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1.
J Surg Oncol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33289125

RESUMO

BACKGROUND AND OBJECTIVES: Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations. METHODS: An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking. RESULTS: Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations. CONCLUSIONS: Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.

3.
Cancer Control ; 27(1): 1073274820983019, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33372814

RESUMO

Patients with unresectable hepatic metastases, from uveal or ocular melanoma, are challenging to treat with an overall poor prognosis. Although over the past decade significant advances in systemic therapies have been made, metastatic disease to the liver, especially from uveal melanoma, continues to be a poor prognosis. Percutaneous hepatic perfusion (PHP) is a safe, viable treatment option for these patients. PHP utilizes high dose chemotherapy delivered directly to the liver while minimizing systemic exposure and can be repeated up to 6 times. Isolation of the hepatic vasculature with a double-balloon catheter allows for high concentration cytotoxic therapy to be administered with minimal systemic adverse effects. A detailed description of the multidisciplinary treatment protocol used at an institution with over 12 years of experience is discussed and recommendations are given. A dedicated team of a surgical or medical oncology, interventional radiology, anesthesiology and a perfusionist allows PHP to be repeatedly performed as a safe treatment strategy for unresectable hepatic metastases.

4.
Ann Surg Oncol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230747

RESUMO

BACKGROUND: Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. PATIENTS AND METHODS: Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. RESULTS: Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). CONCLUSIONS: In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

5.
Ann Surg Oncol ; 27(13): 5107-5118, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918177

RESUMO

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). METHODS: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. RESULTS: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). CONCLUSIONS: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

7.
Eur J Surg Oncol ; 46(11): 2140-2146, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32739218

RESUMO

INTRODUCTION: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. METHODS: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. RESULTS: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. CONCLUSION: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.

8.
Melanoma Manag ; 7(2): MMT41, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32821373

RESUMO

Aim: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization. Materials & methods: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions. Results: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing. Conclusion: In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.

9.
Expert Rev Anticancer Ther ; 20(8): 687-701, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32667249

RESUMO

INTRODUCTION: Mitogen-activated protein kinase (MAPK) signal transduction pathway inhibition through the use of agents binding to signal cascade kinases BRAF and MEK has become a key treatment strategy of patients with BRAF-mutant, unresectable melanoma. AREAS COVERED: Detailed analysis is undertaken of the current data, presenting the efficacy and safety of recently developed therapies targeting BRAF and MEK inhibition in the setting of unresectable melanoma. MAPK signal transduction, translational findings, current phase I, II and III clinical trials, and ongoing studies are explored, including use of MAPK pathway inhibition in the neoadjuvant and adjuvant settings as well as in combination with immunotherapy and other therapies. EXPERT OPINION: Inhibition of the MAPK pathway significantly improves response, progression-free survival, disease specific survival, and overall survival for patients with BRAF-mutant, unresectable melanoma. The concurrent administration of BRAF and MEK inhibiting agents improves response rate and outcomes and reduces serious adverse effects, including development of new cutaneous malignancies. Triplet therapy with BRAK/MEK combination and immunotherapy has shown in early results to increase duration of response and may be best used sequentially as opposed to concurrently to avoid treatment limiting toxicities. Current clinical trials will further define these therapies and their impact on treatment of melanoma.

10.
Surgery ; 168(3): 518-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32669204

RESUMO

BACKGROUND: It is unknown whether all thick melanomas share the same prognostic features. We present a large, multi-institutional study on thick melanoma, evaluating for factors prognostic of survival. METHODS: We queried the database of the Sentinel Lymph Node Working Group for patients with thick melanoma (>4 mm) who had a sentinel lymph node biopsy from 1993 to 2018. Clinicopathologic characteristics were correlated with overall survival. RESULTS: There were 1,235 patients with a median follow-up of 28 months. Median thickness was 5.9 mm, with 713, 356, and 166 cases having a thickness of >4 to 6, >6 to 10, and >10 mm, respectively. Ulceration was seen in 51.2% of cases, while sentinel lymph node metastases were seen in 439 of 1,235 (35.5%) cases. For melanomas >4 to 6 mm, age, thickness, ulceration, lymphovascular invasion, and sentinel lymph node metastasis were correlated with overall survival (all P < .05), but for melanomas >6 to 10 mm, only sex and sentinel lymph node metastasis were prognostic of overall survival (both P < .05). For melanomas >10 mm, only sentinel lymph node metastasis predicted overall survival on multivariable analyses (P < .05). CONCLUSION: Prognostic markers of overall survival for thick melanoma include thickness, ulceration, and sentinel lymph node metastasis, but also include other unique factors such as lymphovascular invasion. Moreover, certain prognostic markers for survival are associated with different subgroups of thick melanoma, which vary based on thickness group.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , Melanoma/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/mortalidade , Pele/patologia , Idoso , Vasos Sanguíneos/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga Tumoral
12.
Ann Surg Oncol ; 27(13): 5259-5266, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32529271

RESUMO

PURPOSE: We hypothesized that initial biopsy may understage acral lentiginous melanoma (ALM) and lead to undertreatment or incomplete staging. Understanding this possibility can potentially aid surgical planning and improve primary tumor staging. METHODS: A retrospective review of primary ALMs treated from 2000 to 2017 in the US Melanoma Consortium database was performed. We reviewed pathology characteristics of initial biopsy, final excision specimens, surgical margins, and sentinel lymph node biopsy (SLNB). RESULTS: We identified 418 primary ALMs (321 plantar, 34 palmar, 63 subungual) with initial biopsy and final pathology results. Median final thickness was 1.8 mm (range 0.0-19.0). There was a discrepancy between initial biopsy and final pathology thickness in 180 (43%) patients with a median difference of 1.6 mm (range 0.1-16.4). Final T category was increased in 132 patients (32%), including 47% of initially in situ, 32% of T1, 39% of T2, and 28% of T3 lesions. T category was more likely to be increased in subungual (46%) and palmar (38%) melanomas than plantar (28%, p = 0.01). Among patients upstaged to T2 or higher, 71% had ≤ 1-cm margins taken. Among the 27 patients upstaged to T1b or higher, 8 (30%) did not have a SLNB performed, resulting in incomplete initial staging. CONCLUSIONS: In this large series of ALMs, final T category was frequently increased on final pathology. A high index of suspicion is necessary for lesions initially in situ or T1 and consideration should be given to performing additional punch biopsies, wider margin excisions, and/or SLNB.

13.
Ann Surg Oncol ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524460

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. PATIENTS AND METHODS: The Sentinel Lymph Node Working Group database was queried for thick (> 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). RESULTS: There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P < 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas > 4-8 mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P < 0.0001). For melanomas > 8 mm, only SLN metastasis significantly predicted MSS (> 8-12 mm: HR 3.93, 95% CI 2.00-7.73, P < 0.0001; > 12 mm: HR 3.58, 95% CI 1.56-8.22, p < 0.0027). CONCLUSIONS: Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

14.
Ann Surg Oncol ; 27(5): 1420-1429, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32152775

RESUMO

BACKGROUND: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

15.
J Surg Oncol ; 122(1): 99-105, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32162353

RESUMO

Patients with unresectable cutaneous and soft tissue malignancies confined to a limb have many treatment options. Isolated limb infusion (ILI) is one therapeutic option whereby the extremity is isolated and perfused with high-dose chemotherapy through a percutaneously placed catheter-based procedure. A detailed description of the ILI protocol at the Moffitt Cancer Center is given. We have shown that ILI is a safe and effective treatment strategy for malignancies confined to an extremity.


Assuntos
Antineoplásicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/métodos , Melanoma/tratamento farmacológico , Sarcoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Quimioterapia do Câncer por Perfusão Regional/educação , Extremidades/irrigação sanguínea , Extremidades/patologia , Humanos , Curva de Aprendizado
17.
Ann Surg Oncol ; 27(1): 196-202, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30949862

RESUMO

BACKGROUND: Robotic pelvic lymphadenectomy (rPLND) has been demonstrated to be a safe and effective minimally invasive approach for patients with metastatic melanoma to the iliac nodes. However, the long-term oncologic benefit of this procedure remains poorly defined. METHODS: A single-institutional study comparing perioperative outcomes and survival [recurrence-free (RFS) and overall survival (OS)] between rPLND and open PLND (oPLND) for metastatic melanoma was conducted. RESULTS: From 2006 to 2018, a total of 63 PLND cases were identified: 22 rPLND and 41 oPLND. Evidence of isolated pelvic metastasis was the most common indication for PLND in both groups (rPLND: 64%, oPLND: 85%). There was no difference in median pelvic lymph node yield (11 vs. 9 nodes, p = 0.65). Neither treatment group experienced a Clavien-Dindo complication ≥ 3. rPLND was associated with a shorter length of stay compared with oPLND (2 vs. 4 days, p < 0.001). With a median follow-up of 37 months, there was no difference in RFS (14.4 vs. 9.6 months, p = 0.47) and OS (43 vs. 50 months, p = 0.58) between rPLND and oPLND, respectively. In basin recurrence was low with 1 (4.5%) and 3 (7.3%) patients in the rPLND and oPLND cohorts, respectively, experiencing an event (p = 0.9). CONCLUSIONS: rPLND for metastatic melanoma is a safe, minimally invasive treatment strategy that appears to result in similar intermediate term recurrence and survival rates as oPLND but shorter hospital stays.


Assuntos
Excisão de Linfonodo , Melanoma/secundário , Melanoma/cirurgia , Procedimentos Cirúrgicos Robóticos , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Tempo de Internação , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Pelve/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
18.
Pathol Oncol Res ; 26(1): 239-244, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29948620

RESUMO

Cutaneous adnexal malignancies are biologically and pathologically diverse, and associated with a range of clinical outcomes. Given their rarity, the prognosis and optimal treatment of these neoplasms remains unclear. A single institution database from a tertiary care cancer center of patients treated for malignant cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic variables and outcome measures were analyzed in patients undergoing wide excision with or without sentinel node biopsy. 103 patients were analyzed; the majority of tumors were of eccrine sweat gland derivation (n = 69, 70%), and these exhibited a higher rate of nodal involvement and overall worse outcome. Sixteen patients (16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease at presentation and 6 who developed nodal metastasis during followup. 20 patients underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of nodal metastases occurred in patients with porocarcinoma. Seven patients died of disease (7%) with a median time from diagnosis to death of 48 months (range, 10-174). After a median follow up of 44.7 months, age > 70 years and larger tumor size were significantly associated with worse overall survival. Adnexal malignancies are rare tumors, and there is a paucity of information to guide the clinician in determining optimum surgical and medical treatment. Tumors of eccrine derivation, especially porocarcinomas, have a high risk of nodal involvement and may be considered for sentinel node biopsy.

19.
Expert Opin Biol Ther ; 20(1): 9-14, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31690129

RESUMO

Introduction: Intralesional therapies have emerged as effective immune therapies for locally advanced and metastatic melanoma. Talimogene laherparepvec (T-VEC), an oncolytic virus derived from the herpes simplex 1 (HSV-1) virus, is the first and only FDA approved intralesional therapy for recurrent, unresectable cutaneous, subcutaneous or nodal metastases from melanoma.Areas covered: We discuss results from clinical trials of T-VEC including data on safety, biodistribution, and viral shedding, which established the current treatment protocol and basis for FDA approval. Data are presented from early implementation of T-VEC in clinical practice. We explore the use of T-VEC in the neoadjuvant setting and in combination with anti-CTLA-4 and PD-1 therapies, including available evidence to support a mechanism for the observed synergistic effect.Expert opinion: Intralesional T-VEC is effective for unresectable stage III and IVa melanoma, with early clinical results comparing favorably to response rates from clinical trials. Clinical applications will likely increase as more data become available on its use in the neoadjuvant setting and in combination with other systemic immune therapies. We expect the fields of intralesional therapy and viral oncotherapy to expand as we better understand how to manipulate the tumor microenvironment and host immune response to cancer.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Melanoma/terapia , Herpesvirus Humano 1 , Humanos , Terapia Neoadjuvante , Terapia Viral Oncolítica , Vírus Oncolíticos , Distribuição Tecidual
20.
Expert Opin Pharmacother ; 21(2): 155-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31790307

RESUMO

Introduction: In the treatment of advanced BRAF-mutant melanoma, selective regulation of the MAPK pathway with BRAF and MEK inhibition has emerged as one of the mainstays of therapy.Areas covered: The authors present the current data on encorafenib as a compound, its pharmacokinetic and pharmacodynamics properties. This review includes current data on encorafenib therapy as a single agent as well as in combination with the MEK-inhibitor binimetinib and other systemic therapies.Expert opinion: BRAF inhibition with encorafenib exhibits substantial antitumor activity with less paradoxical MAPK pathway activation leading to treatment resistance. Combination therapy with MEK inhibitors improves response rate, progression-free survival, and overall survival in patients with BRAF-mutant metastatic melanoma compared to prior treatment regimens. Serious adverse events, including the development of cutaneous malignancies, are reported at lower rates with combination therapy, while less severe events such as pyrexia can be more common. Existing data is lacking for a recommendation of triplet therapy, although results from multiple ongoing trials are highly anticipated.


Assuntos
Carbamatos/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzimidazóis/administração & dosagem , Carbamatos/farmacologia , Humanos , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/farmacologia
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