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The Italian Association of Medical Oncology (AIOM) has developed clinical practice guidelines for the treatment of patients with advanced non-small cell lung cancer (NSCLC). In the current paper a panel of AIOM experts in the field of thoracic malignancies discussed the available scientific evidences, with the final aim of providing a summary of clinical recommendations, which may guide physicians in their current practice., Competing Interests: Declaration of Competing Interest Silvia Novello Department of Oncology, University of Turin, AOU San Luigi, Orbassano (Italy) E-mail: silvia.novello@unito.it COI: consultant and/or speaker's fee for Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Abbvie, Celgene, Astra Zeneca and Boehringer Ingelheim. Other co-authors have no COI to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Reliable evaluation of treatment benefit in early phase clinical trials is necessary. The time to progression ratio (TTPr), which compares successive TTP in a single patient, is a powerful criteria for determining targeted or immune therapies efficacy., Methods: We evaluated 205 TTPr in a large cohort of 177 advanced cancer patients enrolled in at least two Phase 1/1b trials (out of 2827 phase 1/1b-treated patients) at Gustave Roussy., Results: This first wide description of TTPr showed that, under the hypothesis of overall absence of treatment line effect, the median TTPr was 0.7 and that 25% of patients presented a TTPr above the conventional efficacy threshold of 1.3., Conclusions: A higher median TTPr and a larger proportion of patients above the 1.3 threshold should therefore be achieved to conclude to drug efficacy. New guidelines for TTPr interpretation and calibration are proposed, which warrant independent prospective validation.

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN)., Patients and Methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR)., Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type., Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity., Clinical Trial Registration: ClinicalTrials.gov: NCT01538381.

Background: Targeted therapies have to date not been successful in the treatment of small cell lung cancer (SCLC). This study aimed to assess the therapeutic activity of sunitinib (an oral, multi-targeted tyrosine kinase inhibitor) using positron emission tomography (PET)-computed tomography (CT) imaging as an early indicator of response., Methods: This was a single-arm phase II study of sunitinib in patients with SCLC who are either chemo naive (extensive disease) or have a 'sensitive' relapse. A loading dose of 150 mg sunitinib was given orally followed by 37.5 mg/d. The primary end-point was disease control rate (DCR) at 8 weeks after the start of treatment and secondary end-points included toxicity of treatment and overall response. PET-CT was carried out at 4 weeks into the treatment. The study was closed early because of low accrual with only 9 of required 48 patients (19%) accrued., Results: Nine patients were registered, seven females and two males with a median age of 65 years and a median duration of sunitinib treatment of 7.4 weeks. DCR at 8 weeks was achieved in two patients, both of whom went on to long periods of disease control, one patient achieved a partial response which lasted 10 months and a second patient had stable disease (minor shrinkage) which lasted 20 months. One of these patients proved to have an atypical carcinoid tumour at rebiopsy after 10 months. DCR and PET-CT imaging both predicted these responses. Grade III-IV toxicities were encountered during treatment, most commonly neutropenia (n = 3), thrombocytopenia (n = 3) and hypermagnesaemia (n = 2). One toxic death occurred due to bronchial haemorrhage., Conclusion: This study emphasises the need for alternate study design and end-points for new drug assessment in SCLC. EudraCT number: 2006-002485-19., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The identification of new targets in cancer biology has changed the traditional approach to cancer diagnosis and treatment and therefore also to drug development. The classical 'one size fits all' approach needed to be modified into a tailored approach that took into account the patient-to-patient variation. Innovative trials are warranted, based on the integration of new types of design and integrating the knowledge coming from new disciplines like bioinformatics, biostatistics, epidemiology and health economics. Several initiatives have started at national levels but also in large pan-European academic organizations [like the European Organization for Research and Treatment of Cancer (EORTC)] in the scope of generating a harmonized healthcare landscape across Europe.

Collection of collateral effects related to toxicities suffered by patients being exposed to anticancer treatments is of crucial importance in clinical practice but also in oncological research. The present paper describes a web application called PaTOS for self-report of anticancer therapy toxicities, and its evaluation in a preliminary interface analysis and then in a feasibility study.