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Abstract: Several randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4–6 cycles of first-line chemotherapy, who are fit (performance status 0–1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a “treatment-free period”. Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection. [Copyright &y& Elsevier]

Background: The combination of platinum-based chemotherapy with immune-checkpoint inhibitors (ICIs) is a standard of care option in the front-line treatment of advanced non-small cell lung cancer (NSCLC). Positive efficacy and safety results have been demonstrated with different chemo-ICI combinations in the corresponding clinical trials, however no randomized prospective comparison is available and there is no evidence on how to choose among the available regimens., Methods: A virtual International Expert Panel took place in July 2023 to review data on chemo-ICI regimens available in the first-line setting in patients with NSCLC, and reach common considerations both in clinical practice and in research setting., Results: Overall, all panelists agreed that safety of the chemo-immunotherapy combination regimens is supported by reviewed data, showing no additional toxicity concerns over those of the individual components of each regimen and highlighting differences in toxicity profile based on ICI component (single anti-PD-1 versus double anti-PD-1 and anti-CTLA-4). Among disease characteristics, PD-L1 value (<1%) but not histology was considered a potential selection factor in favor of the combination with dual ICI. With regards to clinical features, the panelists agreed that chemotherapy, whichever the ICI combination regimen, remains the backbone to counteract disease-related symptoms included those conditioning worse performance status. The panelists defined high, medium, and low priorities in clinical research. High priority was attributed to prospectively evaluating the impact of the addition of anti-CTLA-4 on brain metastasis, biomarker subgroups, and the optimal duration and schedule of combination regimens., Conclusions: Based on the available evidence, the panelists reached common considerations on strengths and differences between chemotherapy plus single agent ICI and chemotherapy plus double agent ICIs in patients with advanced NSCLC. In the absence of direct comparison, different toxicity profile and subgroup analysis by PD-L1 are considered as the main potential features to select among the two regimens, however to be confirmed by recommended prospective randomized clinical research., Competing Interests: Declaration of competing interest C. Gridelli received honoraria as speaker bureau or advisory board member or as consultant from MSD, BMS, Roche, Astra Zeneca, Novartis, Pfizer, Menarini, Boehringer, Karyopharm, Eli Lilly, Amgen, Sanofi, GSK, Boehringer Ingelheim. S. Peters received education grants, provided consultation, attended advisory boards and/or provided lectures for the following organizations: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody. T. Mok received education grants, honoraria, provided consultation, attended advisory boards and/or provided lectures for the following organizations: AstraZeneca, Aurora Tele-Oncology Platform, Lunit, ACT Genomics-Sanomics Group, HUTCHMED, Alpha Biopharma, ACEA Pharmaceutical Research, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo/UCB Japan, Fishawack Facilitate, InMed, Lilly, Merck Sharp & Dohme, Novartis, Origimed, Pfizer, Prime Oncology, Roche, Sanofi Aventis GmbH, Taiho Pharmaceutical, Takeda, Lucence, Medscape, Permanyer Publications, PeerVoice, Physicans' Education Resource, Research to Practice, Shanghai BeBirds Translation & Consulting, Liangyihui Network Technology Co, Ltd, AbbVie, Berry Oncology, Blueprint Medicines, C4 Therapeutics, CStone Pharmaceuticals, Curio Science, D3, Eisai, Gilead Sciences, Gritstone Bio, Guardant Health, touchIME, Hengrui Therapeutics, Ignyta, Incyte, Inivata, IQvia, Lilly, Loxo, Lunit, Merck Serono, Mirati Therapeutics, Puma Biotechnology, SFJ Pharmaceuticals Group, Vertex, Yuhan, Qiming Development (HK) Ltd, G1 Therapeutics, Janssen, geneDecode. Stock and Other Ownership Interests: Aurora Tele-Oncology Platform, HUTCHMED, ACT Genomics-Sanomics Group. MC Garassino received education grants, honoraria, provided consultation, attended advisory boards and/or provided lectures for the following organizations: MSD Oncology, AstraZeneca/MedImmune, GlaxoSmithKline, Takeda, Roche, Bristol Myers Squibb, Novartis, Tiziana Life Sciences, Sanofi, Celgene, Daiiki Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Lilly, GlaxoSmithKline, Bayer, Blueprint Medicines, Janssen, Regeneron, Otsuka, AstraZeneca, Roche/Genentech, Spectrum Pharmaceuticals, Ipsen, Exelixis, Amgen. Luis Paz-Ares reports institutional research support from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharpe & Dohme, and Laboratorios Pfizer Ltda.; personal fees (self/family) from Altum Secuency, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly and Company, Genomica, Ipsen Biopharmaceuticals Inc., Janssen Biotech, Merck Sharpe & Dohme, Mirati, Novartis, Laboratorios Pfizer Ltda., PharmaMar, Roche, Servier Pharmaceuticals, and Takeda Oncology; and serves as a board member at Genómica and Altum all outside the submitted work. F. de Marinis received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Novartis, Takeda, Xcovery, and Roche. Dr. Attili reports no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the past few years, new second-line therapies, beyond chemotherapy agents, have become available in clinical practice. To date, several options for the second-line treatment of non-oncogene-addicted NSCLC patients ranging from chemotherapy in combination with antivascular endothelial growth factor receptor to immunotherapeutics are available. In oncogene-driven tumors, the better knowledge of mechanisms of acquired resistance to earlier tyrosine kinase inhibitors is leading to novel active inhibitors now available/in development. The second-line algorithm treatment of NSCLC becomes very intricate and the selection of proper patients with one of the new available therapeutic options is of paramount importance to personalize and optimize the treatment. In this review we discuss the second-line treatment opportunities of addicted as well as not-addicted NSCLC., (Copyright © 2017 Elsevier Inc. All rights reserved.)