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Since melanoma incidence is steadily increasing, guidelines regarding the diagnosis, staging, and treatment of melanoma are constantly being updated. In particular, the use of adjuvant therapy in stage IIb/c melanoma has been recently approved by the international regulatory agenicies. We performed a retrospective study with 92 melanoma patients namely 42 patients with IIb/c melanoma and 42 patients with IIIa stage melanoma, describing demographics, clinical, histology and disease course during the 5-year follow-up. Several significant evidences emerged between the two groups. Stage IIb/c patients possess a higher age of disease onset (69.6 vs. 55.5 years) with respect to stage III patients and the acral localization appeared as the most frequent (24% vs. 4%). Histologically, stage IIb/c melanomas more frequently exhibit ulceration (70% vs. 2%), angiotropism (54% vs. 8%) and are characterized by a greater presence of TILS (52% vs. 15%). Although it is not statistically significant, we observed a difference in terms of presence of metastasis during the 5-year follow-up: 15% of stage IIb/c patients showed metastasis vs. 4% of stage IIIa patients. Our data support the use of adiuvant immunotherapy in stage IIb/c patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Following surgery, dabrafenib and trametinib have been approved for the treatment of stage III melanoma with a B-RAF gene mutation. A retrospective–prospective observational trial conducted in Italy, known as MADAM (Maximizing ADjuvAnt MAP), included patients who had received at least one dose of trametinib plus dabrafenib. Following the first 24 months of follow-up, this analysis was the first. The trial involved 310 patients in total, of whom 240 completed the 12-month course of treatment, while 70 discontinued therapy. At 24 months, the majority of patients (80.2%) were alive and had not experienced disease relapse. The combination of trametinib and dabrafenib appears to benefit patients by lowering the rate of relapse. Background/Objective: Dabrafenib and trametinib (D + T) have been approved for the treatment of stage III melanoma with BRAF V600E V600K mutations in an adjuvant setting, based on the results from the COMBI-AD trial. To provide early access to this combination therapy prior to its commercial availability in Italy, a Managed Access Program (MAP) was run in Italy from June 2018 to December 2019. Methods: The MADAM (Maximing ADjuvAnt MAP) study is an Italian retrospective–prospective observational study that included patients who received at least one dose of D + T through the MAP. The primary endpoints were relapse-free survival (RFS) and overall survival (OS). Results: This interim analysis presents findings after the first 24 months of follow-up. A total of 310 patients were included in the study; 240 completed the 12-month treatment with D + T, while 70 discontinued the combination. RFS rates were 93.2% at 12 months and 80.2% at 24 months. The median RFS was not reached for the overall population or any subgroups. Similarly, the median OS was not reached, with OS rates of 96.4% at 12 months and 92.5% at 24 months. Conclusions: D + T achieved an RFS benefit, with effects sustained beyond the treatment period, indicating positive outcomes in this patient population. [ABSTRACT FROM AUTHOR]

We report the case of an 87-year-old female patient who was diagnosed with metastatic non-small-cell lung cancer harboring MET exon 14 skipping mutation (MET ex14) and PD-L1 expression of 60%. A first-line treatment with atezolizumab was started with primary resistance. Then, a second-line treatment with capmatinib, a selective type Ib MET tyrosine kinase inhibitor, was started, achieving a partial response. The patient is still alive and on treatment with capmatinib 300 mg twice daily after 20 months, with a good tolerability and no evidence of disease progression. In summary, our patient experienced a long-lasting response (>18 months) with capmatinib as second-line treatment. Further analyses evaluating the efficacy and tolerability of MET tyrosine kinase inhibitors are warranted, especially in the elderly, a non-small-cell lung cancer population whose tumors could more frequently harbor MET ex14 mutation. Executive summary Lung cancer is the leading cause of cancer related death. Tyrosine kinase inhibitors targeting specific genetic alterations in non-small-cell lung cancer (NSCLC) significantly improved response rate and survival outcomes. MET exon 14 skipping mutations, found in 3–4% of NSCLC, are more frequent in elderly patients. Capmatinib and tepotinib demonstrated efficacy for MET ex14 skipping mutations. Our case report showed capmatinib effectiveness in elderly NSCLC patient, maintaining a good quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Real-world data from patients with BRAFV600-mutated, resected, stage III melanoma treated with dabrafenib plus trametinib as adjuvant targeted therapy are limited, and it is important to gain an understanding of the characteristics of this patient population, as well as of the patient journey. Here we aimed to describe the characteristics, dosage reductions and discontinuations in patients with BRAFV600E/K-mutated melanoma receiving adjuvant dabrafenib plus trametinib after surgical resection through an Italian managed access program (MAP).Patients and Methods: Eligible patients had completely resected cutaneous melanoma with confirmed BRAF V600E or V600K mutation, or initially resectable lymph node recurrence after a diagnosis of stage I or II melanoma. The starting dose of dabrafenib and trametinib was 150 mg twice daily and 2 mg once daily, respectively.Results: A total of 557 patients received dabrafenib plus trametinib through the MAP (stage III resected disease at inclusion, 554). Median age was 54.0 years, and 40.2% of patients were female. The proportion of all treated patients who required a dose reduction was low (10.8%) as was the proportion of patients who discontinued treatment (13.5%). The main reason for treatment discontinuation was adverse events (36.0%).Conclusion: New treatments, including BRAF-targeted therapies and immunotherapy, have transformed the natural history of melanoma. This is the largest study to date describing patients treated with dabrafenib plus trametinib in routine clinical practice in Italy between 2018 and 2019. Results highlight the characteristics of the patients treated and their journey, as well as the tolerable safety profile of dabrafenib plus trametinib in a real-world patient population. [ABSTRACT FROM AUTHOR]

This article examines the different types of basal cell carcinomas (BCCs) and their response to vismodegib treatment in patients with Gorlin-Goltz syndrome (GGS), an inherited disorder that increases the risk of developing multiple BCCs. The study involved six patients who received vismodegib treatment, and the response was assessed using RECIST v1.1 guidelines. The findings suggest that certain histological subtypes of BCCs, particularly pigmented BCCs, are more likely to respond to treatment. However, more research is needed to confirm these results. The article includes tables displaying response rates of different lesions to treatment and the frequency of clinically and dermoscopically evident BCCs at different time points. No funding information or conflict of interest statement is provided. [Extracted from the article]

Background: many patients with non-small cell lung cancer (NSCLC) derive poor benefit from immunotherapy (IO). For some of them, adding chemotherapy (CT) can improve the outcomes, but the reliability of PD-L1 expression as the only biomarker to distinguish these patients is unsatisfactory. We sought to detect clinicopathological and molecular predictive factors of survival that might be added to PD-L1 expression in the selection of patients that should receive IO alone or chemoimmunotherapy (CIT).Methods: We conducted a systematic search of randomized controlled clinical trials (RCT) investigating IO, alone or plus CT, versus CT alone in treatment-naïve advanced NSCLC patients. Meta-analyses and meta-regression analyses were performed to investigate IO alone versus CT, CIT versus CT, and IO alone versus CIT.Results: 14367 patients with advanced NSCLC across 25 RCT were included. Squamous histology, male sex, current/former smoker status, PD-L1 expression ≥50%, and high tumor mutational burden (TMB) correlated with improved survival with IO alone compared to CT. Conversely, female sex, no smoking history, negative PD-L1 expression, and low TMB correlated with unsatisfactory outcomes with IO alone versus CT, but not with CIT versus CT. CIT improved survival versus IO alone in female patients, never smokers, in those having a PD-L1 expression ≥1% (but not with PD-L1 ≥50%) or a low TMB, and in patients with central nervous system metastasis.Conclusion: these findings suggest some clinicopathological and molecular features that, added to PD-L1 expression, could help in the selection of the most appropriate first-line IO-based treatment for advanced NSCLC patients. [ABSTRACT FROM AUTHOR]