Maintenance therapy in NSCLC: why? To whom? Which agent?

Maintenance therapy is emerging as a treatment strategy in the management of advanced non small cell lung cancer (NSCLC). Initial trials addressing the question of duration of combination chemotherapy failed to show any overall survival benefit for the prolonged administration over a fixed number of cycles with an increased risk for cumulative toxicity. Nowadays several agents with different ways of administration and a different pattern of toxicity have been formally investigated in the maintenance setting. Maintenance strategies include continuing with an agent already present in the induction regimen or switching to a different one. Taking into consideration that no comparative trials of maintenance with different chemotherapy drugs or targeted agents have been conducted, the choice and the duration of maintenance agents is largely empirical. Furthermore, it is still unknown and it remains an open question if this approach needs to be proposed to every patient in the case of partial/complete response or stable disease after the induction therapy. Here, we critically review available data on maintenance treatment, discussing the possibility to tailor the right treatment to the right patient, in an attempt to optimize costs and benefits of an ever-growing panel of different treatment options

Women and Lung Cancer: Literature Assumptions and News from Recent Publications

For a long period of time, lung cancer (LC) was considered as a malignancy affecting only males, but epidemiological data have shown a dramatic increase of the incidence of this disease among women, and the gender gap has been narrowing steadily since the 1980s, mainly as a consequence of the huge spread of tobacco consumption during the past 70 years. In 2013, the percentage of current cigarette smokers among adults aged 18 and over in the US was 19.9% for men and 15.2% for women (selected estimates based on data from the January-June 2013 National Health Interview Survey), reflecting the earlier and more marked decline in the prevalence of tobacco use in men. Nowadays, cigarette smoking accounts for >90% of LCs in men and 75-85% of LCs in women in the US and Europe, but 20% of women with LCs have never smoked. Many studies describe differences between males and females in the clinical presentation and biology of LC, suggesting that the disease should be considered a specific entity in women, where adenocarcinoma is the most common histological subtype, and prognosis and response to treatment appear to be different. In line with these findings, hormonal receptors have been isolated in LC tissues: the interaction of oestrogen receptors with growth-factor-receptor signalling is an emerging area of investigation and – considering the potential impact of hormonal factors – lung carcinogenesis appears distinctive in women. Despite these considerations, no ‘gender driven’ diagnostic or therapeutic approaches are available nowadays. Improving knowledge of LC in women will allow identification of specific genetic alterations or hormonal profiles which could be targeted by therapy in order to stimulate research progress towards personalised sex-based investigations

Alectinib in the treatment of ALK-positive non-small cell lung cancer: an update on its properties, efficacy, safety and place in therapy

Anaplastic lymphoma kinase (ALK) rearrangement is identified in 3–7% of advanced non-small cell lung cancer (NSCLC) cases, and ALK tyrosine kinase inhibitors (TKIs) have revolutionized the management of this subset of NSCLC patients. ALK–TKIs have been proven highly effective in ALK-rearranged advanced NSCLC patients, but after initial responses and benefit, a subsequent progression inevitably occurs. Understanding acquired-resistance mechanisms and defining an appropriate algorithm is becoming even more essential, particularly considering the availability of extremely efficacious next-generation ALK inhibitors. The aim of this review is the analysis of current data about ALK inhibition as a therapeutic strategy in ALK-rearranged NSCLC management, with a focus on a specific ALK–TKI, alectinib. Alectinib is a highly selective inhibitor of ALK and showed systemic and central nervous system (CNS) efficacy in the treatment of this particular population. The change of first-line approach, and consequently of further lines of therapy, in ALK-rearranged NSCLC patients is still a matter of debate. A summary of evidence from randomized trials evaluating alectinib will be presented in order to discuss the available clinical evidence, safety and place in therapy

Management of Leptomeningeal Metastases in Non-oncogene Addicted Non-small Cell Lung Cancer

Brain metastases in non-small cell lung cancer (NSCLC) patients are more often detected due to imaging modalities improvements but also emerge because of improved treatments of the primary tumor which lead to a longer survival. In this context, development of leptomeningeal metastases (LM) is a devastating complication and its prognosis remains poor despite advances in systemic and local approaches. Histology characterization of NSCLC and molecular expression influence LM management. For those with “oncogene addiction,” new generation epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) were developed to strongly penetrate the blood-brain barrier (BBB) with the aim to prevent central nervous system cancer dissemination, eventually impacting on LM appearance and its subsequent management. Systemic chemotherapy, often combined with intrathecal chemotherapy (when possible), was one of common indications for lung cancer patients affected by LM, without driver mutations and a good performance status but currently, with the advent of innovative systemic approaches treatment solutions in this subgroup of patients are rapidly evolving. Whole brain radiation therapy (WBRT) is the conventional treatment for patients with brain metastases. Furthermore, modern radiation techniques, as stereotactic radiotherapy (SRT), improve outcomes in those cases with a limited number of lesions. However, LM represent a minority of CNS metastases and few literature data are available to drive the radiotherapy approach. Considering all relevant progress made in this setting, after a literature review, the aim of this paper is to discuss about recent developments and therapeutic options in LM management of non-oncogene addicted NSCLC

Claustrofilia

Da quasi un ventennio – non diversamente da quanto, in varia misura, accade nel resto d’Europa – la scuola italiana è sottoposta a una pressione “riformatrice” che tende a subordinare gli assi formativi dei ragazzi a scopi economici e strumentali. È la scuola-azienda che oramai vediamo profilarsi nitidamente sotto i nostri occhi. Oggi i legislatori europei e italiani chiedono che già a partire dai 5-6 anni i bambini sviluppino attitudini alla competizione, a fare impresa, ad “assumersi rischi”, ecc. Con la legge della “Buona Scuola” e l’alternanza scuola-lavoro si pretende addirittura di risolvere il «problema della disoccupazione in Italia» – questione mondiale che ha bisogno di ben altra cura – facendo perdere sino a 400 ore di studio ai nostri ragazzi, spesso sottoposti a sfruttamento da imprese private. Il libro Aprire le porte, opera a più mani di insegnanti, docenti universitari e studiosi di varia formazione, mette soprattutto a nudo gli errori e i danni di questa stagione di destrutturazione della nostra scuola. Ma al tempo stesso propone idee e linee riformatrici nuove in grado di rimettere questa istituzione al centro di un processo educativo non finalizzato al mercato del lavoro, ma alla formazione di persone in grado di affrontare le complesse sfide del nostro tempo

The Genomics of Young Lung Cancer: Comprehensive Tissue Genomic Analysis in Patients Under 40 With Lung Cancer

INTRODUCTION: Lung adenocarcinomas in young patients (<40 y) are more likely to harbor targetable genomic alterations. This study aimed to determine whether the prevalence of targetable alterations is greater in young adults with lung carcinoma than in the overall lung cancer population. To reach this rare patient population, a web-based platform was used to recruit and enroll patients remotely. METHODS: In this prospective study, patients less than 40 years old at the time of primary lung cancer diagnosis with confirmed lung carcinoma were recruited from four global sites and remotely by means of a website. Genotyping data were collected, if available, or obtained by means of next-generation sequencing using the FoundationOne platform. The prevalence of targetable alterations was quantified across patients with advanced adenocarcinoma. RESULTS: Overall, 133 patients across five continents were included, 41% of whom enrolled online. The mean (SD) age at diagnosis was 34 (5.2) years; 79% had stage IV disease at diagnosis. Among patients with adenocarcinoma (n = 115), 112 entered the study with previous genomic testing results and 86 (77%) had targetable alterations in EGFR, ALK, ROS1, MET, ERBB2, or RET. Among those without targetable alterations, 14 received further testing and a targetable alteration was identified in eight (57%). CONCLUSIONS: This study revealed the feasibility of using a web-based platform to recruit young patients with lung cancer and revealed that 94 of 112 (84%) with adenocarcinoma at any stage had targetable genomic alterations. Among patients with stage IV adenocarcinoma, 85% had a targetable alteration, which is higher than historical expectations for the general population