El cáncer de pulmón en mujeres

Lung cancer is the most frequent malignant disease in the world. Over the last ten years lung cancer mortality has risen in Spain by 20% among women compared with 5% among men. This is due to recent changes in both genders’ smoking habits. Tobacco is still the single most important cause of a preventable disease in a high percentage of cases. It is extremely important that the population is aware of this and that people modify their lifestyle accordingly, giving up smoking in order to halt the lung cancer epidemic. In this article, we review epidemiological aspects, as well as risk factors, characteristics and the prognosis for women with lung cancer, focusing particularly on the Spanish population.El cáncer de pulmón es la enfermedad maligna más frecuente en el mundo. En los últimos diez años en España, la mortalidad por cáncer de pulmón ha aumentado un 20% en las mujeres frente a un 5% en los hombres, debido a los cambios recientes de patrones de hábito tabáquico entre ambos sexos. El tabaco sigue siendo la causa única más importante de una enfermedad prevenible en un alto porcentaje de casos. Es muy importante que la población conozca esta realidad y que modifique el estilo de vida, eliminado el tabaquismo, para poder detener esta epidemia que representa el cáncer de pulmón. En este artículo se revisarán aspectos epidemiológicos, así como factores de riesgo, características y pronóstico de las mujeres con cáncer de pulmón, con una especial atención a la población española

El cáncer de pulmón en mujeres

Lung cancer is the most frequent malignant disease in the world. Over the last ten years lung cancer mortality has risen in Spain by 20% among women compared with 5% among men. This is due to recent changes in both genders’ smoking habits. Tobacco is still the single most important cause of a preventable disease in a high percentage of cases. It is extremely important that the population is aware of this and that people modify their lifestyle accordingly, giving up smoking in order to halt the lung cancer epidemic. In this article, we review epidemiological aspects, as well as risk factors, characteristics and the prognosis for women with lung cancer, focusing particularly on the Spanish population.<br><br>El cáncer de pulmón es la enfermedad maligna más frecuente en el mundo. En los últimos diez años en España, la mortalidad por cáncer de pulmón ha aumentado un 20% en las mujeres frente a un 5% en los hombres, debido a los cambios recientes de patrones de hábito tabáquico entre ambos sexos. El tabaco sigue siendo la causa única más importante de una enfermedad prevenible en un alto porcentaje de casos. Es muy importante que la población conozca esta realidad y que modifique el estilo de vida, eliminado el tabaquismo, para poder detener esta epidemia que representa el cáncer de pulmón. En este artículo se revisarán aspectos epidemiológicos, así como factores de riesgo, características y pronóstico de las mujeres con cáncer de pulmón, con una especial atención a la población española

First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers

PURPOSE: To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study. METHODS: In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability-high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter. RESULTS: In phase 1, 58 patients received cetrelimab. Two dose-limiting toxicities were reported and two recommended phase 2 doses (RP2D) were defined (240 mg Q2W or 480 mg Q4W). After a first dose, mean maximum serum concentrations (C CONCLUSIONS: The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors. TRIAL REGISTRATIONS: NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016-002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017

Editorial: Multidisciplinary management of cancer patients with immune-related adverse events from checkpoint inhibitors

Cancer; Immunotherapy; ToxicityCáncer; Inmunoterapia; ToxicidadCàncer; Immunoteràpia; Toxicita

Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer

Conflicts of Interest: AFD declares travel expenses from Roche, MSD and Novartis. EF declares a consulting and advisory role for Novartis; research funding from Pfizer and travel expenses from Lilly, Novartis and Pfizer. AP declares travel expenses from Roche and BMS. MM has participated as an advisor of Lilly, Seagen, Novartis, Pficer, Roche, and Kern; her institution has received re- search funding from Pfizer, Roche, Eisai, Astrazeneca and Kern and travel expenses from Gilead. MB declares no potential conflict of interest.Funding: This research received no external funding. EF is supported by a Rio Hortega grant from the Instituto de Salud Carlos III (ISCIII- CM20/00027).Despite the improvement achieved by the introduction of HER2-targeted therapy, up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T- DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown a significant improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). In ER+ HER2+ patients, target therapies such as phosphoinositide-3-kinase (PI3K) pathway inhibition or cyclin-dependent kinases 4/6 blocking may be effective in controlling downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies. Multiple trials have explored these strategies with some promising results, and probably, in the next years conclusive results will succeed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents such as HER-2 therapy plus checkpoint inhibitors, or new vaccines approaches have been investi-gated in this setting, with promising but controversial results obtained to date

Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study

Pembrolizumab; Non-small-cell lung cancerPembrolizumab; Cáncer de pulmón de células no pequeñasPembrolizumab; Càncer de pulmó de cèl·lules no petitesClinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680). Eligible patients with previously untreated metastatic nonsquamous non-small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator's choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Primary end points were overall survival (OS) and progression-free survival (PFS). Among 616 randomly assigned patients (n = 410, pembrolizumab plus pemetrexed-platinum; n = 206, placebo plus pemetrexed-platinum), median time from random assignment to data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) for OS was 0.60 (0.50 to 0.72) and PFS was 0.50 (0.42 to 0.60) for pembrolizumab plus platinum-pemetrexed versus placebo plus platinum-pemetrexed. 5-year OS rates were 19.4% versus 11.3%. Toxicity was manageable. Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%. Pembrolizumab plus pemetrexed-platinum maintained OS and PFS benefits versus placebo plus pemetrexed-platinum, regardless of programmed cell death ligand-1 expression. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations

Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management

INTRODUCTION The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population

Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial

Non-small-cell lung cancer; Predictive markersCàncer de pulmó de cèl·lules no petites; Marcadors predictiusCáncer de pulmón de células no pequeñas; Marcadores predictivosTumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)—an open-label, global, multicohort trial—evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted

The role of anti-EGFR therapies in EGFR-TKI-resistant advanced non-small cell lung cancer

Anti-EGFR; Biomarcador; Inhibidor de la tirosina quinasaAnti-EGFR; Biomarcador; Inhibidor de la tirosina quinasaAnti-EGFR; Biomarker; Tyrosine kinase inhibitorEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for the first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led to the development of second- and third-generation TKIs with improved clinical outcomes. However, sequential administration of TKIs has led to the emergence of new EGFR resistance mutations and persistent tumor cell survival. This evidence highlights the potential role of EGFR in transducing growth signals in NSCLC tumor cells. Therefore, dual inhibition of EGFR using combinations of anti-EGFR monoclonal antibodies (mAbs) and EGFR-TKIs may offer a unique treatment strategy to suppress tumor cell growth. Several clinical studies have demonstrated the benefits of dual blockade of EGFR using anti-EGFR mAbs coupled with EGFR-TKIs in overcoming treatment resistance in patients with EGFR-mutated NSCLC. However, a single treatment option may not result in the same clinical benefits in all patients with acquired resistance. Biomarkers, including EGFR overexpression, EGFR gene copy number, EGFR and KRAS mutations, and circulating tumor DNA, have been associated with improved clinical efficacy with anti-EGFR mAbs in patients with NSCLC and acquired resistance. Further investigation of biomarkers may allow patient selection for those who could benefit from anti-EGFR mAbs in combination with EGFR-TKIs. This review summarizes findings of recent studies of anti-EGFR mAbs in combination with EGFR-TKIs for the treatment of patients with EGFR-mutated NSCLC, as well as clinical evidence for potential biomarkers towards personalized targeted medicine