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1.
Ann Hematol ; 102(8): 2137-2151, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301786

RESUMO

Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). The REMIX study is one of the largest prospective, real-world analysis of the effectiveness of IXA-Rd in the setting of RRMM. Conducted in France between August 2017 and October 2019, the REMIX study, a non-interventional prospective study, included 376 patients receiving IXA-Rd in second line or later and followed for at least 24 months. Primary endpoint was the median progression-free survival (mPFS). Median age was 71 years (Q1-Q3 65.0 - 77.5) with 18.4% of participants older than 80 years. IXA-Rd was initiated in L2, L3 and L4 + for 60.4%, 18.1% and 21.5%, respectively. mPFS was 19.1 months (95% CI [15.9, 21.5]) and overall response rate (ORR) was 73.1%. mPFS was 21.5, 21.9 and 5.8 months in patients receiving IXA-Rd as L2, L3, L4 + respectively. Among patients receiving IXA-Rd in L2 and L3, mPFS was similar for patients previously exposed to lenalidomide (19.5 months) than for those lenalidomide naive (not exposed, 22.6 months, p = 0.29). mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older (p = 0.06) with similar ORR (72.4% and 76.8%) in both subgroups. Adverse events (AEs) were reported in 78.2% of patients including 40.7% of treatment-related AE. IXA discontinuation was due to toxicity in 21% of patients. To conclude, the results of the REMIX study are consistent with the results of Tourmaline-MM1 and confirm the benefit of IXA-Rd combination in real life. It shows the interest of IXA-Rd in an older and frailer population, with an acceptable effectiveness and tolerance.


Assuntos
Mieloma Múltiplo , Humanos , Idoso , Lenalidomida/efeitos adversos , Estudos Prospectivos , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
Ann Oncol ; 27(3): 417-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26646759

RESUMO

BACKGROUND: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. PATIENTS AND METHODS: Patients with relapsed/refractory disease following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m(2)/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. RESULTS: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n = 134) or single-agent chemotherapy (n = 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P = 0.003) and ORR (32.1% versus 13.2%, P = 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. CONCLUSION: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. TRIAL REGISTRATION NUMBER: NCT01085136 (clinicaltrials.gov).


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Quinazolinas/uso terapêutico , Afatinib , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/efeitos adversos
4.
BMC Cancer ; 15: 857, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26546402

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. METHODS: Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. RESULTS: Four hundred and six patients were included in 37 sites: mean age 68.9 ± 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioïd type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. CONCLUSIONS: The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Idoso , Gerenciamento Clínico , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Mesotelioma/epidemiologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pleurais/epidemiologia , Estudos Retrospectivos , Fatores de Risco
5.
Ann Oncol ; 25(5): 1044-52, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24585722

RESUMO

BACKGROUND: The randomized, phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer (nsNSCLC). Progression-free survival (PFS) was significantly prolonged with bevacizumab-pemetrexed, but overall survival (OS) data were immature. In this article, we report an independent, updated analysis of survival outcomes in AVAPERL. PATIENTS AND METHODS: Patients with advanced nsNSCLC received first-line bevacizumab (7.5 mg/kg), cisplatin (75 mg/m(2)), and pemetrexed (500 mg/m(2)) every 3 weeks (q3w) for four cycles. Nonprogressing patients were randomized to maintenance bevacizumab (7.5 mg/kg) or bevacizumab-pemetrexed (500 mg/m(2)) q3w until progression or consent withdrawal. The primary end point of the trial was PFS; in this independent OS analysis, participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis. RESULTS: A total of 376 patients received induction treatment. Disease control was confirmed in 71.9% of patients; 253 patients were randomized to maintenance treatment with bevacizumab (n = 125) or bevacizumab-pemetrexed (n = 128). At a median follow-up of 14.8 months, patients allocated to bevacizumab-pemetrexed had significantly improved PFS versus those on bevacizumab when measured from randomization [7.4 versus 3.7 months, hazard ratio (HR), 0.57, 95% confidence interval (CI) 0.44-0.75); P < 0.0001]. OS events occurred in 58% of all patients. OS was numerically longer with bevacizumab-pemetrexed versus bevacizumab when measured from randomization [17.1 versus 13.2 months, HR 0.87 (0.63-1.21); P = 0.29]. Second-line therapy was administered in 77% and 70% of patients in the bevacizumab and bevacizumab-pemetrexed arms, respectively. No new adverse events were reported during this updated analysis. CONCLUSION: In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy, maintenance with bevacizumab-pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Pemetrexede , Modelos de Riscos Proporcionais , Qualidade de Vida , Resultado do Tratamento
6.
ESMO Open ; 9(2): 102220, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232612

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled. RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Renais , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Imunoterapia
7.
ESMO Open ; 9(6): 103473, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833966

RESUMO

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Masculino , Feminino , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , França/epidemiologia
8.
ESMO Open ; 9(6): 103464, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833971

RESUMO

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.


Assuntos
Anticorpos Monoclonais , Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Masculino , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Quimiorradioterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Adulto , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais
9.
Ann Oncol ; 24(6): 1548-52, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23406729

RESUMO

BACKGROUND: The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives. PATIENTS AND METHODS: Prospective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days. RESULTS: Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients. CONCLUSIONS: The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Sci Rep ; 13(1): 11654, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468500

RESUMO

Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4+ T cells (IFNγ, TNFα and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Coqueluche , Humanos , Vacina contra Coqueluche , Coqueluche/prevenção & controle , Estudos Longitudinais , Estudos Prospectivos , Imunização Secundária/métodos , Anticorpos Antibacterianos , Vacinação/métodos , Imunidade
11.
Lung Cancer ; 182: 107280, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37339550

RESUMO

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.


Assuntos
Neoplasias Pulmonares , Segunda Neoplasia Primária , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Pontuação de Propensão , Pulmão
12.
ESMO Open ; 8(5): 101831, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37832389

RESUMO

BACKGROUND: In older patients, comorbidities competed with cancer for mortality risk. We assessed the prognostic value of comorbidities in older patients with cancer. PATIENTS AND METHODS: We analysed all patients >70 years of age with colorectal, breast, prostate, or lung cancer included in the prospective ELCAPA cohort. The Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score was used to assess comorbidities. The primary endpoint was overall survival (OS) at 3, 12, and 36 months. The adjusted difference in the restricted mean survival time (RMST) was used to assess the strength of the relationship between comorbidities and survival. RESULTS: Of the 1551 patients included (median age 82 years; interquartile range 78-86 years), 502 (32%), 575 (38%), 283 (18%), and 191 (12%) had colorectal, breast, prostate, and lung cancer, respectively, and 50% had metastatic disease. Hypertension, kidney failure, and cognitive impairment were the most common comorbidities (67%, 38%, and 29% of the patients, respectively). A CIRS-G score >17, two or more severe comorbidities, more than seven comorbidities, heart failure, and cognitive impairment were independently associated with shorter OS. The greatest effect size was observed for CIRS-G >17 (versus CIRS-G <11): at 36 months, the adjusted differences in the RMST (95% confidence interval) were -6.0 months (-9.3 to -2.6 months) for colorectal cancer, -9.1 months (-13.2 to -4.9 months) for breast cancer, -8.3 months (-12.8 to -3.9 months) for prostate cancer, and -5.5 months (-9.9 to -1.1 months) for lung cancer (P < 0.05 for all). CONCLUSIONS: Comorbidities' type, number, and severity were independently associated with shorter OS. A 17-point cut-off over 56 for the total CIRS-G score could be considered in clinical practice.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Prognóstico , Estudos Prospectivos , Neoplasias Pulmonares/epidemiologia
13.
Eur Respir J ; 39(1): 172-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21659409

RESUMO

Several clinical and biological parameters are known to influence the efficacy of second-line erlotinib therapy for nonsmall cell lung cancer (NSCLC), but their medico-economic impact has not been evaluated. The objective of this study was to compare the incremental cost-effectiveness ratios of strategies for second-line erlotinib initiation in NSCLC: clinically guided initiation (nonsmoking females with adenocarcinoma received erlotinib; all other patients received docetaxel) and biologically guided selection (patients with epidermal growth factor receptor (EGFR) mutation received erlotinib; patients with wild-type EGFR or unknown status received docetaxel), compared with initiation with no patient selection (strategy reference). A Markov model was constructed. Outcomes (overall and progression-free survival), transition probabilities and direct medical costs (from the French third-party payer's perspective) were prospectively collected for individual patients treated with either erlotinib or docetaxel, from treatment initiation to disease progression. Published data were used to estimate utilities and post-progression costs. Sensitivity analyses were performed. The biologically and clinically guided strategies were both more efficient (incremental quality-adjusted life-yrs equal to 0.080 and 0.081, respectively) and less expensive (cost decrease equal to €5,020 and €5,815, respectively) than the no-selection strategy, and the biologically guided strategy was slightly less expensive than the clinically guided strategy. Sensitivity analyses confirmed the robustness of the results. The cost-effectiveness of second-line NSCLC treatment is improved when patients are selected on either clinical or biological grounds.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Análise Custo-Benefício , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Receptores ErbB/genética , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Cadeias de Markov , Oncologia/economia , Oncologia/métodos , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/economia , Qualidade de Vida , Quinazolinas/economia , Sensibilidade e Especificidade
14.
Br J Cancer ; 105(8): 1123-30, 2011 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-21934690

RESUMO

BACKGROUND: Elderly cancer patients form a heterogeneous population in which therapeutic decision-making is often difficult. The aim of this randomised phase II trial was to evaluate the feasibility and activity of weekly docetaxel/gemcitabine (DG) followed by erlotinib after progression (arm A) vs erlotinib followed by DG after progression (arm B) in fit elderly patients with advanced non small-cell lung cancer (NSCLC). METHODS: Elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a comprehensive geriatric assessment (socioeconomic, cognitive, depression, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), the time to first progression (TTP1) and safety were secondary endpoints. RESULTS: Between July 2006 and November 2008, 22 centres enrolled 100 patients. TTP2 was 7.5 and 5.8 months in arm A and arm B, respectively; TTP1 was 4.7 and 2.7 months; and the median OS time was 9.4 and 7.1 months; the respective 1-year survival rates were 36.2 and 31.4%. There was no major unexpected toxicity. CONCLUSION: These results suggest that weekly DG, followed by erlotinib, is a promising treatment for fit elderly patients with NSCLC; the efficacy of the reverse sequence was insufficient to recommend it for EGFR-non-selected patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Docetaxel , Esquema de Medicação , Cloridrato de Erlotinib , Avaliação Geriátrica , Humanos , Neoplasias Pulmonares/patologia , Quinazolinas/administração & dosagem , Taxoides/administração & dosagem , Gencitabina
15.
Rev Malad Respir Actual ; 12(2): 2S378-2S382, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33312269

RESUMO

The Covid-19 epidemic has placed considerable strain on healthcare systems in all countries. The impacts are multiple for patients treated for cancer.The objective of this manuscript is to summarize the epidemiological data available on patients with lung cancer developing a Covid infection, in particular the risk factors for aggravation and mortality, to describe the different strategies to improve the management of these patients and to summarize the existing recommendations in this area.The largest cohort on this subject, Teravolt, which included 1012 patients, found a hospitalization rate of 72 %, an aggravation rate of 56 % and a mortality of 32 %. In multivariate analysis, age ≥65 years (OR 1.53 CI 1.11-2.1), active smoking (OR 2 CI 1.3-3), metastatic status (OR 1.9 CI 1, 3-2.7), an ECOG PS ≥2 (OR 3.7 CI 2.7-5), taking corticosteroids before COVID infection (OR 1.8 CI 1.2-2.7), are associated with a higher risk of mortality but not treatments with chemotherapy or targeted therapies. Interestingly, treatment with immunotherapy appears to decrease the risk of mortality (OR 0.6 CI 0.97)Several screening strategies for asymptomatic forms have been reported in the literature and seem useful for diagnosing asymptomatic forms in patients undergoing systemic treatment or radiotherapy. Finally, national and international recommendations converge on many points, in particular for the need to protect patients and their families from Covid by assessing the benefit / risk of treatment on a case-by-case basis.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

16.
Rev Mal Respir ; 37(1): 1-7, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31862137

RESUMO

BACKGROUND: Given its morbidity and mortality, lung cancer is a major public health issue. In recent years, it has benefited from several therapeutic innovations. The objective of this study was to compare, over two distinct periods of ten years, the impact on survival and the costs of lung cancer management. METHODS: The monocentric study assessed survival and the direct costs of lung cancer management of patients diagnosed in Brest University hospital in 2004 and in 2014. RESULTS: The analysis included 142 patients in 2004 and 156 in 2014. Most patients were smokers (72%), metastatic at diagnosis (60%) both in 2004 and in 2014. Median survival was not significantly improved between the 2 periods (9.7 versus 10.9 months), but there was a significant increase in the average cost of care per patient (€ 17,063 vs. € 29,264, P=<0.0001) between 2004 and 2014. CONCLUSION: The significant increase in treatment costs did not translate into an improvement in the survival of patients with lung cancer between 2004 and 2014.


Assuntos
Atenção à Saúde , Custos de Cuidados de Saúde/tendências , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/terapia , Adenocarcinoma/economia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção à Saúde/economia , Atenção à Saúde/tendências , Feminino , França/epidemiologia , História do Século XXI , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
17.
Int J Tuberc Lung Dis ; 13(7): 881-7, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19555539

RESUMO

BACKGROUND: France was one of the few European countries without a national tuberculosis (TB) treatment outcome monitoring system until 2007. OBJECTIVE: To examine TB management and treatment outcomes in the eastern Paris region, and to identify patient- and management-dependent factors affecting treatment outcome. METHODS: This retrospective study focused on all cases of microbiologically confirmed Mycobacterium tuberculosis cases diagnosed in 2004 in the eastern Paris region, one of the areas of France with the highest frequency of TB. RESULTS: Treatment outcomes of 629 identified cases (males 69.6%, median age 37 years, socio-economically disadvantaged 44%, foreign-born 78%) were as follows: treatment success 70.1% (95%CI 66.5-73.7), treatment interruption 4.9% (95%CI 3.2-6.6), loss to follow-up 15.0% (95%CI 12.2-17.8), death 5.7% (95%CI 3.9-7.9), transfers 4.3% (95%CI 3.5-5.1). Non-completion of treatment was associated with sputum smear positivity, injection drug use, non-adherence and irregular follow-up in univariate analysis, and with irregular follow-up and non-adherence in multivariate analysis. Duration of TB treatment and follow-up medical visits were not applied as recommended in more than a third of cases. CONCLUSION: The treatment success rate observed in this study (70.1%) is below the World Health Organization target of 85%, and requires the implementation and evaluation of interventions to increase treatment success rates.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adulto , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Logísticos , Masculino , Paris/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos , Resultado do Tratamento
19.
Rev Mal Respir ; 26(7): 769-72, 2009 Sep.
Artigo em Francês | MEDLINE | ID: mdl-19953019

RESUMO

INTRODUCTION: Choriocarcinoma is a rare tumour which results from the anarchic proliferation of a gonadic or extra gonadic germinal cell. CASE REPORT: A 45 year old pre menopausal woman of African origin presented with a persistent cough and deterioration of general status. The chest X-ray revealed a cavitated mass of the right upper lobe. Other lesions were associated (liver, kidney and scalp). Choriocarcinoma, suspected in the presence of an elevated ssHCG without a gravid uterus, was confirmed by biopsy excision of a haemorrhagic cutaneous lesion of the scalp. Despite the poor prognosis methotrexate based chemotherapy resulted in control of the disease and a good remission.


Assuntos
Coriocarcinoma , Neoplasias Pulmonares/secundário , Antimetabólitos Antineoplásicos , Biópsia , Coriocarcinoma/sangue , Coriocarcinoma/diagnóstico , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Coriocarcinoma/secundário , Coriocarcinoma não Gestacional/diagnóstico , Gonadotropina Coriônica/sangue , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/secundário , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Pancreáticas/secundário , Prognóstico , Radiografia Torácica , Indução de Remissão , Couro Cabeludo/patologia , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Tomografia Computadorizada por Raios X
20.
Rev Mal Respir ; 26(7): 759-68, 2009 Sep.
Artigo em Francês | MEDLINE | ID: mdl-19953018

RESUMO

INTRODUCTION: Chronic bronchitis is associated with an increased risk of COPD and health-related quality of life (HRQoL) impairment. The objectives of the study were to estimate the prevalence of chronic bronchitis and to describe its relations with quality of life. METHODS: The French Health Interview Survey was conducted in 2003 in a representative sample of households. Data were collected during an interviewer's visits to the home. Respiratory symptoms and HRQoL (SF-36) were assessed in 9,050 adults aged 45 years and older using a self-administered questionnaire. RESULTS: The prevalence of chronic bronchitis was estimated at 3.5%. Chronic bronchitis was associated with an impaired physical component summary score after adjusting for sex, age and dyspnoea. It was associated with a reduced mental component summary score (MCS) among men. In women, this association was only significant in the absence of dyspnoea. CONCLUSION: The prevalence of chronic bronchitis was 3.5% among adults aged 45 years and older. Chronic bronchitis was associated with impairment in health-related quality of life.


Assuntos
Bronquite Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Fatores Etários , Idoso , Índice de Massa Corporal , Bronquite Crônica/complicações , Interpretação Estatística de Dados , Dispneia/epidemiologia , Feminino , França/epidemiologia , Inquéritos Epidemiológicos , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Abandono do Hábito de Fumar , Inquéritos e Questionários
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