-1) inhibitors as this has recently been published for cemiplimab, a recombinant IgG4 human monoclonal antibody anti-PD-1 for the intravenous treatment of laBCC and mBCC. AREAS COVERED: Principal studies evaluating the efficacy and safety of cemiplimab for laBCC and mBCC are presented and discussed. EXPERT OPINION: Cemiplimab is the first FDA (2021) approved anti-PD-1 antagonist for the systemic treatment of laBCC and mBCC which had previously shown disease progression on or intolerance to HHIs. Experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is associated with a risk of organ graft rejection, advantages and disadvantages should be evaluated for every individual OTR patient with laBCC or mBCC, eligible for cemiplimab therapy.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados , Antineoplásicos/efectos adversos , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Proteínas Hedgehog , Humanos , Piridinas/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología
17.
Photodiagnosis Photodyn Ther ; 36: 102553, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34597833

RESUMEN

Locally advanced basal cell carcinoma (laBCC) is an uncommon cutaneous malignant tumor characterized by direct spread and extensive tissue destruction. The optimal therapy for laBCC remains a challenge, especially for elderly patients. Photodynamic therapy (PDT) has its advantage of better tumor selectivity, providing focal treatment for various non-melanoma carcinomas. We report that a new combination treatment of HiPorfin-photodynamic therapy (HiPorfin-PDT) and modified topical 5-aminolevulinic acid-photodynamic therapy (ALA-PDT), named bimodal PDT was successful to treat a 91-year-old patient with laBCC. As for side effects, hypertrophic scar and pain were observed. The symptoms were relieved after intralesional corticosteroid, 980 nm laser and 595 nm pulsed dye laser treatment in 3 months.


Asunto(s)
Carcinoma Basocelular , Fotoquimioterapia , Neoplasias Cutáneas , Anciano , Anciano de 80 o más Años , Ácido Aminolevulínico/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Cicatriz/tratamiento farmacológico , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico
18.
EClinicalMedicine ; 35: 100844, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33997740

RESUMEN

BACKGROUND: Surgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC. METHODS: VISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery. FINDINGS: 55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51). INTERPRETATION: Neoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. FUNDING: VISMONEO was funded by F. Hoffmann-La Roche Ltd.

19.
Actas Dermosifiliogr (Engl Ed) ; 112(4): 295-301, 2021 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-33197438

RESUMEN

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Antineoplásicos/efectos adversos , Compuestos de Bifenilo , Carcinoma Basocelular/tratamiento farmacológico , Proteínas Hedgehog/uso terapéutico , Humanos , Piridinas , Neoplasias Cutáneas/tratamiento farmacológico
20.
Acta Chir Belg ; 121(3): 198-203, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31437079

RESUMEN

BACKGROUND: Since the introduction of Vismodegib as treatment of recurrent locally advanced basal cell carcinoma (laBCC), clinicians are faced with new dilemmas: 'Can Vismodegib replace complex reconstructions?', 'What is the role of neoadjuvant use of Vismodegib?' and 'What is the best approach in case of complete clinical remission after Vismodegib in a neoadjuvant setting?' METHODS: Case report and literature review. RESULTS: Case report Complete dermoscopic remission after eight months Vismodegib was obtained in a patient with recurrent laBCC. Follow-up was 12 months. Literature review: Vismodegib shows histologic clearance in 42% of patients with operable basal cell carcinoma. Recurrence after neoadjuvant use of Vismodegib in laBCC was described. Moreover, histology revealed residual tumour cells in cases of complete clinical remission after 6 months Vismodegib. CONCLUSIONS: Vismodegib cannot replace complex reconstructions. However, in unresectable laBCC, Vismodegib can provide a bridge to surgery. Due to the possibility of persistent tumour cells, we recommend imaging-assisted surgery and an imaging-based follow-up. In case of complete clinical remission after Vismodegib in a neoadjuvant setting, we recommend that Vismodegib be continued as long as the adverse effects are tolerated and an imaging-based follow-up is advised.


Asunto(s)
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutáneas , Anilidas , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia , Piridinas , Neoplasias Cutáneas/tratamiento farmacológico
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