RESUMEN
Importance: Standard of care for unresectable locally advanced non-small cell lung cancer (NSCLC) involves definitive chemoradiotherapy followed by maintenance therapy with durvalumab. However, the cost of durvalumab has been cited as a barrier to its use in various health systems. Objective: To evaluate the cost-effectiveness of durvalumab vs placebo as maintenance therapy in patients with unresectable stage III NSCLC from 4 international payer perspectives (US, Brazil, Singapore, and Spain). Design, Setting, and Participants: In this economic evaluation, a Markov model was designed to compare the lifetime cost-effectiveness of maintenance durvalumab for unresectable stage III NSCLC with that of placebo, using 5-year outcomes data from the PACIFIC randomized placebo-controlled trial. Individual patient data were extracted from the PACIFIC, KEYNOTE-189, ADAURA, ALEX, and REVEL randomized clinical trials to develop a decision-analytic model to determine the cost-effectiveness of durvalumab compared with placebo maintenance therapy over a 10-year time horizon. Direct costs, adverse events, and patient characteristics were based on country-specific payer perspectives and demographic characteristics. The study was conducted from June 1, 2022, through December 27, 2023. Main Outcomes and Measures: Life-years, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated at country-specific willingness-to-pay thresholds ([data reported in US$] US: $150â¯000 per QALY; Brazil: $22â¯251 per QALY; Singapore: $55â¯288 per QALY, and Spain: $107â¯069 per QALY). One-way and probabilistic sensitivity analyses were performed to account for parameters of uncertainty. A cost-threshold analysis was also performed. Results: The US base-case model found that treatment with durvalumab was associated with an increased cost of $114â¯394 and improved effectiveness of 0.50 QALYs compared with placebo, leading to an ICER of $228â¯788 per QALY. Incremental cost-effectiveness ratios, according to base-case models, were $141â¯146 for Brazil, $153â¯461 for Singapore, and $125â¯193 for Spain. Durvalumab price adjustments to the PACIFIC data improved cost-effectiveness in Singapore, with an ICER of $45â¯164. The model was most sensitive to the utility of durvalumab. Conclusions and Relevance: In this cost-effectiveness analysis of durvalumab as maintenance therapy for unresectable stage III NSCLC, the therapy was found to be cost-prohibitive from the perspective of various international payers according to country-specific willingness-to-pay thresholds per QALY. The findings of the study suggest that discounted durvalumab acquisition costs, as possible in Singapore, might improve cost-effectiveness globally.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Análisis Costo-Beneficio , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/economía , Brasil , España , Años de Vida Ajustados por Calidad de Vida , Masculino , Singapur , Femenino , Estados Unidos , Persona de Mediana Edad , Estadificación de Neoplasias , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/economía , Cadenas de Markov , Análisis de Costo-EfectividadRESUMEN
OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Masculino , Femenino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , España , Anticuerpos Monoclonales/uso terapéutico , Adulto , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Estadificación de Neoplasias , Supervivencia sin Progresión , Quimioterapia de Consolidación , Antígeno B7-H1/antagonistas & inhibidoresRESUMEN
PURPOSE: Spanish Lung Cancer Group (SLCG) conducted a review to analyze the barriers to access to innovative targeted therapies for non-small cell lung cancer (NSCLC) in clinical practice in Spain. METHODS: Review all relevant content published on websites of European Commission, European Medicines Agency, and Spanish Agency of Medicines and Medical Products regarding the authorization and access to oncology treatments. RESULTS: More than 20 targeted therapies are available to treat different molecular alterations in patients with NSCLC. European Commission has approved treatments for genomic alterations involving the following genes: ALK, RET, ROS1, EGFR, BRAF, NTRK, KRAS, MET. However, the availability of these therapies in Spain is not complete, as innovative treatments are not reimbursed or funded late, with only five of these alterations currently covered by National Health System. CONCLUSION: SLCG considers imperative to improve the access in Spain to innovative treatments for NSCLC to reduce inequity across European countries.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas Tirosina Quinasas/genética , España , Proteínas Proto-Oncogénicas/genética , MutaciónRESUMEN
Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurrent chemo-radiotherapy is the standard of care for LS-SCLC that is not surgically resectable, followed by prophylactic cranial irradiation (PCI) for patients without progression. For extensive-stage (ES)-SCLC, a combination of platinum and etoposide has historically been a mainstay of treatment. Recently, the efficacy of programmed death-ligand 1 inhibitors combined with chemotherapy has become the new front-line standard of care for ES-SCLC. Emerging knowledge regarding SCLC biology, including genomic characterization and molecular subtyping, and new treatment approaches will potentially lead to advances in SCLC patient care.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Etopósido/uso terapéutico , Platino (Metal)/uso terapéutico , Estudios de Seguimiento , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: Immunotherapy has revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS: Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS: After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3-5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION: At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Moduladores de Tubulina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos Fase III como Asunto , Progresión de la Enfermedad , Docetaxel/efectos adversos , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Inmunoterapia/mortalidad , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Moduladores de Tubulina/efectos adversos , Adulto JovenRESUMEN
OBJECTIVES: Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. MATERIALS AND METHODS: GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250â¯mg daily or gefitinib 250â¯mg daily plus olaparib 200â¯mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. RESULTS: Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3-13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1-14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00-1.92; pâ¯=â¯0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. CONCLUSIONS: The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination's safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Supervivencia sin Enfermedad , Receptores ErbB/genética , Gefitinib/uso terapéutico , Objetivos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , México , Mutación , Ftalazinas , Piperazinas , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , EspañaRESUMEN
INTRODUCTION: The Memorial Pain Assessment Card (MPAC), validated in 1987, is a card utilised for the self-assessment of cancer pain. The MPAC provides a quick, reliable measure of quality of life. MATERIALS AND METHODS: This study is a linguistic adaptation of the original version of the MPAC into the Spanish language and its validation. This was a multicentre, cross-sectional, observational study. Linguistic adaptation was carried out by four independent translators and two medical oncologists. The MPAC includes 4 subscales: three are visual analogue scales (VAS) measuring pain relief (VASPR), pain intensity (VASPI) and mood (VASMOOD). A fourth subscale consists of a set of pain severity descriptors (Tursky scale). RESULTS: VASPR has been validated in a subsequent prospective follow-up study. The validation of the MPAC subscales included: reliability (Cronbach's coefficient), internal validation (Spearman's coefficient) and external validation (McGill Pain Questionnaire, MPQ; Profile of Mood States, POMS; Hamilton Depression Scales, HDRS; and Zung Anxiety Scale, ZAS). A moderately high reliability of the VASPI, Tursky and VASMOOD subscales (alpha=0.72) was observed. Regarding internal validity, VASPI correlated significantly with Tursky and VASMOOD. However, they showed a non-significant correlation between each other. Regarding external validity, VASPI, Tursky and VASMOOD were correlated with most of the MPQ subscales. VASMOOD and Tursky correlated with most of the POMS subscales, but not with HDRS or ZAS. VASPI showed a non-significant correlation with all of the psychological distress measures. CONCLUSIONS: Our findings showed a successful validation of the VASPI, VASMOOD and Tursky subscales of the MPAC Spanish version.
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Dimensión del Dolor/métodos , Adulto , Afecto , Anciano , Analgesia , Ansiedad/diagnóstico , Ansiedad/etiología , Estudios Transversales , Depresión/diagnóstico , Depresión/etiología , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Neoplasias/fisiopatología , Neoplasias/psicología , Dolor/diagnóstico , Dolor/etiología , Dolor/psicología , Manejo del Dolor , Dimensión del Dolor/normas , Dimensión del Dolor/estadística & datos numéricos , España , Estrés Psicológico/diagnóstico , Estrés Psicológico/etiologíaRESUMEN
INTRODUCTION: Pain intensity is a good parameter to assess effective treatment of cancer and palliative care. The Memorial Pain Assessment Card (MPAC) is a quick, easy and reliable measure of quality of life in cancer patients. The MPAC was validated in Spanish in 2004. This study evaluated the sensitivity to change Spanish version of the MPAC. MATERIAL AND METHODS: An epidemiological, prospective, 1- month, multicentre study, conducted at 4 oncology services. Patients evaluated suffered chronic cancer pain and were in a susceptible situation of change. The MPAC was administrated at baseline, at one week and at one month, including the 4 subscales (pain relief [VASPR], pain intensity measured by VAS [VASPI] and by an 8-item descriptor [Tursky], and psychological distress [VASMOOD]). Satisfaction of patients and health-care professionals with the MPAC was also evaluated. RESULTS: A total of 54 patients were studied. All of the MPAC subscales showed sensitivity to change during the follow-up. The subscale values at visit 1 vs. visit 3 were: VASPR 4.5+/-1.9 vs. 6.3+/-2.3, VASPI 6.6+/-1.6 vs. 3.5+/-1.9 and VASMOOD 5.5+/-2.1 vs. 4.0+/-2.1). Patients and healthcare professionals agreed in the facility use MPAC card (63% and 71% of cases, respectively). CONCLUSIONS: The present study showed sensitivity to change among the different MPAC subscales of the Spanish version. Moreover, the MPAC Spanish version has proven to be a good tool accepted by health-care-professionals and patients. Due to its facility of administration, it may allow a useful and quick evaluation of cancer-related pain in the clinical practice.