Stefano Frega

Immunotherapy-related skin toxicity: bullous pemphigoid in a lung adenocarcinoma patient treated with the anti-PDL1 antibody atezolizumab

Immune checkpoint inhibitors are monoclonal antibodies (mAb) belonging to different categories, namely those that block cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death 1 (PD1) expressed on T-cells, or programmed-death ligand 1 (PD-L1) expressed on tumour and antigen-presenting cells [1]. Although they have different functions, the common final effect of this class of drugs is the enhancement of the immune response against cancer cells [1]. One of the major PD-L1 inhibitors [...]

A Triple Rare E709K and L833V/H835L EGFR Mutation Responsive to an Irreversible Pan-HER Inhibitor: A Case Report of Lung Adenocarcinoma Treated with Afatinib.

To the Editor: First-generation (gefitinib and erlotinib) and secondgeneration (afatinib) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provided improvements in progression-free survival (PFS) and response rate compared with platinum-based chemotherapy as first-line treatment of patients with advanced mutated non–small cell lung cancer (NSCLC) but without an overall survival (OS) advantage, which is probably due to high treatment crossover across the trials. A recent meta-analysis confirmed higher benefit from TKIs in cases with classical exon 19 deletion. The outcomes of TKI treatment are rather consolidated in the two most common sensitizing mutations (exon 19 E746-A750 deletion and exon 21 L858R), whereas T790M on exon 20 has been recognized as an acquired resistance mutation. Conflicting data about uncommon mutations have been published, and the predictive and prognostic value of rare or complex mutations has not been established yet. Reversible TKIs (gefitinib and erlotinib) achieve limited benefit with uncommon partial sensitizing point mutations G719X, S768I , and L861Q on exons 18, 20, and 21, respectively. Rare exon 19 mutations confer heterogeneous sensitivity, whereas most NSCLCs with an exon 20 insertion mutation have a poor prognosis. The irreversible pan-human EGFR inhibitor afatinib showed limitedefficacy in tumorswithT790Mandexon20 insertions, constituting a valid option in patients with the aforementioned uncommonmutations. The best first-line treatment in exon 20–mutated NSCLC is still under debate.

Non-Small Cell Lung Cancer in a Very Young Woman: A Case Report and Critical Review of the Literature.

Patient: Female, 19 Final Diagnosis: Lung adenocarcinoma Symptoms: Chest pain Medication: — Clinical Procedure: Ct scan and pet-ct Specialty: Oncology Objective: Unusual clinical course Background: Lung cancer in young patients is quite uncommon; clinical presentation and outcome in this population compared to the older group are not yet well defined and data about this setting are mostly single-institutional retrospective analyses. Case Report: We report here a case of a very young woman with diagnosis of early-stage lung adenocarcinoma harboring EML4-ALK rearrangement; she underwent radical surgery and adjuvant chemotherapy according to the pathologic stage. Potential risk factors for lung cancer in our patient are discussed and clinico-pathologic features and outcomes of lung cancer in the young population compared to the elderly are reviewed through discussing studies with sample sizes larger than 100 patients. Conclusions: A wide clinical overview should be performed when lung cancer is diagnosed in a young patient. Large-population studies are required to define the molecular signature and clinical behavior of lung cancer in young patients.

Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization.

Therapeutic perspectives for brain metastases in non-oncogene addicted non-small cell lung cancer (NSCLC): Towards a less dismal future?

Risk of brain metastases (BM) affects a remarkable number of non-small cell lung cancer (NSCLC) patients, impacting on their quality of life (QoL) and prognosis. While tyrosine-kinase inhibitors (TKIs) showed interesting intracranial control rates in oncogene-addicted NSCLC, BM still represent an unmet need for the counterpart without driver gene mutations. For these patients, new treatment options include anti-angiogenic drugs and immune-checkpoint inhibitors, possibly combined with standard chemotherapy, even though the benefit on BM has not been clearly defined. A multidisciplinary team including neurosurgeons, medical and radiation oncologists is needed in order to integrate systemic and loco-regional strategies at the right time point. Ad-hoc designed clinical trials are slowly emerging for previously treated patients with uncontrolled BM. The aim of this review is to offer a detailed and updated picture of possible approaches for non oncogene-addicted NSCLC patients having BM, in order to support clinicians in their daily practice.

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified.

166P: Non-small cell lung cancer (NSCLC) patients with rare or complex epidermal growth factor receptor (EGFR) mutations: A single institution series

G. Pasello1, V. Polo2, S. Frega2, M. Lorenzi3, S. Indraccolo4, M. Fassan5, L. Bonanno1, N. Nannini6, P.F. Conte2, F. Calabrese6. 1Medical and experimental oncology department, Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy , 2 Surgical Oncological and Gastroenterological Sciences Department, University of Padova, Padua, Italy, 3Medicine and Surgery Faculty, University of Padova, Padua, Italy, 4 Immunology and Molecular Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5 Surgical Pathology Unit, Department of Medicine, University of Padova, Padua, Italy, 6 Department of Cardiothoracic and Vascular Sciences, University of Padova, Padua, Italy