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BACKGROUND: Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of chemotherapy. Promising activity of novel ADCs, namely Trastuzumab Deruxtecan and Patritumab Deruxtecan, has been observed in hard-to treat molecular subtypes, such as HER2-positive and heavily pretreated EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). However, therapeutic advances are expected in certain subgroups of lung cancer patients, including non-oncogene-addicted NSCLC after failure of current standard of care (e.g., immunotherapy with or without chemotherapy, chemo-antiangiogenic treatment). Trophoblastic Cell Surface Antigen 2 (TROP-2) is a surface transmembrane glycoprotein member of the epithelial cell adhesion molecule (EpCAM) family. TROP-2 represents a promising therapeutic target in refractory non-oncogene-addicted NSCLC. METHODOLOGY: We performed a systematic literature search of the clinical trials about TROP-2 directed ADCs in NSCLC referenced in the pubmed.gov database, Cochrane Library database and clinicaltrial.gov database. RESULTS: First-in-humans ADCs targeting TROP-2, namely Sacituzumab Govitecan (SN-38) and Datopotamab Deruxtecan (Dxd), yielded promising activity signals in NSCLC with a manageable safety profile. Most common grade ≥ 3 adverse events (AEs) of Sacituzumab Govitecan included neutropenia (28 %), diarrhea (7 %), nausea (7 %), fatigue (6 %), and febrile neutropenia (4 %). Nausea and stomatitis were the most common all grade AEs with Datopotamab Deruxtecan; dyspnea, amylase increase, hyperglycemia and lymphopenia were reported as grade ≥ 3 AEs in less than 12 % of patients. CONCLUSION: As more effective strategies are needed for patients with refractory non-oncogene-addicted NSCLC, the design of novel clinical trials with ADCs targeting TROP-2 is encouraged as both a monotherapy or combination strategy with existing agents (e.g., monoclonal antibodies targeting immune checkpoint inhibitors or chemotherapy).
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Inmunoconjugados , Neoplasias Pulmonares , Humanos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Camptotecina , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inmunoconjugados/efectos adversos , Inmunoconjugados/uso terapéutico , Irinotecán , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
BACKGROUND: Phase I trials historically involved heavily pretreated patients (pts) with no more effective therapeutic options available and with poor expected outcomes. There are scare data regarding profile and outcomes of pts enrolled into modern phase I trials. Here, we sought to provide an overview of pts' profile and outcome into phase I trials at Gustave Roussy (GR). METHODS: This is a monocentric retrospective study, including all pts enrolled into phase I trials at GR from 2017 to 2021. Data regarding pts' demographics, tumour types, investigational treatments and survival outcomes were collected. RESULTS: In total, 9482 pts were referred for early phase trials; 2478 pts were screened, among which 449 (18.1%) failed screening; 1693 pts finally received at least one treatment dose as part of a phase I trial. Median age of pts was 59 years old (range, 18-88) and most common tumour types included gastrointestinal (25.3%), haematological (15%), lung (13.6%), genitourinary (10.5%) and gynaecologic cancers (9.4%). Amongst all pts treated and evaluable for response (1634 pts), objective response rate was 15.9% and disease control rate was 45.4%. Median progression-free survival and overall survival were, respectively, 2.6 months (95% confidence interval [95% CI], 2.3; 2.8) and 12.4 months (95% CI, 11.7; 13.6). CONCLUSION: As compared with historical data, our study shows that outcomes of pts included into modern phase I trials have improved and that these trials constitute nowadays a valid and safe therapeutic option. These updated data provide facts for adapting the methodology, role and place of phase I trials over the next years.
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Neoplasias , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Supervivencia sin Progresión , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Unravelling the biological processes driving tumour resistance is necessary to support the development of innovative treatment strategies. We report the design and feasibility of the MATCH-R prospective trial led by Gustave Roussy with the primary objective of characterizing the molecular mechanisms of resistance to cancer treatments. The primary clinical endpoints consist of analyzing the type and frequency of molecular alterations in resistant tumours and compare these to samples prior to treatment. Patients experiencing disease progression after an initial partial response or stable disease for at least 24 weeks underwent a tumour biopsy guided by CT or ultrasound. Molecular profiling of tumours was performed using whole exome sequencing, RNA sequencing and panel sequencing. At data cut-off for feasibility analysis, out of 333 inclusions, tumour biopsies were obtained in 303 cases (91%). From these biopsies, 278 (83%) had sufficient quality for analysis by high-throughput next generation sequencing (NGS). All 278 samples underwent targeted NGS, 215 (70.9%) RNA sequencing and 222 (73.2%) whole exome sequencing. In total, 163 tumours were implanted in NOD scid gamma (NSG) or nude mice and 54 patient-derived xenograft (PDX) models were established, with a success rate of 33%. Adverse events secondary to invasive tumour sampling occurred in 24 patients (7.6%). Study recruitment is still ongoing. Systematic molecular profiling of tumours and the development of patient-derived models of acquired resistance to targeted agents and immunotherapy is feasible and can drive the selection of the next therapeutic strategy.
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BACKGROUND: Hepatic arterial infusion (HAI) combined with systemic chemotherapy has shown promising results in patients with unresectable colorectal liver metastases (CRLM), even after failure to systemic therapy. Addition of systemic targeted therapies has been investigated with controversial results regarding tolerance, especially with HAI-floruxidine when combined with systemic bevacizumab. Our study aimed to analyse feasibility, safety and efficacy of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies. METHODS: Between 2005 and 2016, single-centre consecutive patients with unresectable CRLM who received at least one cycle of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies (cetuximab/panitumumab or bevacizumab) were analysed. RESULTS: A total of 89 patients (median age 55 years (range, 26-76 years) who previously received a median number of one systemic chemotherapy regimen (range, 0-5) including oxaliplatin in 78% of cases were included. Median number of HAI-oxaliplatin cycles was 9 (range, 1-28) combined with systemic chemotherapy and targeted therapies (LV5FU2 [63%], FOLFIRI [36%]) plus anti-EGFR (30%), or bevacizumab (70%). Grade 3/4 toxicities included neutropenia (40%), HAI-related abdominal pain (43%) and neurotoxicity (12%). The intent-to-treat objective response rate was 42%, and 45% had stable disease, allowing complete CRLM resection/ablation in 27% of patients. After a median follow-up of 72 months, median overall and progression-free survival was 20 and 9 months, respectively. CONCLUSION: Addition of targeted therapy to systemic chemotherapy combined with HAI-oxaliplatin is feasible, safe and shows promising activity, even after systemic chemotherapy failure.
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Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Oxaliplatino/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Receptores ErbB/antagonistas & inhibidores , Femenino , Fluorouracilo/administración & dosificación , Arteria Hepática , Humanos , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Oxaliplatino/efectos adversosRESUMEN
PURPOSE: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with proven efficacy in patients with ALK-rearranged lung cancer previously treated with first- and second-generation ALK inhibitors. Beside compound mutations in the ALK kinase domain, other resistance mechanisms driving lorlatinib resistance remain unknown. We aimed to characterize the mechanisms of resistance to lorlatinib occurring in patients with ALK-rearranged lung cancer and design new therapeutic strategies in this setting. EXPERIMENTAL DESIGN: Resistance mechanisms were investigated in 5 patients resistant to lorlatinib. Longitudinal tumor biopsies were studied using high-throughput next-generation sequencing. Patient-derived models were developed to characterize the acquired resistance mechanisms, and Ba/F3 cell mutants were generated to study the effect of novel ALK compound mutations. Drug combinatory strategies were evaluated in vitro and in vivo to overcome lorlatinib resistance. RESULTS: Diverse biological mechanisms leading to lorlatinib resistance were identified. Epithelial-mesenchymal transition (EMT) mediated resistance in two patient-derived cell lines and was susceptible to dual SRC and ALK inhibition. We characterized three ALK kinase domain compound mutations occurring in patients, L1196M/D1203N, F1174L/G1202R, and C1156Y/G1269A, with differential susceptibility to ALK inhibition by lorlatinib. We identified a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors. CONCLUSIONS: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.
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Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/genética , Lactamas Macrocíclicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Aminopiridinas , Animales , Línea Celular Tumoral , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Femenino , Reordenamiento Génico , Humanos , Lactamas , Lactamas Macrocíclicas/uso terapéutico , Estudios Longitudinales , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Mutación , Neurofibromina 2/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This phase 1b, open-label trial assessed the combination of afatinib, an ErbB family blocker, with cetuximab, an epidermal growth factor receptor (EGFR) monoclonal antibody, in heavily pretreated patients with unselected/EGFR wild-type, advanced solid tumours. In Part A, the maximum tolerated dose (MTD) of afatinib + cetuximab was evaluated using a 3 + 3 dose-escalation design; the starting dose was afatinib 30 mg/day plus cetuximab 250 mg/m2/week (after cetuximab 400 mg/m2 loading dose), escalating to afatinib 40 mg/day. Part B further evaluated safety and tolerability at the MTD and preliminary anti-tumour activity in three patient cohorts with squamous non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and other solid tumours. Nine patients were treated in Part A; the MTD and recommended dose was determined as afatinib 40 mg/day plus cetuximab 250 mg/m2/week. In Part B, 49 patients were treated at the recommended dose (12 with squamous NSCLC, 15 with HNSCC and 22 with other tumours). The most common treatment-related adverse events (AEs) across all 58 patients were diarrhoea (63.8%) and acneiform dermatitis (43.1%). Overall, the best confirmed response was stable disease (SD; 53.4%); mean duration of disease control was 4.5 months; median progression-free survival was 2.6 months. In Part B, 55.1% of patients had SD (squamous NSCLC, 75.0%; HNSCC, 66.7%; other tumours; 36.4%). In conclusion, the recommended phase 2 dose was determined as afatinib 40 mg/day plus cetuximab 250 mg/m2/week. AEs were predictable and manageable, and anti-tumour activity was observed in some patients, particularly in those with squamous NSCLC and HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02020577.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Erupciones Acneiformes/inducido químicamente , Afatinib/administración & dosificación , Afatinib/efectos adversos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Cetuximab/administración & dosificación , Cetuximab/efectos adversos , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Erupciones por Medicamentos/etiología , Receptores ErbB/análisis , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Neoplasias/química , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
INTRODUCTION: Diffuse gastric cancer is associated with poor prognosis. We report a patient with metastatic gastric linitis plastica harboring human epidermal growth factor receptor 2 (HER2) activating mutation and HER2 amplification. CASE DESCRIPTION: The patient received 5-fluorouracil/folinic acid and oxaliplatin combined with trastuzumab/pertuzumab, resulting in disease control for 8 months. Second-line therapy with nivolumab and trastuzumab/pertuzumab was well-tolerated, with macroscopic peritoneal response. Following ovarian progression and surgical resection of ovarian metastases, immunohistochemistry of PD-L1 was negative; proteomics demonstrated normal expression of HER2 and absence of PD-L1, while genomics showed HER2 amplification, suggesting mechanisms of escape to dual HER2 blockade by downregulation of HER2 and to nivolumab by the absence of PD-L1. Based upon this and nonexpression of biomarkers of taxane resistance, therapy was changed to paclitaxel. Two and a half years after diagnosis, the patient is undergoing treatment, with excellent performance status. CONCLUSIONS: Molecular analysis and personalized therapy can help optimize treatment in difficult-to-treat cancers.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linitis Plástica/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Estómago/efectos de los fármacos , Femenino , Humanos , Linitis Plástica/metabolismo , Persona de Mediana Edad , Medicina de Precisión/métodos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismoAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neumonía en Organización Criptogénica/inducido químicamente , Progresión de la Enfermedad , Neoplasias Pulmonares/tratamiento farmacológico , Neumonía en Organización Criptogénica/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , NivolumabRESUMEN
Novel immunotherapy approaches have provided durable remission in a significant number of cancer patients with cancers previously considered rapidly lethal. Nonetheless, the high degree of nonresponders, and in some cases the emergence of resistance in patients who do initially respond, represents a significant challenge in the field of cancer immunotherapy. These issues prompt much more extensive studies to better understand how cancer cells escape immune surveillance and resist immune attacks. Here, we review the current knowledge of how cellular heterogeneity and plasticity could be involved in shaping the tumor microenvironment (TME) and in controlling antitumor immunity. Indeed, recent findings have led to increased interest in the mechanisms by which cancer cells undergoing epithelial-mesenchymal transition (EMT), or oscillating within the EMT spectrum, might contribute to immune escape through multiple routes. This includes shaping of the TME and decreased susceptibility to immune effector cells. Although much remains to be learned on the mechanisms at play, cancer cell clones with mesenchymal features emerging from the TME seem to be primed to face immune attacks by specialized killer cells of the immune system, the natural killer cells, and the cytotoxic T lymphocytes. Recent studies investigating patient tumors have suggested EMT as a candidate predictive marker to be explored for immunotherapy outcome. Promising data also exist on the potential utility of targeting these cancer cell populations to at least partly overcome such resistance. Research is now underway which may lead to considerable progress in optimization of treatments.
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Transición Epitelial-Mesenquimal/inmunología , Neoplasias/inmunología , Escape del Tumor , Microambiente Tumoral/inmunología , Animales , Humanos , Neoplasias/patologíaRESUMEN
Scopulariopsis brevicaulis onychomycosis with local cutaneous invasion was diagnosed in an acute leukemia patient and unsuccessfully treated with high-dose micafungin, based on antifungal susceptibility testing. This case should alert clinicians to the possible severe evolution of onychomycosis in neutropenic patients and suggests that surgery should be preferred in such a situation.
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Equinocandinas/uso terapéutico , Dermatosis del Pie/tratamiento farmacológico , Huésped Inmunocomprometido , Lipopéptidos/uso terapéutico , Neutropenia/complicaciones , Onicomicosis/complicaciones , Onicomicosis/tratamiento farmacológico , Scopulariopsis/fisiología , Anciano , Antifúngicos/uso terapéutico , Dermatomicosis/complicaciones , Dermatomicosis/diagnóstico , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/inmunología , Femenino , Dermatosis del Pie/complicaciones , Dermatosis del Pie/diagnóstico , Dermatosis del Pie/inmunología , Humanos , Micafungina , Neutropenia/inmunología , Onicomicosis/diagnóstico , Onicomicosis/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: The identification of molecular mechanisms conferring resistance to tyrosine kinase inhibitor (TKI) is a key step to improve therapeutic results for patients with oncogene addiction. Several alterations leading to EGFR and anaplastic lymphoma kinase (ALK) resistance to TKI therapy have been described in non-small cell lung cancer (NSCLC). Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far. METHODS: A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib. Molecular analysis (whole-exome sequencing, CGH) and functional studies were undertaken to elucidate the mechanism of resistance. Based on this case, we took advantage of the structural homology of ROS1 and ALK to build a predictive model for drug sensitivity regarding future ROS1 mutations. RESULTS: Sequencing revealed a dual mutation, S1986Y and S1986F, in the ROS1 kinase domain. Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922). The patient's clinical response confirmed the potency of lorlatinib against S1986Y/F mutations. The ROS1 S1986Y/F and ALK C1156Y mutations are homologous and displayed similar sensitivity patterns to ALK/ROS1 TKIs. We extended this analogy to build a model predicting TKI efficacy against potential ROS1 mutations. CONCLUSIONS: Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib. Clin Cancer Res; 22(24); 5983-91. ©2016 AACR.
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Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/genética , Aminopiridinas , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Crizotinib , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Lactamas , Lactamas Macrocíclicas/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación/efectos de los fármacos , Mutación/genética , Proteínas de Fusión Oncogénica/genética , Pirimidinas/uso terapéutico , Sulfonas/uso terapéuticoRESUMEN
BACKGROUND: Drugs targeting programmed death receptor-1 (PD-1) and its ligand PD-L1 have shown activity in multiple malignancies. Considering their novel mechanism of action, whether traditional prognostic scores also apply to patients treated with these drugs is unknown. We investigated whether a baseline 3-point (pt) computed tomography (CT) scan (PS3-CT) score and a 7-pt prognostic (PS7) score allowed identifying long-term survivors on anti-PD-1/-L1 therapy. MATERIALS AND METHODS: We reviewed 251 consecutive patients enrolled in phase I trials evaluating anti-PD-1/-L1 agents between 26th December 2011 and 7th September 2015. PS3-CT was calculated using high tumour burden (TB1D-RECIST > 9 cm), low skeletal muscle index (SMI < 53 cm(2) m(-2)) and non-pulmonary visceral metastases (NPVM) (1 pt each). PS7 was calculated by adding lower performance status, decreased serum albumin, increased serum lactate dehydrogenase and more than two distant metastases (1 pt each). Effect on overall survival (OS) of each parameter was tested using Kaplan-Meier and multivariable Cox analyses. RESULTS: PS3-CT was a significant independent predictor of OS (hazard ratio [HR] = 1.39 [95% confidence interval {CI} = 1.07-1.81], p = 0.01) when compared to the Royal Marsden Hospital, Barbot and American Joint Committee on Cancer scores. High TB (n = 78), low SMI (n = 55) and NPVM (n = 146) were associated with poorer survival (p < 0.01). High TB and low SMI were independent predictors of OS (respective HR of death: 2.00 [95% CI = 1.38-2.88], p < 0.01 and 1.75 [95% CI = 1.15-2.66], p < 0.01). PS7 was a significant predictor of OS (HR = 1.40 [95% CI = 1.25-1.56], p < 0.01). CONCLUSION: Objective and rapid-risk scoring based on three CT scan parameters allows identifying patients with prolonged OS on anti-PD-1/-L1 therapy, independently from conventional clinical-biological prognostic scores.
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Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias Primarias Múltiples/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/patología , Pronóstico , Modelos de Riesgos Proporcionales , Criterios de Evaluación de Respuesta en Tumores Sólidos , Adulto JovenRESUMEN
INTRODUCTION: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in whites and Asians. However, little information addresses the underlying genetic changes among Caribbean and African Caribbean patients. In this study, we identified targetable biomarkers in Caribbean patients with lung adenocarcinoma. METHODS: DNA extracted from lung adenocarcinoma specimens collected from 157 patients in whom primary lung adenocarcinoma was diagnosed from 2013 to 2015 in the University Hospital of Martinique was tested for mutation of the epidermal growth factor receptor gene (EGFR), Kirsten rat sarcoma viral oncogene homolog gene (KRAS), B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS), and MMNG HOS Transforming gene (MET). Clinical characteristics of our patients have been retrospectively gathered and correlated with mutational status. RESULTS: Mutations in EGFR were identified in 57 cases (36%). Women accounted for 68% of patients with mutations versus 38% of those without mutations (p < 0.001). Eighteen percent of patients with mutations were smokers versus 62% of patients without mutations (p < 0.001). Sex, smoking habit, and age were significantly associated with differences in mutational status in univariate analysis, and the difference remained statistically significant in multivariate analysis (p = 0.0411, p = 0.001, and p = 0.0483, respectively). After the analysis was restricted to patients born in the French West Indies, the mutation rates reached 41%. CONCLUSION: Patients in Martinique, and specifically those of African descent, show very high levels of EGFR mutation as opposed to what can be found in mainland France or in African Americans. These findings may be ascribed to low tobacco consumption as well as to genetic factors. Systematic screening in patients of African Caribbean origin should be prescribed.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Región del Caribe/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Proto-Oncogenes Mas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
During the past decade, the treatment of lung adenocarcinomas has been revolutionized with novel molecular targeted therapies. We describe a case of clinical activity of crizotinib in a female patient with a lung adenocarcinoma displaying a MET exon 14 donor splice site mutation (D1028N) detected using next generation sequencing. Within 5 weeks of crizotinib therapy, a partial response was observed in this 67 year-old woman. Further clinical trials of crizotinib are needed for non-small cell lung cancer exhibiting MET mutations.