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Background: As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment., Methods: EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B). In both arms, Nivo was administered at the dose of 240 mg i.v. every 2 weeks until progressive disease, intolerable toxicity, or for a maximum of 2 years. The primary endpoint was OS., Results: From Sep 2017 to Aug 2020 125 patients (62 Arm A vs 63 Arm B) were randomized from 32 Italian centers. Accrual was stopped early, before the planned sample size (388 pts) was reached, because of registration of ICPIs in 1st-line. Most patients were male (79.2 %), current/former smokers (93.6 %), had stage IV (74.4 %), performance status 0-1 (98.4 %). mOS (95 % CI) was 14.9 (10.4-18.6) months in arm A vs 18.8 (14.4-21.1) months in arm B (HR 1.09, 95 %CI 0.74-1.62, p = 0.659)., Conclusions: In advanced Sq-NSCLC, the use of Nivo as switch maintenance after 1st-line CHT, does not improve OS compared to its use as 2nd-line. Although the optimal use of ICPIs remains in 1st-line, its role as maintenance has to be better investigated., Clinicaltrials: gov: registration number: NCT03542461., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Gelsomino has received honoraria or personal fees for the advisory role or consulting from Eli Lilly, Novartis, AstraZeneca, and Bristol-Myers Squibb. Marcello Tiseo has received institutional research grants from Astra-Zeneca, Boehringer Ingelheim and received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. Diego Cortinovis has received speaker’s bureau/scientific advisor activity for BMS, MSD, AstraZeneca, Sanofi Genzyme, Novartis, Amgen, Takeda, Roche, Janssen. Andrea Ardizzoni has received research grants from Celgene, Bristol-Myers Squibb, Ipsen, and Roche; and honoraria for advisory roles from Bristol-Myers Squibb, Merck Sharp & Dohme, ROCHE, AstraZeneca, and Eli Lilly., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay., Methods: In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice., Results: 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS., Conclusions: This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Small cell lung cancer (SCLC) represents one of the most complex challenges in the oncological field, with a very slow advancement in research, contrary to the rapid evolutionary of the disease. For nearly two years, the mainstay of treatment for extensive-stage disease (ES-SCLC) has been the combination of platinum-based chemotherapy and immunotherapy, following the approval of atezolizumab and subsequently durvalumab, based on a modest, but significant improvement in overall survival compared to chemotherapy alone. The poor prognosis after the failure of first-line treatment explains the need to maximize the duration and efficacy of up-front systemic therapies, in particular, the emerging role of radiotherapy, also in ES-SCLC. On 10 November 2022, a meeting concerning the integrated treatment of patients with ES-SCLC was held in Rome and was attended by 12 specialists in oncology and radiotherapy from various centers in Lazio, under the direction of Federico Cappuzzo, Emilio Bria and Sara Ramella. The aim of the meeting was to share their clinical experience and to provide a series of practical indications in order to support physicians in the correct integration between first-line chemo-immunotherapy and radiotherapy treatments in ES-SCLC.

Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no significant therapeutic advances over platinum and etoposide chemotherapy in the last 20 years until the introduction of immunotherapy. In 2020 atezolizumab, an immune checkpoint inhibitor against PD-L1 was approved in Italy in combination with carboplatin and etoposide for the first-line treatment of patients with extensive stage disease (ES-SCLC), becoming the new standard treatment. On May 20, 2021, a virtual meeting, directed by profs. Federico Cappuzzo and Emilio Bria, was held in which 14 clinicians from different oncology centers in Lazio, Umbria and Sardinia discussed the issues of ES-SCLC patients treatment, after the advent of immunotherapy. The aim of the meeting was to share their clinical experience and to provide a series of practical indications that can support clinicians in the management of ES-SCLC patients in first-line with chemo-immunotherapy.

Lung cancer is a disease extremely heterogeneous in the molecular aspect and knowing the mutational profile of patients is essential in order to initiate the most appropriate treatment. In 2018, alectinib was approved in Italy for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), becoming a new therapeutic option for this patient group which constitutes approximately 3-7% of patients with NSCLC. On October 26th a virtual meeting was held in which 10 clinicians from various oncology centers in Lazio took part on the management of therapy of patients with Alk translocation, directed by Dr. Maria Rita Migliorino. The aim of the meeting was to share their clinical experience and to provide a series of practical that can help clinicians during treatment with target therapies in ALK-positive NSCLC.

Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is followed by a response rate of 70-80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. This review is focused on the evidence for therapeutic strategies in bone and brain metastases due to lung cancer.

Lung cancer is the leading cause of cancer deaths worldwide. Targeting the epidermal growth factor receptor (EGFR) has played a central role in advancing non-small-cell lung cancer (NSCLC) research, treatment, and patient outcome over the last few years. Erlotinib is a human epidermal growth factor receptor Type 1/EGFR tyrosine kinase inhibitor. Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after the failure of at least one prior chemotherapy regimen. We present the results of phase I, II, III, and IV trials. Erlotinib monotherapy has shown a significant improvement in median survival, quality of life, and related symptoms in an unselected population of patients in second- and third-line therapy as a single agent. Most commonly reported erlotinib-related adverse effects were rash and diarrhea. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and nonsmokers have a better response when treated with erlotinib. Ongoing trials seek to improve therapy with this agent in monotherapy or in combination regimens and better understanding of predictors of benefit with therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.