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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]

Cutaneous melanoma is one of the most lethal tumors among skin cancers, characterized by complex genetic and molecular alterations that result in uncontrolled cell proliferation and metastatic spread. Next-generation sequencing (NGS) enables the simultaneous examination of numerous genes, making this molecular technique essential for melanoma diagnosis, prognostic stratification, and therapy planning. Herein, we present the experience with our laboratory-designed NGS panel for the routine assessment of advanced-stage melanoma. A total of 260 specimens of advanced-stage melanomas were evaluated utilizing a laboratory-developed multi-gene NGS panel, which allowed the investigation of 229 amplicons in 25 oncogene/oncosuppressor genes. The NGS panel proved to be a reliable tool, failing to produce results in only 1.2% of the samples tested. BRAF and TERT were the two more commonly altered genes in 44.0% and 59.9% of samples, respectively. In 59.3% of the mutated cases, at least two concomitant variants were detected. In eight cases, both primary lesion and metastatic disease were analyzed by NGS. In all specimens (8/8, 100%), a perfect concordance in variants harbored by the primary and recurrence lesions was observed. Finally, this study described the validity of a laboratory-developed multi-gene NGS panel built specifically for advanced-stage melanomas in ordinary clinical practice. [ABSTRACT FROM AUTHOR]

This article discusses the effective management of infiltrative locally advanced basal cell carcinoma (laBCC) of the tibia using sonidegib, a hedgehog inhibitor. The case study presented involves an 81-year-old man with a histologically confirmed laBCC of the right leg that had invaded subcutaneous tissues and the bone. Surgical excision and radiotherapy were not possible, so systemic treatment with sonidegib was proposed and started. After 14 months of treatment, the patient showed a complete response with no evidence of relapse or treatment-related adverse events. This case highlights the potential of hedgehog inhibitors as a viable option for treating laBCC involving the bone, avoiding demolitive surgery and its impact on patients' quality of life. [Extracted from the article]

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]

Simple Summary: The acceptable safety profile of immunotherapy may affect the risk-benefit ratio analysis of treatment prescription near the late stage of life for advanced non-small cell lung cancer patients. The aim of our retrospective study was to describe the clinical characteristics of patients receiving immunotherapy in the last stages of life and to evaluate the accuracy in predicting short-time mortality of LIPI and PaPwCPS scores. Our findings demonstrated an increased tendency in immunotherapy use in during the last month of life. In this context, a laboratory and clinical score such as the PaPwCPS may improve the physician's ability to predict early mortality for immunotherapy-eligible patients. Background: An acceptable risk-benefit ratio may encourage the prescription of immune checkpoint inhibitors (ICI) near the late stage of life. The lung immune prognostic index (LIPI) was validated in advanced non-small cell lung cancer (NSCLC) patients treated with ICIs. The palliative prognostic (PaP) score without clinical prediction of survival (PaPwCPS) predicts early mortality probability in terminal cancer patients. Methods: We performed a retrospective study including 182 deceased advanced NSCLC patients, treated with single-agent ICI at our Institution. Two prognostic categories of high and low mortality risk were identified through ROC curve analysis for PaPwCPS and LIPI scores. Results: Most were >65 years of age (68.3%) and received second-line ICI (61.2%). A total of 29 (15.9%) and 131 (72.0%) patients died within 30 and 90 days from treatment start, respectively. A total of 81 patients (44.5%) received ICI during the last month of life. Baseline PaPwCPS and LIPI scores were assessable for 78 patients. The AUC of ROC curves was significantly increased for PaPwCPS as compared with LIPI score for both 30-day and 90-day mortality. A high PaPwCPS score was associated in multivariate analysis with increased 30-day (HR 2.69, p = 0.037) and 90-day (HR 4.01, p < 0.001) mortality risk. A high LIPI score was associated with increased 90-day mortality risk (p < 0.001). Conclusion: We found a tendency towards ICI prescription near the late stage of life. The PaPwCPS score was a reliable predictor of 30- and 90-day mortality. [ABSTRACT FROM AUTHOR]

The impact of baseline versus intercurrent steroids on the efficacy of upfront chemotherapy plus pembrolizumab (CT-ICI) for advanced non-small cell lung cancer (NSCLC) patients is unclear. We conducted a retrospective study on metastatic NSCLC patients treated with upfront CT-ICI at our institution between March 2020 and December 2021. The use of steroids was considered as the administration of at least 10 mg of prednisone equivalent. Of 101 patients, 36 (35.6%) received steroid therapy at baseline, and 18 (17.8%) started steroids on treatment. Overall, median progression-free survival (mPFS) was 6.5 months (95% CI, 5.9–8.9) and median overall survival (mOS) was 18.2 months (95% CI, 8.9-NR). Patients taking baseline steroids had significantly shorter survival than those not taking them and those assuming intercurrent steroids (mPFS 5.0 vs. 9.2 vs. 7.3 months, p < 0.001; mOS 7.0 months vs. not reached, p < 0.001). Baseline steroids were significantly associated with poorer survival outcomes in the multivariate model (OS HR 2.94, p = 0.02; PFS HR 3.84, p > 0.001). Conversely, intercurrent prescription did not reach a significant value regardless of other pivotal variables included in the model. Baseline steroid administration was associated with a detrimental effect on survival outcomes in NSCLC patients treated with CT-ICI. The role of intercurrent steroid administration should be further explored in larger studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) patients harboring BRAF non-V600 alterations constitute a heterogeneous and poorly studied population orphan of targeted therapies. We conducted a systematic review to detect all BRAF alterations of defined functional class across different cancer types. Then, we searched for NSCLC patients harboring these alterations in the cancer bioportal and in POPLAR and OAK trials using patient-level data, to investigate clinical and genomic differences associated with each BRAF functional class and the prognostic impact of BRAF non-V600 mutations. We found that NSCLC patients harboring distinct classes of BRAF alterations have different clinical characteristics, clinical features and genomic landscape. Moreover, BRAF non-V600 alterations were associated with a poor prognostic impact, apparently regardless of the treatment received. These peculiar features may suggest the use of tailored treatments according to each class of BRAF alteration. Background: In non-small cell lung cancer (NSCLC), BRAF class 1 alterations are effectively targeted by BRAF inhibitors. Conversely, targeted therapies have very low or absent activity in patients carrying class 2 and 3 alterations. The spectrum of BRAF alterations in NSCLC patients, and their accompanying clinical features, genomic landscape and treatment outcomes have been poorly reported. Patients and methods: We identified BRAF alterations of defined functional class across different tumors through a systematic review. Then, we selected NSCLC patients carrying BRAF alterations, according to the systematic review, in the cBioPortal (cBioPortal cohort) to collect and analyze clinical, biomolecular and survival data. Finally, we identified NSCLC patients carrying BRAF non-V600 mutations enrolled in POPLAR and OAK trials (POPLAR/OAK cohort), extracting clinical and survival data for survival analyses. Results: 100 different BRAF non-V600 alterations were identified through the systematic review. In the cBioPortal cohort (n = 139), patients harboring class 2 and 3 alterations were more frequently smokers and had higher tumor mutational burden compared to those carrying class 1 alterations. The spectrum of most frequently co-altered genes was significantly different between BRAF alterations classes, including SETD2, STK11, POM121L12, MUC16, KEAP1, TERT, TP53 and other genes. In the POPLAR/OAK cohort, patients carrying non-V600 BRAF alterations were characterized by poor prognosis compared to BRAF wild-type patients. Conclusions: Different classes of BRAF alterations confer distinctive clinical features, biomolecular signature and disease behavior to NSCLC patients. Non-V600 alterations are characterized by poor prognosis, but key gene co-alterations involved in cancer cell survival and immune pathways may suggest their potential sensitivity to tailored treatments. [ABSTRACT FROM AUTHOR]

Metastatic uveal melanoma (MUM) is the most common form of noncutaneous melanoma. It is different from its cutaneous counterpart and is characterized by a very poor prognosis. Despite groundbreaking improvements in the treatment of cutaneous melanoma, there have been few advances in the treatment of MUM, and standard treatments for MUM have not been defined. We performed a systematic review focusing our attention on all interventional studies, ongoing or already published, concerning the treatment of MUM. We present results from studies of chemotherapy, targeted therapy, immunotherapy and liver-directed therapies. Although the results in this setting have been disappointing until now, trials investigating novel immunotherapeutic strategies alone and in combination with targeted agents and liver-directed therapies are ongoing. [ABSTRACT FROM AUTHOR]

Sonidegib is a HHI (Hedgehog Inhibitor) approved for the treatment of advanced basal cell carcinoma (BCC) with an objective response rate of 60.6% (central review) and 74.2% (investigator review) and a median duration of response of 26.1 months in the pivotal trial BOLT.[1] We herein report the case of a patient with basosquamous carcinomas (BSC) treated with Sonidegib in a neoadjuvant setting. We discussed the case in multidisciplinary tumour board and, considering the extension of the zygomatic lesion and the multiple local recurrences of the other tumours, Sonidegib treatment was started at the regimen of 200 mg daily in May 2020 in a neoadjuvant setting. Moreover, the partial response of the SCC component to HHIs of both tumours of the scalp offered, even in those cases, an easier surgical approach. [Extracted from the article]

We report the case of a young woman who developed metastatic melanoma in the inguinal nodal region, which acquired chondrosarcomatous differentiation and preserved the BRAF mutation found in the primary tumor. The patient was treated with a BRAF/MEK inhibitor combination therapy (dabrafenib/trametinib), which was demonstrated to be effective and well‐tolerated. [ABSTRACT FROM AUTHOR]

Melanoma in giant congenital nevus (M‐GCN) is a rare and potentially lethal neoplasm. In children, M‐GCN appears as a dermal/deep‐seated melanoma (DDM‐GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs‐GCN). DDM‐GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM‐GCN in a 34‐year‐old man characterized with a large‐panel next‐generation sequence (NGS) highlighting a TP53 mutation with a UV‐signature (C>T substitution) in DDM but not in PNs‐GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV‐induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM‐GCN. [ABSTRACT FROM AUTHOR]

Despite of the emerging new systemic and local oncologic treatments (immunotherapy and checkpoint inhibitors, oncolytic viral treatments and injected immunostimulants) the management of skin melanoma metastasis can be still challenging. The main aim of this review was to assess the efficacy and the role of imiquimod in local metastatic melanoma disease. An extensive literature review was performed from September 2000 to March 2020 using PubMed, MEDLINE, Embase, and Cochrane Library databases. Selected articles regarded topical imiquimod, its mode of action as an antitumoral agent and its applications in melanoma metastases treatment. We analyzed a total of 18 published article of clinical cases and small case series and five studies: two retrospective large case series, two Phase I and II clinical trials and one cohort non randomized study. Generally, the treatment is safe and well tolerated. Imiquimod lead to an unstable locoregional control. The use of topical imiquimod for the treatment of MM cutaneous metastases should be considered in selected cases and in palliative settings. [ABSTRACT FROM AUTHOR]

Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit. Materials and methods: This is a retrospective cohort study including patients with stage IIIB–IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well. Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 >8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24–2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04–0.33; p < 0.001), and for CYFRA 21-1 (HR 0.19; 95% CI 0.07–0.55; p 0.002) Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit. [ABSTRACT FROM AUTHOR]

Atherosclerosis is considered an irreversible process, with crucial contribution of inflammation and immune cells. Impact of cancer immunotherapy on a partly immune-driven disease, such as atherosclerosis, is poorly understood, but preclinical models suggest its worsening on programmed death/ligand-1 (PD-1/PD-L1) inhibitors. In a previously reported cohort of 11 patients with non-small cell lung cancer (NSCLC) treated with nivolumab and pre-existing complicated atheromatous plaques, 3 patients had a dramatic radiologic reduction of aortic plaques while on nivolumab; of these 3, 2 died receiving no further treatment. The remaining patient was an 83-year-old woman with history of arterial hypertension and hypothyroidism who was diagnosed with locally advanced squamous NSCLC. At relapse, complicated aortic atheromatous plaques were demonstrated on scans. The patient was then treated with nivolumab obtaining stable disease at radiological assessment, which also demonstrated almost complete vanishing of aortic plaques. After relapse and interval treatment with chemotherapy, she experienced new development of aortic atheromatous plaques. At further relapse she received atezolizumab, which yielded disease response and new reduction in aortic plaques, until nearly complete resolution. The observation of a repeated improvement of atheromatous plaques on treatment with PD-1/PD-L1 inhibitors favors the protective role of T cells on atheromatous plaques that is impaired by PD-L1 expression by plaque-associated macrophages. Validation by independent and prospective observation is needed. [ABSTRACT FROM AUTHOR]

Objectives: Malignant acral melanoma (AM) is relatively infrequent in white patients. Molecular investigations have returned variable results regarding the mutational pattern. We sought to describe the mutation profile and clinicopathologic features of AM.Methods: We investigated BRAF, KIT, and NRAS mutational status in a series of 31 AM samples from white patients.Results: Nodular melanoma was the most common histopathologic subtype (48.4%), followed by acral lentiginous melanoma (25.8%) and superficial spreading melanoma (25.8%). BRAF, KIT, and NRAS mutational rates were 12.9%, 17.2%, and 30.0%, respectively. We observed significant associations between KIT mutational status and a thinner Breslow thickness compared with wild-type (WT) status (P = .002), NRAS mutation status and younger age compared with WT. In patients presenting at least one mutation, triple-WT patients presented metastases most frequently.Conclusions: Although these data represent preliminary results, better knowledge of tumor biology and prognosis of AM can support the clinical approach and follow-up. [ABSTRACT FROM AUTHOR]

Head and neck localization may encompass cutaneous and mucosal melanoma. Lentigo maligna melanoma (LMM) is thought to be the most common histopathologic subtype of melanoma in head and neck area, followed by superficial spreading melanomas (SSM), nodular melanomas (NM), and less frequently desmoplastic subtypes of cutaneous melanoma. BRAF mutation was present in 22.6% (12/53) and NRAS in 15% (6/40), and KIT mutation was recorded only in one patient with nodular melanoma; apparently, it was not performed in other sample of LMM, NM, and SSM. [Extracted from the article]

A 54-year-old Caucasian woman had been undergoing regular follow-up at our Melanoma service for a previous nodular melanoma of the dorsum (Breslow thickness 3.6 mm with ulceration). Cutaneous sarcoid-like reaction in a patient treated with target therapy for metastatic melanoma: the hue is the clue Dynamics of chemokine, cytokine, and growth factor serum levels in BRAF-mutant melanoma patients during BRAF inhibitor treatment. [Extracted from the article]

Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives. [ABSTRACT FROM AUTHOR]