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BACKGROUND: We designed this study based on both a physician practice survey and real-world patient data to: (1) evaluate clinical management practices in extensive-stage small cell lung cancer (ES-SCLC) among medical centers located across France; and (2) describe first-line treatment patterns among patients with ES-SCLC following the introduction of immunotherapy into clinical practice. METHODS: A 50-item questionnaire was completed by physicians from 45 medical centers specialized in SCLC management. Responses were collected from June 2022 to January 2023. The survey questions addressed diagnostic workup of ES-SCLC, chemoimmunotherapy in first-line and second-line settings, and use of prophylactic cranial irradiation (PCI) and radiotherapy. In parallel, using a chart review approach, we retrospectively analyzed aggregated information from 548 adults with confirmed ES-SCLC receiving first-line treatment in the same centers. RESULTS: In ES-SCLC, treatment planning is based on chest computed tomography (CT) (as declared by 100% of surveyed centers). Mean time between diagnosis and treatment initiation was 2-7 days, as declared by 82% of centers. For detection of brain metastases, the most common imaging test was brain CT (84%). The main exclusion criteria for first-line immunotherapy in the centers were autoimmune disease (87%), corticosteroid therapy (69%), interstitial lung disease (69%), and performance status ≥ 2 (69%). Overall, 53% and 36% of centers considered that patients are chemotherapy-sensitive if they relapse within ≥ 3 months or ≥ 6 months after first-line chemoimmunotherapy, respectively. Among the 548 analyzed patients, 409 (75%) received chemoimmunotherapy as a first-line treatment, 374 (91%) of whom received carboplatin plus etoposide and 35 (9%) cisplatin plus etoposide. Overall, 340/548 patients (62%) received maintenance immunotherapy. Most patients (68%) did not receive radiotherapy or PCI. CONCLUSIONS: There is an overall alignment of practices reflecting recent clinical guidelines among medical centers managing ES-SCLC across France, and a high prescription rate of immunotherapy in the first-line setting.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Adulto , Humanos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Etoposídeo , Estudos Retrospectivos , Recidiva Local de Neoplasia , CarboplatinaRESUMO
BACKGROUND: Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation. METHODS: This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment. RESULTS: The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. < 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS. CONCLUSION: In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/etiologia , Encéfalo/patologiaRESUMO
BACKGROUND: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer. METHODS: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m2 from day 1 to day 3]) or oral topotecan (2·3 mg/m2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02738346. FINDINGS: Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0-37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9-5·5 vs 2·7 months, 2·3-3·2; stratified hazard ratio 0·57, 90% CI 0·41-0·73; p=0·0041). The most frequent grade 3-4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group. INTERPRETATION: Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer. FUNDING: Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie).
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Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Etoposídeo/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Topotecan/efeitos adversosRESUMO
OBJECTIVES: The aim of this study was to describe the characteristics of patients receiving bevacizumab plus first-line metastatic chemotherapy for non-squamous advanced non-small cell lung cancer (aNSCLC), with or without brain metastases, in routine clinical practice. Other objectives were to describe treatment efficacy, modalities of use, and safety. METHODS: For this non-interventional, prospective, national, multicentre study, data were collected every 3 months over 18 months. RESULTS: Of the 407 patients analysed, 84 (21%) with brain metastases at bevacizumab initiation had poorer general health than patients with no brain metastases (Eastern Cooperative Oncology Group [ECOG] performance status score = 2: 16 vs. 11%). All but 2 patients received bevacizumab (7.5 or 15 mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. Median progression-free survival and overall survival did not differ significantly between patients with or without brain metastases (6.5 months, 95% CI 5.7-8.1 vs. 6.9 months, 95% CI 5.9-7.6, p = 0.57; 14.5 months, 95% CI 10.0 vs. 12.5 months, 95% CI 10.1-14.7, p = 0.33). In 30 and 32% of the patients, respectively, at least one serious adverse event was reported, with a causal relationship to bevacizumab in 20 and 21% of the patients. CONCLUSION: This study confirmed in a real-life setting the safety profile and survival benefits of first-line chemotherapy with bevacizumab in aNSCLC patients with brain metastases.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Compostos Organoplatínicos/administração & dosagem , Estudos ProspectivosRESUMO
OBJECTIVES: The aim of this study was to describe the demographic and clinico-pathological characteristics of lung cancer in patients younger than 40 years. MATERIALS AND METHODS: This was a prospective study performed within the Groupe Français de Pneumo-Cancérologie. Consecutive patients diagnosed with lung cancer before the age of 40 years were eligible. Data on demographics, medical history, clinico-pathological characteristics, treatment and overall survival were analysed. RESULTS: In total, 146 patients were included from January 2011 to December 2013. Median age was 38 years (IQR: 34-40). Women accounted for 41%. Main histological type was adenocarcinoma (77%). Only 3% had a prior history of cancer, but a family history (first- or second-degree relatives) of cancer was reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall survival was 15.3 (95% CI: 8.1-24.0) months in the whole population, 10.3 (95% CI: 12.5-14.2) months in stage IV and 15 (95% CI: 8.7-35.2) months in stage III. One- and two-year overall survival rates were 57% (95 CI: 49-65) and 31.5% (95 CI: 27-43), respectively. Compared to smokers, non-smokers were significantly younger and more often females. Median overall survival was not statistically different between smokers and non-smokers.
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Neoplasias Pulmonares/epidemiologia , Adulto , Fatores Etários , Estudos de Coortes , Escolaridade , Emprego/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estudos Prospectivos , População Rural/estatística & dados numéricos , Fumar/epidemiologia , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Rash is a common epidermal growth factor receptor inhibitor-induced toxicity that can impair quality of life and treatment compliance. OBJECTIVE: We sought to evaluate the efficacy of doxycycline in preventing erlotinib-induced rash (folliculitis) in patients with non-small-cell lung cancer. METHODS: This open-label, randomized, prospective, phase II trial was conducted in 147 patients with locally advanced or metastatic non-small-cell lung cancer progressing after first-line chemotherapy, randomized for 4 months with erlotinib alone 150 mg/d per os (control arm) or combined with doxycycline 100 mg/d (doxycycline arm). Incidence and severity of rash, compliance, survival, and safety were assessed. RESULTS: Baseline characteristics of the 147 patients were well balanced in the intent-to-treat population. Folliculitis occurred in 71% of patients in the doxycycline arm and 81% in the control arm (P = .175). The severity of folliculitis and other skin lesions was lower in the doxycycline arm compared with the control arm. Other adverse events were reported at a similar frequency across arms. There was no significant difference in survival between treatment arms. LIMITATIONS: The open-label design of the study and the duration of the treatment with doxycycline are limitations. CONCLUSION: Doxycycline did not reduce the incidence of erlotinib-induced folliculitis, but significantly reduced its severity.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doxiciclina/uso terapêutico , Cloridrato de Erlotinib/efeitos adversos , Exantema/prevenção & controle , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Cloridrato de Erlotinib/uso terapêutico , Exantema/induzido quimicamente , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin-gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups. METHODS: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted. RESULTS: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 /QALY), in responders to induction chemotherapy (64,296 /QALY), regardless of histology (adenocarcinoma, 62,292 /QALY, non adenocarcinoma, 83,291 /QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 /QALY), in patients with adenocarcinoma (97,160 /QALY) and in patient with objective response to induction (101,186 /QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy. CONCLUSION: Gemcitabine- or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy.
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Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia de Indução/economia , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia de Manutenção/economia , Adulto , Idoso , Antineoplásicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Cisplatino/administração & dosagem , Cisplatino/economia , Análise Custo-Benefício , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Cloridrato de Erlotinib , Feminino , Custos de Cuidados de Saúde , Humanos , Neoplasias Pulmonares/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Quinazolinas/administração & dosagem , Quinazolinas/economia , Análise de Sobrevida , GencitabinaRESUMO
BACKGROUND: Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide. METHODS: We initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety. RESULTS: This study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer. CLINICAL TRIAL REGISTRATION: EU CT: 2023-504670-38-00.
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BACKGROUND: The KBP studies are real-life nationwide, prospective, multicenter cohort studies of patients diagnosed with primary lung cancer that have been conducted in French non-academic public hospitals each decade since 2000. METHODS: Patients were analyzed in three prospective cohorts using the same methodology. In this study, we describe and compare the characteristics and outcomes of patients with small cell lung cancer (SCLC), with a focus on treatments in the 2020 cohort. FINDINGS: 8999 patients with lung cancer were included in the 2020 cohort, of whom 1137 had SCLC. From 2000 to 2010 and 2020, the proportion of patients with SCLC decreased from 16.4 % to 13.5 % and 12.6 % respectively. Between 2000 and 2020, the proportion of women increased from 15.5 % to 35.7 %. 15.4 % of patients with SCLC had limited-stage (LS) disease and 84.6 % of patients had extensive-stage (ES) disease. The 1-year overall survival (OS) rate for all patients with SCLC increased from 34.4 % in 2000 to 38.4 % in 2020. For ES-SCLC, multivariate analysis weighted with "entropy balancing" by including age, sex, performance status, number of metastatic sites, and brain metastases indicated an improvement in median OS from 8.1 months in patients receiving chemotherapy only to 11.1 months in patients receiving chemotherapy plus immunotherapy (HR 0.62, p < 0.001). INTERPRETATION: The proportion with SCLC has decreased over time, but the proportion of women has increased. The 1-year OS rates have improved over 20 years. The KBP-2020 cohort suggests a benefit of immunotherapy on OS in patients with ES-SCLC in the real-life setting.
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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: 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.
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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
BACKGROUND: MET-targeted tyrosine kinase inhibitors (TKIs) demonstrated efficacy in advanced non-small cell lung cancer (aNSCLC) with MET exon14 skipping mutations (METexon14); yet, data on the management of these patients in clinical practice is sparse. OBJECTIVE: The aim of this study was to describe the management of METexon14 aNSCLC patients. PATIENTS AND METHODS: This real-life, retrospective study analyzed the management of METexon14 aNSCLC. The primary endpoint was the median overall survival (mOS). Secondary endpoints were to assess investigator-progression-free survival (PFS) and mOS in different subgroups: patients treated with (a) crizotinib, regardless of treatment line; (b) anti-MET TKIs (crizotinib, tepotinib, capmatinib); and (c) immunotherapy. RESULTS: A total of 118 patients were included between December 2015 and January 1, 2020 in 13 centers. Median age was 73 years, 62.7% were female, 83.9% had adenocarcinoma, 92.4% at stage IV, and 27% had more than three metastatic sites. The majority of the patients (106, 89.8%) received at least one systemic treatment; 73% received at least one anti-MET TKI: crizotinib (68.6%), tepotinib (16%), capmatinib (10%). Only 10% received two anti-MET TKIs in their treatment sequences. With a median follow-up of 16 months (95% CI 13.6-29.7), mOS was 27.1 months (95% CI 18-31.4). There was no significant difference between mOS of patients treated and never treated with crizotinib, 19.7 (95% CI 13.6-29.7) and 28 (95% CI 16.4-NR) months, respectively (p = 0.16); mOS of the TKI cohort and of the TKI-naïve patient cohort were 27.1 (95% CI 18-29.7) and 35.6 (95% CI 8.6-NR) months respectively, with no significant difference (p = 0.7). CONCLUSIONS: In this real-life study, there was no evidence of benefit in mOS with anti-MET TKIs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Masculino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Resultado do Tratamento , Mutação , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Outside clinical trials, few data are available on the effect of long-term first-line pembrolizumab in patients with advanced non-small-cell lung cancers with ≥50% of tumor cells expressing programmed cell death ligand 1 (PD-L1). This French, multicenter study included consecutive advanced patients with non-small-cell lung cancer given first-line pembrolizumab alone between May 2017 (authorization date for this indication) and November 2019 (authorization date for pembrolizumab-chemotherapy combination). Information was collected from patients' medical files, with a local evaluation of the response and progression-free survival (PFS). Overall survival (OS) was calculated from pembrolizumab onset using the Kaplan-Meier method. The analysis concerned 845 patients, managed in 33 centers: median age: 65 (range: 59-72) years, 67.8% men, 78.1% Eastern Cooperative Oncology Group performance status 0/1, 38.9%/51.5%/6.6% active, ex or never-smokers, respectively, 10.9%/16.8% taking or recently took corticosteroids/antibiotics, 69.6% nonsquamous histology, 48.9% ≥75% PD-L1-positive, and 20.8% had brain metastases at diagnosis. After a median (95% CI) follow-up of 45 (44.1-45.9) months, respective median (95% CI) PFS and OS lasted 8.2 (6.9-9.2) and 22 (8.5-25.9) months; 3-year PFS and OS rates were 25.4% and 39.4%, respectively. Multivariate analysis retained never-smoker status, adenocarcinoma histology, Eastern Cooperative Oncology Group performance status ≥2, and neutrophil/lymphocyte ratio >4 as being significantly associated with shorter survival, but not brain metastases at diagnosis or <75% PD-L1 tumor-cell expression. These long-term results of pembrolizumab efficacy based on a nationwide "real-world" cohort reproduced those obtained in clinical trials.
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BACKGROUND: Although ALK-translocated (ALK+) advanced non-small cell lung cancers (aNSCLCs) are currently treated with second- or third-generation ALK inhibitors (ALK-TKIs), some patients respond durably to the first-generation ALK-TKI crizotinib. OBJECTIVE: This study aimed to describe the clinical characteristics of these long-term responders. PATIENTS AND METHODS: This national, multicenter, retrospective, non-interventional study included patients with ALK+ aNSCLCs and long-term responses to first (L1)- or subsequent (≥ L2)-line crizotinib, defined, respectively, as treatments lasting > 18 and > 10 months. Median treatment duration (mDOT) was the primary endpoint. RESULTS: A total of 85 patients (32 L1 and 53 ≥ L2 responders) from 23 centers were included (receiving crizotinib between 10/24/2011-10/02/2018): median age of 59 years, 83.6% non-smokers or ex-smokers, 85.9% performance status (PS) 0/1, 94.1% with adenocarcinomas, median of one metastatic site, and 22.4% with brain metastases (BMs). After median follow-up of 73.4 [95% confidence interval, 67.5-79.9] months, respective L1 and ≥ L2 mDOTs were 43.3 [26.7-56.8] and 29.6 [22.6-35.8] months, with overall survival (OS) not reached (NR) and 116.2 [83.4-NR] months. BM presence or absence did not affect mDOT (31.4 versus 32.9 months) but significantly impacted median OS (70.6 versus 158.6 months; p = 0.0008). Progression on crizotinib was paucisymptomatic (74.1%) and oligometastatic (34.8%), especially BMs (42.4%). After crizotinib discontinuation, 65 (76.5%) patients received subsequent systemic therapy: 57 (67.1%) with second-generation ALK-TKIs. Respective mDOTs of first- and second-line post-crizotinib ALK-TKIs lasted 19.4 [14.9-25.6] and 11.1 [4.8-17.9] months, respectively. CONCLUSIONS: Most ALK+ aNSCLC patients with prolonged crizotinib efficacy had paucisymptomatic and oligometastatic disease without BMs. They subsequently benefited from a sequential strategy with other ALK-TKIs.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Quinase do Linfoma Anaplásico/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundárioRESUMO
BACKGROUND: Small cell lung cancer (SCLC) has a tendency towards recurrence and limited survival. Standard-of-care in 1st-line is platinum-etoposide chemotherapy plus atezolizumab or durvalumab,based on landmarkclinical trials. METHODS: IFCT-1905 CLINATEZO is a nationwide, non-interventional, retrospectivestudy of patients with extensive-SCLC receivingatezolizumab plus chemotherapy as part of French Early Access Program. Objectives were to analyse effectiveness,safetyand subsequent treatments. RESULTS: The population analyzed included 518 patients who received atezolizumabin 65 participating centers. There were 66.2% male,mean age was 65.7 years; 89.1% had a performance status (PS) 0/1 and 26.6% brain metastases. Almost all(95.9%) were smokers. Fifty-five (10.6%) received at least 1 previous treatment. Median number of atezolizumab injections was 7.0 (range [1.0-48.0]) for a median duration of 4.9 months (95% CI 4.5-5.1). Atezolizumab was continued beyond progression in 122 patients (23.6%) for a median duration of 1.9 months (95% CI: [1.4-2.3]). Best objective response was complete and partialin 19 (3.9%) and 378 (77.1%)patients. Stable diseasewas observed in 50 patients (10.2%). Median follow-up was30.8 months (95% CI: [29.9-31.5]). Median overall survival (OS), 12-, 24-month OS rates were 11.3 months (95% CI: [10.1-12.4]), 46.7% (95% CI [42.3-50.9]) and 21.2% (95% CI [17.7-24.8]). Median real-world progression-free survival, 6-, 12-month rates were 5.2 months (95% CI [5.0-5.4]), 37.5% (95% CI [33.3-41.7]) and 15.2% (95% CI [12.2-18.6]). For patients with PS 0/1, median OS was 12.2 months (95% CI [11.0-13.5]). For patients with previous treatment, median OS was 14.9 months (95% CI [10.1-21.5]). Three-hundred-and-twenty-six patients(66.4%) received subsequent treatment and27 (5.2%) were still underatezolizumabat date of last news. CONCLUSIONS: IFCT-1905 CLINATEZO shows reproductibility, in real-life,ofIMpower-133survival outcomes, possibly attributed to selection of patients fit for this regimen, adoption of pragmatic approaches,including concurrent radiotherapy and treatment beyond progression.
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OBJECTIVES: FRESC reanalyzed extensive-stage small-cell lung cancer (ES-SCLC) patient data from the French KBP-2010 cohort to describe the characteristics and therapeutic management of ES-SCLC and provide real-world estimates of survival. METHODS: A target population of first line (1L) ES-SCLC was identified at initial diagnosis in KBP-2010 (KBP population, N = 796). A KBP-2010 subpopulation was defined as patients who also met the IMpower133 clinicaltrial PS ≤ 1 inclusion criteria (KBP-PS_0/1 population, N = 394). Subgroups were defined according to the 1L ES-SCLC chemotherapy regimens: carboplatin or cisplatin with etoposide (Carb-E or Cisp-E subgroups). RESULTS: The vast majority of KBP populations exhibited stage IV ES-SCLC (84.9%) at initial diagnosis. Median age was 66 years; patients were mostly male and smokers. Patients receiving Cisp + Eto were younger (median age 61 years [55.0-67.0]) and fitter (25.5% had PS ≥ 2) than those receiving Carb + Eto (71 years [62.5-77.5]; 44.1%had PS ≥ 2). Median overall survival (OS) of chemotherapy-treated 1L ES-SCLC patients varied from 7.0 months [95% CI, 6.1; 7.8] in the KBPCarb-Esubgroups to 9.6 months [95% CI, 8.4;10.8] in the KBP Cisp-E subgroup. KBP-PS_0/1 population showed better median OS, especially for the Cisp-E subgroup (10 months [95% CI, 8.7; 11.3]). CONCLUSION: In the KBP-PS_0/1 population, median OS was close to the one that was found in the IMpower133 control arm. Although this needs to be confirmed by further research, it suggests the transposability of the IMpower133 results to real-life conditions.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/epidemiologiaRESUMO
INTRODUCTION: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. METHODS: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score. RESULTS: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95% CI: 2.3-10.8) versus 9.1% (95%CI: 6.1-13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55-0.65). CONCLUSION: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.
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Neoplasias/complicações , Medição de Risco/normas , Tromboembolia Venosa/diagnóstico , Adulto , Idoso , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Tinzaparina/farmacologia , Tinzaparina/uso terapêutico , Tromboembolia Venosa/epidemiologiaRESUMO
Background: Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort. Methods: KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010. Findings: In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (p<0·0001). The proportion of non-smokers was higher in 2020 (12·6%, 1129/8983) than in previous cohorts (10·9% (762/7008) in 2010; 7·2% (402/5586) in 2000, p<0·0001). In 2020, at diagnosis, 57·6% (4405/7648) of patients had a metastatic/disseminated stage non-small-cell lung cancer (NSCLC) (58·3% (3522/6046) in 2010; 42·6% (1879/4411) in 2000, p<0·0001). Compared with 2000 and 2010 data, early survival improved slightly. In 2020, 3-month mortality of NSCLC varied from 3·0% [2·2 - 3·8] for localized to 9·6% [8·1 - 11·0] for locally advanced to 29·2% [27·8 - 30·6] for metastatic and was 24·8% [22·3 - 27·3] for SCLC. Interpretation: To our knowledge KBP cohorts have been the largest, prospective, real-world cohort studies involving LC patients conducted in worldwide. The trend found in our study shows an increase in LC in women and still a large proportion of patients diagnosed at metastatic or disseminated stage. Funding: The study was promoted by the French College of General Hospital Pulmonologists with financial support of industrials laboratories.
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INTRODUCTION: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. CONCLUSIONS: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.
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COVID-19 , Neoplasias Pulmonares , Neoplasias Torácicas , Proteína C-Reativa , Teste para COVID-19 , Humanos , Neoplasias Pulmonares/diagnóstico , Prognóstico , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2 , Neoplasias Torácicas/diagnósticoRESUMO
Background and objectives: Few data are available about anticoagulation management beyond 6 months in patients with cancer associated thrombosis (CAT). Our objective was to describe anticoagulant treatment modalities up to 12 months. Methods: The management of the anticoagulant treatment beyond 6 months was described in this initially retrospective non-interventional French multicenter study in patients treated with low-molecular-weight heparins (LMWH) still alive at the end of an initial 6-month treatment period. Clinical outcomes, including venous thromboembolism, recurrence, bleeding and deaths have been published previously. Results: Among the 432 patients (mean age 66.5±12.7 years) included in the study, 332 were followed up to 12 months while 96 patients deceased before study end and 4 patients were lost-to-follow-up. At 6 months, anticoagulant therapy was stopped in 74 patients, 56 were switched to vitamin K antagonists (VKA) (16.1% [95%CI, 12.4%-20.4]), 30 to direct oral anticoagulants (DOAC) (8.6% [95%CI, 5.9%-12.1]). LMWHs were maintained in 256 patients (73.6% [95%CI, 68.6-78.1]). During the follow-up, LMWHs were definitively discontinued in 86 patients (33.7%), the main reason being a favorable course of the cancer (16 patients, 18.6%), or the thromboembolic disease (11 patients, 12.8%), whereas concern about bleeding risk was low (2 patients, 2.3%). Conclusion: Anticoagulation beyond 6 months and up to 12 months was in accordance with clinical practice guidelines suggesting that treatment should be continued as long cancer is active or in the absence of bleeding risk. Anticoagulant treatment discontinuation beyond 6 months was influenced by the favorable courses of both malignancy and thromboembolic disease, as well as patient's preference.