RESUMEN
BACKGROUND: A standard of care for pretreated, advanced non-small-cell lung cancers (NSCLCs), nivolumab has demonstrated long-term benefit when administered for 2 years. We aimed to better discern an optimized administration duration by retrospectively analyzing real-life long-term efficacy in a prospective cohort. METHODS: All nivolumab-treated adults with advanced NSCLCs (01/09/2015 to 30/09/2016) from nine French centers were eligible. On 31/12/2018, patients who are alive ≥ 2 years after starting nivolumab were defined as long-term survivors (LTSs) and were divided into three nivolumab treatment groups: <2, 2, or > 2 years. Co-primary endpoints were LTSs' progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up was 32 months (95% CI, 31.0 to 34.0). The 3-year OS rate for the 259 cohort patients was 16.6%. Among them, 65 were LTSs: 47 treated < 2 years, 7 for 2 years, and 11 > 2 years. Their respective characteristics were: median age: 59, 52, and 58 years; smoking history: 92.9, 100, and 100%; adenocarcinomas: 66, 57.1, and 54.5%. LTSs' median (m)PFS was 28.4 months; mOS was not reached. LTSs' objective response rate was 61.6%. mOS was 32.7 months for those treated < 2 years and not reached for the others. The > 2-year group's 3-year OS was longer. Twenty-eight LTSs experienced no disease progression; 7 had durable complete responses. However, LTSs had more frequent and more severe adverse events. CONCLUSION: In real-life, prolonged nivolumab use provided long-term benefit with 16.6% 3-year OS and 25% LTSs. Survival tended to be prolonged with nivolumab continued beyond 2 years. Prospective randomized trials with adequate design are needed.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Supervivientes de Cáncer , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Francia , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions. METHOD: This was a French retrospective multicenter longitudinal study of 108 consecutive patients with advanced NSCLC, a PD-L1 TPS ≥50% and without EGFR/ALK aberrations who were treated by pembrolizumab, in first line. Patient data were obtained from medical files. RESULTS: The main characteristics of the cohort were: median age [range] 66.7 [37-87] years, 64.8% male, 23.1% with a performance status (PS) of 2, and 88.9% current or former smokers. Eighty-seven percent had stage IV NSCLC at diagnosis, 9.2% untreated brain metastases at inclusion,. With a median follow-up of 8.2 months, the median PFS was 10.1 months (95% CI, 8.8-11.4). The objective response rate was 57.3% (complete response 2.7%, partial response 54.6%). Disease control rate was 71.1%. At 6 months, the OS rate estimated was 86.2%. Treatment-related adverse events (AE) of grade 3 occurred in 8% of patients. There were no grade 4 or 5 AEs. CONCLUSION: In a real-life cohort of advanced NSCLC patients (including PS 2 and untreated brain metastases), with PD-L1 TPS ≥50%, pembrolizumab demonstrates similar PFS to the pivotal clinical trial.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Increased postoperative mortality in low volume centers has contributed to merge and space thoracic surgical centers. Some studies have showed that the likelihood of receiving surgery was lower in lung cancer patients living far from a thoracic surgery center. Our objective was thus to determine whether surgery and survival rates in patients with non-small-cell lung cancer (NSCLC) were influenced by the distance between the respiratory and thoracic surgery departments. METHODS: KBP-2010-CPHG is a prospective multicenter epidemiological study including 6083 patients followed in 104 nonacademic hospitals for primary NSCLC diagnosed in 2010. Distance between respiratory and thoracic surgery departments were obtained retrospectively. Predictive factors for surgery and mortality were identified by logistic regression and Cox hazard model. RESULTS: Twenty-three percent of hospitals had a thoracic surgery department; otherwise, mean distance between the hospital and the surgery center was 65km. Nineteen percent of patients underwent surgery. Distance was neither an independent factor for surgery (odds-ratios [95% CI]: 0.971 [0.74-1.274], 0.883 [0.662-1.178], and 1.015 [0.783-1.317] for 1-34, 35-79, and ≥80km vs. 0km) nor for mortality (hazard-ratios [95% CI]: 1.020 [0.935-1.111], 1.003 [0.915-1.099], and 1.006 [0.927-1.091]) (P>0.05). DISCUSSION: This result supports the French national strategy which merges surgery departments and should reassure patients (and physicians) who could be afraid to be lately addressed to surgery or loose chance when being followed far from the thoracic surgical center.