Publications by authors named "Juan Antonio Nuñez"

3 Publications

  • Page 1 of 1

Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non-Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments.

Clin Lung Cancer 2018 01 23;19(1):65-73.e7. Epub 2017 Jun 23.

Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.

Introduction: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.

Patients And Methods: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs.

Results: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials.

Conclusion: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.
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January 2018

Second-line Treatment of Non-Small Cell Lung Cancer: Focus on the Clinical Development of Dacomitinib.

Front Med (Lausanne) 2017 5;4:36. Epub 2017 Apr 5.

Medical Oncology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación i+12, Madrid, Spain.

Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine-kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in experimental models, including first-generation TKI-resistant non-small cell lung cancer (NSCLC) cell lines. This preclinical efficacy did not translate into clinically meaningful treatment benefits for advanced, pretreated, molecularly unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib and erlotinib showed overlapping efficacy data in chemotherapy-pretreated wild-type (WT) patients in the ARCHER 1009 trial. Similarly, it failed to demonstrate any survival benefits as compared to placebo in WT subsets progressing on chemotherapy and at least one previous first-generation TKI (erlotinib or gefitinib) in the BR.26 trial. In the case of -mutant NSCLCs, a pooled analysis of the ARCHER 1009 and ARCHER 1028 trials comparing the efficacy of dacomitinib vs. erlotinib in chemotherapy-pretreated, EGFR TKI-naïve patients showed a trend to a longer progression-free survival (PFS) and overall survival in favor of dacomitinib that did not reach statistical significance, with a higher rate of treatment related adverse events (mainly skin rash, paronychia, and gastrointestinal toxicities). On the other hand, the clinical activity in patients with -mutant NSCLCs with acquired TKI resistance that were included in phase II/III trials was equally poor (response rate <10%; PFS 3-4 months). Therefore, with the results of the ARCHER 1050 trial (NCT01774721) still pending, the current clinical development of dacomitinib is largely focused on -mutant, TKI-naïve patients. Here, we review the most relevant clinical data of dacomitinib in advanced NSCLC. We discuss the potential role of dacomitinib in pretreated WT and -mutant (TKI-naïve and TKI-resistant) patients. Finally, we briefly comment the available clinical data of dacomitinib in HER2-mutant NSCLC patients.
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April 2017

The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects.

J Thorac Dis 2014 Oct;6(Suppl 5):S526-36

1 Medical Oncology Department, 2 Pathology Department, Hospital 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre i+12, Madrid, Spain.

The new the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) pathologic classification of lung cancer has markedly changed the pathologic diagnosis of lung adenocarcinoma. This classification deals with many aspects that directly affect clinical practice, and opens new gateways for future research. By means of a multidisciplinary approach, it differs significantly from the former 2004 the World Health Organization (WHO) classification, which was mainly written by pathologist. The present review, in line with the consensus article, is divided in two components: the diagnosis and classification of lung adenocarcinoma in resection specimens and the diagnosis of lung cancer in small biopsies and cytology. Resection specimens are currently classified according to the predominant histologic pattern after comprehensive subtyping in 5% increments. This approach has led to the addition of new pathologic subtypes [adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and micropapillary predominant adenocarcinoma)] and to the discontinuation of some heterogeneous entities included in the former 2004 WHO classification (mixed subtype adenocarcinoma and bronchioloalveolar carcinoma). Overall, these changes have resulted in a better stratification of lung adenocarcinoma tumors in more homogeneous morphologic, clinical and biological subgroups. Pathologic subtyping has demonstrated prognostic utility in resected stage I-III patients, and recent data support their predictive role for the benefit of adjuvant chemotherapy. Moreover, comprehensive pathologic subtyping may potentially affect TNM staging and surgical management or early-stage tumors. On the other hand, for the first time, the novel pathologic classification provides standardized terminology and diagnostic criteria of small biopsies and cytology. Criteria are proposed not only for adenocarcinoma but also for other histologies, but special emphasis was put on the distinction between adenocarcinoma and squamous-cell carcinoma due to its major clinical implications. This review outlines the main issues of the new lung adenocarcinoma classification from a clinical perspective. We describe the different pathologic subtypes in resection specimens, with their most relevant clinical implications. Further on, we address the new terminology and diagnostic criteria for lung adenocarcinomas in small specimens, oriented to their importance for the management and treatment of metastatic lung cancer patients. Finally, we discuss some unanswered questions and relevant issues for the near future.
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October 2014