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OBJECTIVE: The aim of this study was to confirm the relationship between several parameters of exposure to asbestos and pleural plaques (PP) using data from a large cohort of retired workers occupationally exposed to asbestos in France. METHOD: A large screening programme, including high-resolution CT (HRCT) examinations at inclusion and two other HRCT campaigns, was organised from 2003 to 2016 in four regions of France for voluntary, formerly asbestos-exposed workers. Exposure to asbestos has been evaluated by industrial hygienists based on the complete work history. The time since first exposure, the time since last exposure, Cumulative Exposure Index and maximum level of exposure to asbestos, were used in logistic regression using fractional polynomials to model the relationship with PP. RESULTS: The study included 5392 subjects with at least one HRCT available. There was a significant non-linear effect of time since first exposure, time since last exposure and Cumulative Exposure Index to asbestos on the presence of PP. The risk of PP increased with increasing Cumulative Exposure Index to asbestos adjusted for time since first exposure, age and smoking status. Models also show that PP odds rise with increasing time since first exposure adjusted for cumulative index exposure, age and smoking status. PP odds decrease when time since last exposure increases. CONCLUSION: The study provides new data on the link between asbestos exposure and the presence of PP using fractional polynomials with non-linear relationships for time exposure parameters and asbestos exposure parameters.
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Amianto , Exposição Ocupacional , Doenças Pleurais , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Masculino , França/epidemiologia , Pessoa de Meia-Idade , Idoso , Feminino , Doenças Pleurais/epidemiologia , Doenças Pleurais/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Estudos de Coortes , Asbestose/etiologia , Modelos LogísticosRESUMO
PURPOSE: This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations. METHODS: In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic). RESULTS: The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis. CONCLUSIONS: Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.
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Fator Estimulador de Colônias de Granulócitos , Padrões de Prática Médica , Humanos , Estudos Transversais , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Inquéritos e Questionários , Pessoa de Meia-Idade , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Assistência Ambulatorial/métodos , Neoplasias/tratamento farmacológico , Pacientes Ambulatoriais/estatística & dados numéricosRESUMO
BACKGROUND: Few studies of the under-representation of older adults in cancer clinical trials (CTs) have encompassed the entire pathway from a trial being available in a cancer centre to the patient's invitation to participate and then agreement or refusal to participate. OBJECTIVES: The study's primary objective was to evaluate CT non-invitation and refusal rates. The secondary objectives were to identify factors associated with non-invitation and refusal and to assess experiences of CT participation from the patients' and professionals' perspectives. METHODS: Here, we used mixed methods and a socio-epidemiological approach to analyse reasons for the non-participation of eligible older patients with a solid cancer in cancer CTs in France. RESULTS: We found that non-invitation and low CT participation are mainly related to the patients' sociodemographic characteristics and living conditions (such as social isolation, being single, divorced or widowed, not having children and the absence of close family members) and the healthcare professionals' perceptions of insufficient informal support or a high homecare requirement. CONCLUSION: Our results suggest that efforts to increase fair inclusion and the participation of older adults in CTs should target the physician-patient relationship, the medical profession and hospital funding, rather than the patient alone.
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Neoplasias , Humanos , Idoso , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Relações Médico-Paciente , França/epidemiologiaRESUMO
Anti-PD-1/PD-L1 plus chemotherapy (CT) is considered the standard of care in first line treatment of metastatic NSCLC. However, the clinical benefit of this combination in older patients is controversial. We performed a meta-analysis of phase III randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for older patients with advanced NSCLC. Subgroups of patients over 65 and over 75 were analyzed. The outcomes included overall survival (OS) and progression-free survival (PFS). A fixedeffect model was used. We analyzed ten trials with an anti-PD-1 (camrelizumab, cemiplimab, nivolumab, pembrolizumab, tislelizumab or toripalimab) and six trials with an anti-PD-L1 (atezolizumab, durvalumab or sugemalimab), including 3666 patients over the age of 65 (41%) and 282 patients over the age of 75 (<10%). For patients over 65 years of age, anti-PD- 1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.79 [0.72-0.86]; p < 0.00001) and P FS (0.63 [0.58-0.68]; p < 0.00001) compared to CT alone. Survival benefits occurred in both anti-PD-1 and anti-PD-L1 trials. For patients over 75 years of age, OS benefit was not statistically significant (0.88 [0.67-1.16]; p = 0.37). For patients over the age of 65 with untreated NSCLC, the anti-PD-1/PD-L1 combination with CT, compared with CT alone, is associated with significantly improved OS and PFS. Due to the low number of patients, it is difficult to conclude for those over 75.
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BACKGROUND: An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs. OBJECTIVE: This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients. METHODS: The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs. RESULTS: Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (n = 17), lung (n = 12), digestive (n = 9) and breast cancer (n = 9). Reimbursement costs for EA treatments surged from 42 to 526 million (+ 1159%). CONCLUSION: The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.
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Antineoplásicos , Aprovação de Drogas , Neoplasias , França , Humanos , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Estudos Retrospectivos , Neoplasias/tratamento farmacológico , Estudos Longitudinais , Oncologia/economia , Acessibilidade aos Serviços de Saúde , Custos de MedicamentosRESUMO
Antibody-drug conjugates (ADCs) are an emerging class of therapeutics for lung cancer, and several are currently in development for this malignancy. The structure of these molecules is based on an antibody that targets a protein on the lung cancer cell surface and a cytotoxic payload attached by a linker. Many protein targets, including TROP2, c-MET, CEACAM5, HER2, and HER3 have been identified. In metastatic non-small cell lung carcinoma (NSCLC) without alterations in oncogenic drivers, platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death-ligand 1 (PD1/PDL1) interaction are the standard first-line treatments. In patients with EGFR-mutated or ALK-rearranged NSCLC, tyrosine kinase inhibitors (TKIs) are recommended. However, although the prognosis of patients with metastatic NSCLC differs between such with and without alterations in oncogenic drivers, most patients eventually experience disease progression. A novel therapeutic class is needed in routine practice to overcome the mechanisms of resistance to ICIs and EGFR/ALK TKIs. Several ADCs have already been approved for other cancers, such as breast cancer and urothelial carcinoma. This review summarizes the knowledge about the efficacy and tolerance profiles of ADCs targeting TROP2, HER2, HER3, CEACAM5 and c-MET in metastatic NSCLC with and without alterations in oncogenic drivers.
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Carcinoma Pulmonar de Células não Pequenas , Imunoconjugados , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Terapia de Alvo MolecularRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have become standard-of-care at different stage disease in non-small cell lung cancer (NSCLC). Based on the increasing characterization of molecular aberrations and oncogenic drivers in NSCLC, it is expected that more and more patients will benefit from orally small targeted therapies in NSCLC. However, their concomitant or sequential use is associated with an increased risk of a various toxicity pattern. METHODS: Relevant publications were included if they reported data on the question of toxicities associated with sequential or combined use of ICIs and small targeted therapies used in NSCLC treatment. MEDLINE, Google Scholar, and the Cochrane Library were searched for the following request, from database inception until June 2023. RESULTS: This review highlighted a various pattern of toxicities (i.e., interstitial lung disease, hepatitis, dermatoses) in the context of both sequential and concomitant administration of ICIs and small targeted therapies. Such toxicities seem rather a "drug-effect" than a "class-effect" and some of these toxicities are more specific of a small targeted therapy. This review highlights on the impact of treatment sequence administration and emphasis for physicians to be particularly careful whether small targeted therapy is administered within one to three months after last ICIs injection. CONCLUSION: Physicians have to be aware of severe toxicities in case of both concomitant or sequential ICIs/small targeted therapies administration in NSCLC. Further studies are needed to better understand the mechanisms underlying these toxicities in order to prevent them and to refine ICIs and small targeted therapy sequencing strategy.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Objectives: We investigated the mortality patterns of chronic obstructive pulmonary disease (COPD) patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods: COPD patient and sex, age and residence matched control cohorts were created from the French National Health Data System. Survival was analyzed using Cox regressions and standardized rates. Results: All-cause mortality increased in 2020 compared to 2019 in the COPD population (+4%), but to a lesser extent than in the control population (+10%). Non-COVID-19 mortality decreased to a greater extent in COPD patients (-5%) than in the controls (-2%). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs. 279 per 100,000 person-years). Conclusion: The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing.
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COVID-19 , Doença Pulmonar Obstrutiva Crônica , Humanos , COVID-19/epidemiologia , Pandemias , França/epidemiologia , Distribuição por IdadeRESUMO
INTRODUCTION: A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest. METHODS: We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation. RESULTS: Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFRL858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; p < 0.0001) and OS (HR: 0.69 [0.52-0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; p < 0.00001). CONCLUSIONS: For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination. REGISTRATION: PROSPERO CRD42024508055.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Ensaios Clínicos Fase III como Assunto , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Taxa de SobrevidaRESUMO
Background: Biomarkers to identify lung cancer (LC) patients with high risk of venous thromboembolism (VTE) are needed. Objectives: To evaluate the usefulness of plasma tissue factor activity (TFA) and D-dimer levels for the prediction of VTE and overall survival in patients with LC. Methods: In a prospective multicenter observational cohort of consecutive LC patients, TFA and D-dimer levels were measured at diagnosis before any cancer treatment (V1) and between 8 and 12 weeks after diagnosis (V2). Results: Among 302 patients, 38 (12.6%) experienced VTE within the first year after diagnosis. V1-TFA and V1-D-dimer levels were significantly (P = .02) higher in patients who presented VTE within 3 months than in patients without VTE: V1-TFA was 2.02 (25th-75th percentiles, 0.20-4.01) vs 0.49 (0.20-3.09) ng/mL and V1-D-dimer was 1.42 (0.64-4.40) vs 0.69 (0.39-1.53) µg/mL, respectively. Cutoffs of 1.92 ng/mL for TFA and 1.26 µg/mL for D-dimer could discriminate both groups of patients. In multivariate analysis, V1-TFA > 1.92 ng/mL was the only significant predictor of VTE risk at 1 year (hazard ratio, 2.10; 95% CI, 1.06-4.16; P = .03). V2-TFA, quantified in 251 patients, decreased significantly compared with V1-TFA (0.20 vs 0.56 ng/mL, P < .05), but a V2-TFA level > 0.77 ng/mL could predict VTE in the following 3 months. Median overall survival was worse for patients with V1-TFA > 1.92 ng/mL (14.6 vs 23.8 months) and V1-D-dimer > 1.26 µg/mL (13.8 vs 24 months, P < .001). Conclusion: High plasma TFA levels are associated with the occurrence of VTE within the next 3 months after each visit (V1 or V2) and poor survival.
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Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Little is known about immune checkpoint inhibitor activity in the central nervous system, especially in patients receiving monotherapy for tumors with a tumor proportion score (TPS) ≥ 50%. This noninterventional, retrospective, multicenter study, conducted with the GFPC, included treatment-naïve patients strongly positive for PD-L1 (TPS ≥ 50%) with BM receiving first-line single-agent pembrolizumab treatment between May 2017 and November 2019. The primary endpoints were centrally reviewed intracranial overall response rates (ORRs), centrally reviewed intracranial progression-free survival (cPFS), extracranial PFS, and overall survival were secondary endpoints. Forty-three patients from five centers were included. Surgical or local radiation therapy was administered to 31 (72%) patients, mostly before initiating ICI therapy (25/31). Among 38/43 (88.4%) evaluable patients, the intracranial ORR was 73%. The median PFS was 8.3 months. The cerebral and extracerebral median PFS times were 9.2 and 5.3 months, respectively. The median OS was 25.5 months. According to multivariate analysis, BM surgery before ICI therapy was the only factor significantly associated with both improved PFS (HR = 0.44) and OS (HR = 0.45). This study revealed the feasibility and outcome of front-line pembrolizumab treatment in this population with BM.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêuticoRESUMO
Purpose: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is an effective first-line therapy for patients with common EGFR mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary EGFR mutations is implicated as a resistance mechanism. This study describes patients with NSCLC who acquired the rare EGFR mutations, L718Q or G724S, following EGFR TKI treatment. Patients and Methods: This was a retrospective, observational study undertaken in France from Feb-Nov 2021, in patients with EGFR mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment. Results: Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6-31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1-31.7 months. Two of these patients had previously received osimertinib. Conclusion: Currently, there is no consensus regarding the treatment of EGFR mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.
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INTRODUCTION: In France, 40% of patients diagnosed with lung cancer are ≥70 years old, but these are under-represented in clinical trials. Using data from the French Epidemiological Strategy and Medical Economics (ESME) platform on Lung Cancer (LC), the objective is to provide an overview of the management and the prognosis of older patients with advanced or metastatic non-small cell lung cancer (AM-NSCLC) in a real-world context. MATERIALS AND METHODS: From the ESME-LC database, we selected patients with AM-NSCLC (stage IIIB, IIIC, and IV), diagnosed between 2015 and 2019, and who received first-line systemic treatment. Demographics, tumour characteristics, and treatment received were described in patients ≥70, and compared to younger ones. Real-world progression-free survival (rwPFS) and overall survival (OS) were evaluated using the multivariable Cox model. RESULTS: Among 10,002 patients with AM-NSCLC, the median age was 64 years, with 2,754 (27.5%) aged ≥70. In comparison with patients <70, older patients were more often male, with worse performance status and more comorbidities, but they were less underweight and more often non-smokers. The proportion of EGFR mutated non-squamous NSCLC was higher in older patients (25.0% vs 12.8%, p < 0.001), particularly among smokers and former smokers (12.7% vs 7.3%, p < 0.001). Among patients ≥70, 76.6% received first-line chemotherapy (including 67.0% treated with a platinum-based doublet), 15.0% received only targeted therapy, and 11.0% received immunotherapy (alone or in combination). Median first-line rwPFS was 5.1 months (95% confidence interval [CI] = [4.8;5.4]) for patients ≥70 and 4.6 months (95%CI = [4.4;4.8]) for patients <70, but age was not associated with rwPFS in multivariable analysis. Median OS was 14.8 months (95%CI = [13.9;16.1]) for patients ≥70 and 16.7 months (95%CI = [15.9;17.5]) for patients <70, with a significant effect of age in multivariable analysis for patients treated with chemotherapy and/or with targeted therapy, but not for patients treated with immunotherapy (alone or in combination with chemotherapy). DISCUSSION: In this real-world cohort of patients with AM-NSCLC, age was not associated with first-line rwPFS regardless of treatment received, nor with OS for patients receiving immunotherapy. However, OS was significantly shorter for patients aged ≥70 treated with chemotherapy or with targeted therapy alone.
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Background: Few epidemiological data are available on surgically treated Caucasian patients with non-small-cell lung cancers (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations. The main objective of this study was to describe, in the real-world setting, these patients' incidence, clinical, and tumoral characteristics. Methods: The participating centers included all consecutive localized non-squamous NSCLC patients undergoing surgery between January 2018 and December 2019 in France. EGFR status was determined retrospectively when not available before surgery. Results: The study includes 1391 no squamous NSCLC patients from 16 centers; EGFR status was determined before surgery in 692 (49.7%) of the cases and conducted as part of the study for 699 (50.3%); 171 (12.3%) were EGFR mutated; median age: 70 (range: 36-88) years; female: 59.6%; never smokers: 75.7%; non-squamous histology 97.7%, programmed death ligand-1 expression 0%/1-49%/⩾50 in 60.5%/25.7%/13.8%, respectively. Surgery was predominantly lobectomy (81%) or segmentectomy (14.9%), with systematic lymph node dissection in 95.9%. Resection completeness was R0 for 97%. Post-surgery staging was as follows: IA: 52%, IB: 16%, IIA: 4%, IIB: 10%, IIIA: 16%, and IIIB: 0.05%; EGFR mutation exon was Del19/exon 21 (L858R)/20/18 in 37.4%/36.8%/14%, and 6.4% of cases, respectively; 31 (18%) patients received adjuvant treatment (chemotherapy: 93%, EGFR tyrosine kinase inhibitor: 0%, radiotherapy: 20%). After a median follow-up of 31 (95% confidence interval: 29.6-33.1) months, 45 (26%) patients relapsed: 11/45 (24%) locally and 34 (76%) with metastatic progression. Median disease-free survival (DFS) and overall survival were not reached and 3-year DFS was 60%. Conclusion: This real-world analysis provides the incidence and outcomes of resected EGFR-mutated NSCLCs in a European patient cohort.
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BACKGROUND: In an open-label multicenter non-randomized non-comparative phase II study in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC), oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine-kinase inhibitor and no prior chemotherapy (NCT04042558), atezolizumab, carboplatin, pemetrexed with or without bevacizumab showed some promising result. Beyond the clinical evaluation, we assessed safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in this population. MATERIALS: Patients received platinum-pemetrexed-atezolizumab-bevacizumab (PPAB cohort) or, if not eligible, platinum-pemetrexed-atezolizumab (PPA cohort). The incidence, nature, and severity of adverse events (AEs) were assessed. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-Core 30 and EORTC QLQ-Lung Cancer 13). RESULT: Overall, 68 (PPAB) and 72 (PPA) patients were evaluable for safety. Grade 3-4 AEs occurred in 83.8% (PPAB) and 63.9% (PPA). Grade 3-4 atezolizumab-related AEs occurred in 29.4% and 19.4%, respectively. Grade 3-4 bevacizumab-related AEs occurred in 36.8% (PPAB). Most frequent grade 3-4 AEs were neutropenia (19.1% in PPAB; 23.6% in PPA) and asthenia (16.2% in PPAB; 9.7% in PPA). In PPAB, we observed a global stability in global health security (GHS) score, fatigue and dyspnea with a constant tendency of improvement, and a significant improvement in cough. In PPA, we observed a significant improvement in GHS score with a significant improvement in fatigue, dyspnea and cough. At week 54, we observed an improvement from baseline in GHS score for 49.2% of patients. In both cohorts, patients reported on average no clinically significant worsening in their overall health or physical functioning scores. CONCLUSION: PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR mutation or ALK/ROS1 fusion) after targeted therapies.
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Quinase do Linfoma Anaplásico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Estadiamento de Neoplasias , Medidas de Resultados Relatados pelo Paciente , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores ErbB/genética , Quinase do Linfoma Anaplásico/genética , Pessoa de Meia-Idade , Idoso , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso de 80 Anos ou mais , Terapia de Alvo Molecular , Proteínas de Fusão Oncogênica/genética , Progressão da Doença , Qualidade de VidaRESUMO
BACKGROUND: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results. METHODS: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety. RESULTS: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related. CONCLUSIONS: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ipilimumab , Nivolumabe , Neoplasias Pleurais , Humanos , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Ipilimumab/administração & dosagem , Ipilimumab/uso terapêutico , Ipilimumab/efeitos adversos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/patologia , Adulto , Taxa de Sobrevida , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND: Management of stage-III-N2 non-small-cell lung cancer (NSCLC) based on a multimodal strategy (surgery or radiotherapycombined with systemic drugs) remains controversial. Patients are treated with a curative intent, and available data suggestprolonged survival after complete resection. However, no consensual definition of "tumor resectability" exists. This study aimed to analyze the concordanceamong French tumor board meeting (TBM)-emittedtherapeutic decisions forstage-III-N2 NSCLC. METHODS: Six patients with stage-III-N2 NSCLC discussed at Saint-Etienne University Hospital'sthoracic TBMs were selected, anonymouslyreported, and submitted to the participating TBMs. The primary goal of this multicenter, prospective, observational study was to assess the consistency of TBMpanel decisions for each case. The secondary endpointwas identifying the demographic or technical factors that potentiallyaffected decision-making. RESULTS: Twenty-seven TBMs from university hospitals, a cancer center, general hospitals, and a private hospitalparticipated in this study. None of their decisions for the six cases were unanimous.The decisions were homogenous for three cases (78%, 85%, and 88% TBMs opted for medical treatment, respectively),andmore ambivalent for the other three (medical versus surgical strategies were favored by 44%/56%, 46%/54%, and 58%/42% TBMs, respectively). Interestingly, decisions regarding chemoradiationand perioperative chemotherapyinthe medical and surgical strategies, respectively, were also discordant. Hospital type, specialist participation in TBMs, and activity volumes were not significantly associated with therapeutic decisions. CONCLUSION: The results of this study highlight substantial disparities amongFrench TBMs regarding therapeutic management of stage-III-N2 NSCLC. The decisions were not associated with local conditions.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Gerenciamento Clínico , Terapia Combinada , Pneumonectomia , Tomada de Decisão ClínicaRESUMO
Most patients with lung cancer are smokers and are of advanced age. They are therefore at high risk of having age- and lifestyle-related comorbidities. These comorbidities are subject to treatment or even polypharmacy. There is growing evidence of a link between lung cancer, comorbidities and medications. The relationships between these entities are complex. The presence of comorbidities and their treatments influence the time of cancer diagnosis, as well as the diagnostic and treatment strategy. On the other hand, cancer treatment may have an impact on the patient's comorbidities such as renal failure, pneumonitis or endocrinopathies. This review highlights how some comorbidities may have an impact on lung cancer presentation and may require treatment adjustments. Reciprocal influences between the treatment of comorbidities and anticancer therapy will also be discussed.