Systemic Therapies For Melanoma Research Articles

Adjuvant systemic therapy for melanoma - Analysis of factors leading to the timely initiation of treatment

Adjuvant systemic therapy for melanoma - Analysis of factors leading to the timely initiation of treatment

Systemic Therapy for Melanoma: ASCO Guideline Update Q and A.

This Q&A answers questions regarding ASCO's recent Systemic Therapy for Melanoma guideline.

Changes in Health Care Costs, Survival, and Time Toxicity in the Era of Immunotherapy and Targeted Systemic Therapy for Melanoma

Melanoma treatment has evolved during the past decade with the adoption of adjuvant and palliative immunotherapy and targeted therapies, with an unclear impact on health care costs and outcomes in routine practice. To examine changes in health care costs, overall survival (OS), and time toxicity associated with primary treatment of melanoma. This cohort study assessed a longitudinal, propensity score (PS)-matched, retrospective cohort of residents of Ontario, Canada, aged 20 years or older with stages II to IV cutaneous melanoma identified from the Ontario Cancer Registry from January 1, 2018, to March 31, 2019. A historical comparison cohort was identified from a population-based sample of invasive melanoma cases diagnosed from the Ontario Cancer Registry from January 1, 2007, to December 31, 2012. Data analysis was performed from October 17, 2022, to March 13, 2023. Era of melanoma diagnosis (2007-2012 vs 2018-2019). The primary outcomes were mean per-capita health care and systemic therapy costs (Canadian dollars) during the first year after melanoma diagnosis, time toxicity (days with physical health care contact) within 1 year of initial treatment, and OS. Standardized differences were used to compare costs and time toxicity. Kaplan-Meier methods and Cox proportional hazards regression were used to compare OS among PS-matched cohorts. A PS-matched cohort of 731 patients (mean [SD] age, 67.9 [14.8] years; 437 [59.8%] male) with melanoma from 2018 to 2019 and 731 patients (mean [SD] age, 67.9 [14.4] years; 440 [60.2%] male) from 2007 to 2012 were evaluated. The 2018 to 2019 patients had greater mean (SD) health care (including systemic therapy) costs compared with the 2007 to 2012 patients ($47 886 [$55 176] vs $33 347 [$31 576]), specifically for stage III ($67 108 [$57 226] vs $46 511 [$30 622]) and stage IV disease ($117 450 [$79 272] vs $47 739 [$37 652]). Mean (SD) systemic therapy costs were greater among 2018 to 2019 patients: stage II ($40 823 [$40 621] vs $10 309 [$12 176]), III ($55 699 [$41 181] vs $9764 [$12 771]), and IV disease ($79 358 [$50 442] vs $9318 [$14 986]). Overall survival was greater for the 2018 to 2019 cohort compared with the 2007 to 2012 cohort (3-year OS: 74.2% [95% CI, 70.8%-77.2%] vs 65.8% [95% CI, 62.2%-69.1%], hazard ratio, 0.72 [95% CI, 0.61-0.85]; P < .001). Time toxicity was similar between eras. Patients with stage IV disease spent more than 1 day per week (>52 days) with physical contact with the health care system by 2018 to 2019 (mean [SD], 58.7 [43.8] vs 44.2 [26.5] days; standardized difference, 0.40; P = .20). This cohort study found greater health care costs in the treatment of stages II to IV melanoma and substantial time toxicity for patients with stage IV disease, with improvements in OS associated with the adoption of immunotherapy and targeted therapies. These health system-wide data highlight the trade-off with adoption of new therapies, for which there is a greater economic burden to the health care system and time burden to patients but an associated improvement in survival.

Systemic Therapy for Melanoma: ASCO Guideline Update.

To provide guidance to clinicians regarding the use of systemic therapy for melanoma. American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. The updated review identified 21 additional randomized trials. Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies.This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update.Additional information is available at www.asco.org/melanoma-guidelines.

PET-CT underestimates the true pathological extent of disease at lymphadenectomy for melanoma patients after systemic therapy

IntroductionModern systemic therapy has revolutionized the treatment of melanoma. Currently, patients with clinically involved lymph nodes require lymphadenectomy with associated morbidities. Positron Emission Tomography – Computed Tomography (PET-CT) has demonstrated accuracy in melanoma detection and response to therapy. We aimed to identify whether a PET-CT directed lymphatic resection after systemic therapy is oncologically sound. Materials and methodsRetrospective review of patients who underwent lymphadenectomy after systemic therapy for melanoma with a preoperative PET-CT. Examined demographic, clinical, and perioperative parameters including extent of disease, systemic therapy and response, and PET-CT findings compared to pathological outcomes. We compared patients with “as or less than expected” outcomes on pathology against those with “more than expected” pathological outcomes. ResultsThirty-nine patients met inclusion criteria. In 28 (71.8%), pathological outcomes were “as or less than expected” by PET-CT, and in 11 (28.2%) pathological outcome were “more than expected”. “More than expected” occurred more frequently with advanced disease at presentation with 75% presenting with regional/metastatic disease versus only 42.9% in the “as or less than expected” group (p = 0.015). Poor response to therapy also trended towards the “more than expected” group with only 27.3% favorable response versus 53.6% favorable response in the “as or less than expected” group, not statistically significant. Extent of disease on imaging failed to predict pathological concordance. ConclusionPET-CT underestimates pathological extent of disease in the lymphatic basin in 30% of patients after systemic therapy. We failed to identify predictors of more extensive disease and warn against limited PET-CT directed lymphatic resections.

Advanced melanoma-A curable disease? Implications of systemic treatment on patients' daily life.

Advanced melanoma-A curable disease? Implications of systemic treatment on patients' daily life.

Has the advent of modern adjuvant systemic therapy for melanoma rendered sentinel node biopsy unnecessary?

The prognostic value of sentinel node biopsy (SNB) is well established and SNB was therefore adopted as a requirement for pathological staging of melanomas>1 mm thick in the American Joint Committee on Cancer (AJCC) 8th edition. Consequently, a negative SNB status became an eligibility criterion for clinical trials of adjuvant systemic therapy in resected stage IIB/C melanoma. However, since the Keynote 716 trial demonstrated an improvement in relapse-free survival (RFS) in patients with Stage IIB/C melanoma, all of whom had SNB staging, some have argued that SNB is no longer required for patients with T3 and T4 primary melanomas. The rationale for omitting SNB is that these patients will be able to access adjuvant immunotherapy regardless of SNB status, avoiding the costs and potential complications of SNB. However, this argument overlooks the prognostic value of knowing a patient’s nodal status and the therapeutic benefit of SNB in regional disease control. Based on extrapolation of data from multiple sources, we demonstrate that the risk of regional node-field relapse with SNB and immunotherapy for T3b and T4 melanomas is around 7–9% but is 20–27% without SNB. Similarly, the node-field recurrence rate with SNB alone is around 14% compared to around 40% with no SNB or immunotherapy. Consequently, in the absence of prospective data, we propose that the optimal management of the regional node-field for high-risk T3b and T4 primary melanomas is likely to be achieved by combining SNB and adjuvant immunotherapy for those patients who are suitable, rather than either treatment alone.

Robot-assisted pelvic node dissection has similar operative and melanoma outcomes to open pelvic node dissection with shorter hospital stays

Background: Robot-assisted pelvic lymph node dissection (rPLND) has been employed for the surgical management of enlarged lymph nodes to reduce treatment related morbidity. With the adoption of adjuvant systemic therapy in melanoma reducing surgical indications, we set out to investigate its benefits and long-term outcomes compared to open pelvic lymph node dissection (oPLND).

Changes in healthcare costs and survival in the era of immunotherapy and targeted systemic therapy for melanoma.

ObjectivesMelanoma treatment has evolved over the past decade with the adoption of adjuvant and palliative immunotherapies and targeted therapies and changes in use of sentinel node biopsy. The impact on real-world healthcare costs and outcomes is uncertain. Here we examine changes in healthcare costs and survival using administrative data.&#x0D; ApproachUsing data from the universal healthcare system in Ontario, Canada, we examine a propensity-matched, retrospective cohort of patients aged 20+ years with Stage I-IV invasive cutaneous melanoma from 2018-2019 compared with those from 2007-2012. The primary outcomes were public payer’s mean healthcare per-person costs, and overall survival (OS). Costs were estimated with an established case-mix and claim-based costing algorithm for Ontario, in which person-level costs are allocated for the various healthcare utilizations over time. Standardized mean differences were used to compare costs, and the log-rank test and Cox regression were used to compare survival among stage-stratified, propensity-score matched cohorts.&#x0D; ResultsWe identified 1,138 patients with melanoma from 2018-2019 and 7,654 from 2007-2012. After stage stratification and propensity-matching (N=1,101 per cohort), sentinel lymph node biopsy (62.3% vs. 43.4%) and systemic therapy use (27.3% vs. 12.5%) were more frequent in 2018-2019 compared to 2007-2012. 2018-2019 patients had greater mean healthcare (including systemic therapy) costs compared to 2007-2012 with Stage II ($27,835 vs. $21,179), III ($90,508 vs. $46,242) and IV disease ($118,398 vs. $46,500). There was a seven-to-twelve-fold increase in mean systemic therapy costs for treated patients with Stage III ($68,207 vs. $9,832) and IV disease ($80,905 vs. $6,883). OS was greater in 2018-2019 versus 2007-2012 (2-year OS: 87.8% [95% Confidence Interval {CI}: 85.8-89.6%] vs. 83.7% [95% CI: 81.3-85.7%]; Hazard Ratio {HR}: 0.72 [95% CI: 0.59-0.89]; p&lt;0.05).&#x0D; ConclusionThese real-world data highlight trade-offs with adoption of new effective systemic therapies for melanoma, with a greater economic burden to the healthcare system but an associated improvement in survival. Such evolving paradigm changes may prompt dynamic evaluations of healthcare resources and policies to ensure cancer care is sustainable.

Distinct mutational landscapes characterize melanomas metastatic to different anatomical sites.

9562 Background: Despite revolutionary advances in systemic therapies for melanoma, many patients with metastatic disease have limited treatment options and some sites of disease remain particularly challenging to control, such as brain and liver metastases. We sought to define anatomical site-specific mutational profiles of melanoma metastases from which potentially novel personalized therapeutic opportunities may be developed. Methods: Targeted exome genomic profiling was performed via the FoundationOneCDx platform and known or likely pathogenic variants retained for analysis. PD-L1 immunohistochemistry was performed with the Dako 22C3 assay with PD-L1+ defined as tumor proportion score ≥1. Tumor mutational burden (TMB)-high was defined as TMB ≥10mut/Mb. UV signature was calculated using established algorithms. Aberrations in 23 genes potentially actionable in melanoma ( BARD1, BRAF, BRCA1/2, CDKN2A, DDX3X, FANCC, HRAS, IDH1, KIT, KRAS, MAP2K1, NF1, NRAS, PALB2, PIK3CA, PPP6C, PTEN, RAC1, RAD51C/D, RB1, TP53) were compared across metastatic sites including skin, lymph node, lung, liver, and brain. Results: A total of 4918 cutaneous-type melanoma tumors was evaluated, including 2854 skin lesions (primary/metastasis) and metastases from lymph nodes (n = 858), liver (n = 194), lung (n = 342), and brain (n = 200). The commonly mutated genes were CDKN2A (2220/4918, 45.1%), BRAF (2148/4918, 43.7%), NRAS(1347/4918, 27.4%), NF1 (1038/4918, 21.1%), TP53 (1234/4918, 25.1%) and PTEN (1038/4918, 13.5%). Compared with skin lesions, metastases to the lung were enriched for variants affecting NF1 (OR 2.57, p = 8.99e-13), TP53 (OR 1.65, p = 3.04e-04) and depleted in NRAS (OR 0.49, p = 9.00e-06) and BRAF (OR 0.70, p = 1.13e-02). Lung metastases were associated with higher prevalence of UV signatures, PD-L1 positivity and high TMB. PTEN variants were enriched in both brain (OR 3.00, p = 2.38e-08) and small intestine (OR3.46, p = 6.63e-3) metastases. Brain metastases were also enriched for CDKN2A variants (OR 1.56, p = 4.50e-02). Lymph node metastases had lower rates of UV signatures, NF1 variants, or high TMB, but were associated with PD-L1 positivity. Positional analysis of variants revealed that several, including NRAS, MAP2K1, KRAS, HRAS, IDH1, RAC1, GNA11 and GNAQ were highly restricted to hotspot loci, without definite variation by metastatic site. Conversely, variants affecting CDKN2A, PTEN, TP53 and NF1 were distributed widely across the gene, with high levels of non-hotspot mutations observed in skin lesions, suggesting that such non-hotspot subclones contribute less to distant metastatic potential and are lost during disease evolution. Conclusions: We observed distinct and organ site-specific mutational patterns in patients with metastatic melanoma. These data raise the possibility of metastatic phenotype-directed therapy to improve the personalization and outcomes of treatment for this disease.

Immune-related adverse events and symptom burden in patients with melanoma receiving adjuvant immune checkpoint inhibitor.

TPS12147 Background: Adjuvant therapy with immune checkpoint inhibitors (ICIs) is approved for melanoma, but immune-related adverse events (irAEs) remain a challenge. Although acute toxicities are well defined, long-term AEs and impact on quality of life (QOL) are undetermined. Available data derived from clinical trials involve highly selected populations and do not reflect real world experience. Additionally, trials measure outcomes only at predetermined endpoints, and symptoms may vary throughout the course of therapy. Moreover, the pathogenesis of irAEs and symptoms remains poorly understood. We hypothesize that AEs and sustained inflammation induced by adjuvant ICIs increase symptom burden and negatively impact function and QOL in a subset of patients (pts), and elevated expression of pro-inflammatory cytokines and T cell signatures during therapy correlate with toxicity and symptom burden. Our preliminary data identified i) interleukin-6/Th-17 pathway as a possible mediator of irAEs, ii) immune reactivity and increases in inflammatory cytokines are associated with symptom burden in cancer survivors, and iii) prioritized 30 genetic markers conferring risk for irAEs in ICI-treated melanoma pts. Methods: This is a prospective longitudinal cohort study to evaluate potential toxicity/symptom burden and immune correlates in melanoma pts receiving adjuvant ICIs (NCT04990726). A total of 240 pts will be enrolled. Eligibility criteria: age ≥18 years (yrs), surgically resected stage II, III, or IV melanoma, initiating adjuvant nivolumab or pembrolizumab, no prior systemic therapy for melanoma, and no prior autoimmune diseases. Patients will be assessed at baseline (before ICI infusion) and every 3 months (mos) up to 2 yrs or until attrition or death. The primary endpoint is the incidence rate of any irAEs at 12 mos. Demographics, personal/family history, comorbidities, tumor history/stage, prior therapies, performance status, concurrent medications, and other factors that play a role in pts perceptions of disease are collected. At each visit, pts undergo a clinical evaluation to assess potential irAEs, new comorbidities, and tumor recurrence. Patient-reported outcomes of fatigue, depression, sleep disturbance, and QOL are collected at each visit to assess changes from baseline up to 2 yrs. In addition to standard methods of data collection at pre-specified times, we leverage mobile technology to capture symptoms and AEs in real time. Longitudinal blood samples will characterize pts immune signatures from baseline up to 2 yrs to evaluate their association with irAEs, symptom burden, and QOL, and to compare the genotype of pts with and without irAEs. To characterize the effect of adjuvant ICI on bone health, eligible pts are evaluated by whole body dual-energy X-ray absorptiometry at baseline and at 12 mos as an exploratory aim. The study is currently active, and 27 pts are enrolled. Clinical trial information: NCT04990726.

Knockdown of circular RNA hsa_circ_0062270 suppresses the progression of melanoma via downregulation of CDC45.

Although systemic therapies for melanoma have been improved, the 5-year survival rate of this aggressive cancer remains poor. It has been shown that hsa_circ_0062270 was upregulated in patients with melanoma. However, the relevant mechanism of hsa_circ_0062270 in the progression of melanoma remains unclear. The CCK-8, EdU staining, flow cytometry, and transwell assays were used to determine the viability, proliferation, apoptosis and invasion in melanoma cells. An in vivo animal study was performed finally. The level of hsa_circ_0062270 was significantly upregulated in melanoma cells. In addition, hsa_circ_0062270 knockdown markedly inhibited the viability, proliferation, invasion and promoted the apoptosis of melanoma cells. Cell division cycle protein 45 (CDC45) is the host gene of hsa_circ_0062270, and downregulation of hsa_circ_0062270 notably decreased the expression of CDC45 in melanoma cells. Rescue assays confirmed that hsa_circ_0062270 regulated the growth of melanoma cells through CDC45. Moreover, RIP analysis showed that hsa_circ_0062270 interacted with RNA-binding protein (RBP) EIF4A3. Furthermore, in vivo study indicated that knockdown of hsa_circ_0062270 inhibited the melanoma tumor growth in vivo. Downregulation of hsa_circ_0062270 can inhibit the progression of melanoma through downregulation of CDC45. Our findings provide biological mechanisms for the use of hsa_circ_0062270 as a biomarker for melanoma and potential therapeutic target.

Isolated limb perfusion for locally advanced melanoma in the immunotherapy era

BackgroundPrior to the advent of effective systemic therapy for melanoma, isolated limb perfusion (ILP) was the most effective local treatment for advanced in-transit melanoma (ITM). However, many patients who are now treated by ILP will have received prior immunotherapy. We sought to compare response rates to ILP in patients who had previously received immunotherapy compared to immunotherapy naive patients. Materials and methodsAll patients who underwent ILP for ITM between January 2015 and July 2020 for melanoma were identified retrospectively from two tertiary institutions. Surgical morbidity and oncologic outcomes were compared between immunotherapy naive and immunotherapy pre-treated patients. Results97 perfusions were performed for melanoma. Of those, 18 patients had undergone prior immunotherapy. There were no differences in clinicopathological characteristics or perioperative outcomes between cohorts. Surgical morbidity and local toxicity were similar between both cohorts. Patients who underwent immunotherapy prior to ILP had significantly decreased complete response (CR) rates compared with immunotherapy-naïve (6% vs 47%, p = 0.0018) and a significantly decreased overall survival (OS) and distant progression free survival (DPFS) (p = 0.0031 and p = 0.0006 respectively). There was no difference in overall response (OR), partial response (PR), stable disease (SD), progressive disease (PD) and local progression free survival (LPFS) between cohorts. ConclusionOncological outcomes and complete response rates are worse in patients who have received immunotherapy prior to ILP compared with immunotherapy naïve patients. Despite this, ILP is still a valuable second line treatment for local control in patients who have multiple, bulky and/or recurrent ITM post immunotherapy.

A comparison of the efficacy of Isolated limb perfusion for the treatment of in-transit melanoma in patients previously treated with immunotherapy and in immunotherapy naive patients.

Background: Prior to the advent of effective systemic therapy for melanoma, isolated limb perfusion (ILP) was the most effective treatment for advanced in-transit melanoma, with most historical series reporting overall response rates over 70% and complete response rates of 30% or greater. Reports of occasional abscopal effects on metastases outside of the perfusion field suggest that ILP may, in some patients, induce immune activation.

Molecular testing for melanocytic tumors: a practical update.

The work-up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice.

ASO Visual Abstract: Survival Outcomes of Salvage Metastasectomy after Failure of Modern-Era Systemic Therapy for Melanoma

ASO Visual Abstract: Survival Outcomes of Salvage Metastasectomy after Failure of Modern-Era Systemic Therapy for Melanoma

Survival Outcomes of Salvage Metastasectomy After Failure of Modern-Era Systemic Therapy for Melanoma.

Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy. Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic therapy was stratified into BRAF-targeted therapy, immune checkpoint inhibitor immunotherapy, or both. The end points of overall survival (OS), progression-free survival (PFS), and locoregional disease control (LRC) were assessed using Kaplan-Meier curves. Uni- and multivariable Cox regression procedures were used to examine factors associated with OS, PFS and LRC. The study enrolled 190 patients. Among all the patients, the 5-year OS from metastatectomy was 52%, the 3-year PFS was 21%, and the 5-year LRC was 61%. After resection to NED, NPRD, and PRD, the 5-year OS values were 69%, 62% and 8%, respectively. Fewer lines of preoperative therapy, use of preoperative immunotherapy, and resection to NED were predictors of improved OS. After resection to NED, NPRD, and PRD, the 3-year PFS values were 23%, 24% and 10%, and the 5-year LRC values were 61%, 72% and 34%, respectively. Salvage metastasectomy was associated with durable survival and disease control, particularly after resection to NED, preoperative immunotherapy, and fewer lines of preoperative systemic therapy.

Strategizing Screening for Melanoma in an Era of Novel Treatments: A Model-Based Approach.

Benefit-harm tradeoffs of melanoma screening depend on disease risk and treatment efficacy. We developed a model to project outcomes of screening for melanoma in populations with different risks under historic and novel systemic treatments. Computer simulation model of a screening program with specified impact on overall and advanced-stage incidence. Inputs included meta-analyses of treatment trials, cancer registry data, and a melanoma risk prediction study RESULTS: Assuming 50% reduction in advanced stage under screening, the model projected 59 and 38 lives saved per 100,000 men under historic and novel treatments, respectively. With 10% increase in stage I, the model projects 2.9 and 4.7 overdiagnosed cases per life saved and number needed to be screened (NNS) equal to 1695 and 2632 under historical and novel treatments. When screening was performed only for the 20% of individuals with highest predicted risk, 34 and 22 lives per 100,000 were saved under historic and novel treatments. Similar results were obtained for women, but lives saved were lower. Melanoma early detection programs must shift a substantial fraction of cases from advanced to localized stage to be sustainable. Advances in systemic therapies for melanoma might noticeably reduce benefits of screening, but restricting screening to individuals at highest risk will likely reduce intervention efforts and harms while preserving >50% of the benefit of nontargeted screening. Our accessible modeling framework will help to guide population melanoma screening programs in an era of novel treatments for advanced disease.

Engineering bacterial outer membrane vesicles as transdermal nanoplatforms for photo-TRAIL-programmed therapy against melanoma.

Melanoma is an aggressive cancer with rapid progression, relapse, and metastasis. Systemic therapies for melanoma exhibit limited anticancer potential and high toxicity. Here, we developed the outer membrane vesicles derived from transgenic Escherichia coli, modified with αvβ3 integrin peptide targeting ligand and indocyanine green (named as I-P-OMVs), to induce the transdermal photo-TRAIL-programmed treatment in skin melanoma.-OMVs, which are outer membrane vesicles derived from transgenic Escherichia coli, modified with αvβ3 integrin targeting ligand and indocyanine green (named as I-P-OMVs), to induce the transdermal photo-TRAIL-programmed treatment in skin melanoma. I-P-OMVs exhibited excellent stratum corneum penetration and specificity to melanoma. Upon near-infrared irritation, I-P-OMVs not only induced photothermal-photodynamic responses against primary melanoma spheroids but also activated TRAIL-induced apoptosis in disseminated tumor cells, resulting in a complete eradication of melanoma. I-P-OMVs are the first nanoplatforms to induce transdermal photo-TRAIL-programmed therapy in melanoma with enhanced antitumor performance and high safety, having great potential in cancer therapy.

Metastatic melanoma treatment with checkpoint inhibitors in the COVID-19 era: experience from an Italian Skin Cancer Unit.

Linked articles: COVID‐19 SPECIAL FORUM. J Eur Acad Dermatol Venereol 2020; 34: e291–e310 .