Number needed to treat analysis applied to pembrolizumab plus chemotherapy for first-line treatment of non-squamous non-small cell lung cancer.

AIMS: Considering that healthcare systems' financial resources are limited, we aimed to analyze the number needed to treat (NNT) and cost of preventing an event (COPE) related to drug use from Supplementary Health System (SSS) perspective. METHODS: Data from KEYNOTE-189 (NCT02578680) were considered, comparing pembrolizumab + chemotherapy to chemotherapy alone. A cost-per-responder model was developed considering the 24- and 12-month time horizons for overall survival (OS) and progression-free survival (PFS) endpoints, respectively. Restricted mean survival time (RMST) and restricted mean time-on-treatment (ToT) were determined for NNT and COPE calculation. Costs were reported in American dollars (USD) and reflect those related to drug use. The analysis was conducted for the total indicated population, and an exploratory assessment was carried out for subgroups with different programmed death-ligand 1 (PD-L1) expression levels. RESULTS: Considering PFS data, the overall population NNTRMST to prevent a progression event with pembrolizumab + chemotherapy versus chemotherapy was 2.63 (95%CI: 1.90-4.02) with an estimated COPE of 251,038 USD (95%CI: 181,359-383,717) in the 12-months follow-up. Regarding OS endpoint, overall NNTRMST and COPE were 3.18 (95%CI: 2.20-5.31) and 414,163 (95%CI: 286,528-691,573) USD respectively, in the 24 months follow-up. The PFS NNT was lower with higher levels of PD-L1 expression (1.71, 3.22 and 5.53 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively), while there was no such apparent relationship for OS (3.23, 4.37 and 2.80 for PD-L1 ≥ 50%, PD-L1 1%-49%, and PD-L1 < 1% groups, respectively). The 95%CIs overlapped for PFS and OS NNT across the PD-L1 subgroups. CONCLUSION: The magnitude of benefit of the pembrolizumab combination used for first-line non-small cell lung cancer (NSCLC) treatment to improve survival compared to chemotherapy alone was confirmed. The exploratory analysis from the SSS perspective suggests no differences among the PDL-1 subgroups in terms of clinical benefit or economic impact.

Análise de custo-efetividade do painel de sequenciamento de nova geração do DNA circulante tumoral no diagnóstico dos pacientes com câncer de pulmão de não pequenas células não escamoso metastático / Cost-effectiveness analysis of next generation sequencing panel of circulating tumor DNA in the diagnosis of patient with metastatic non-squamous non- small cell lung cancer

Objetivo: Avaliar o impacto clínico e econômico do uso do perfil genômico utilizando Next Generation Sequencing (NGS) em DNA circulante tumoral (ctDNA) na escolha do tratamento de primeira linha (1L) dos pacientes com câncer de pulmão de células não pequenas, não escamoso, metastático e que não apresentam material tecidual suficiente para avaliação das mutações oncogênicas. Métodos: Foi realizada uma análise de custo-efetividade com base em um modelo de árvore de decisão e um modelo de Markov para simular os resultados dos testes diagnósticos e consequentemente o seu impacto clínico e econômico na primeira linha de tratamento. O comparador da análise foi o teste de mutações específicas no gene EGFR por ctDNA. As terapias medicamentosas incluídas na análise foram as terapias-alvo de EGFR e ALK, que estão incorporadas no rol da Agência Nacional de Saúde Suplementar, e a imunoterapia pembrolizumabe combinada à quimioterapia. Os desfechos clínicos foram retirados dos estudos clínicos das terapias avaliadas no modelo. Resultados: O uso do painel de NGS em ctDNA demonstrou uma economia de -R$ 2.076,35 por paciente em um ano, e os resultados de RCEI foram: -R$ 7.652,56 (R$/SLP) e -R$ 33.742,14 (R$/SG). Conclusão: O painel de NGS em ctDNA demonstrou ser uma alternativa dominante em relação ao teste de EGFR em ctDNA.

Objective: The aim of this study was to evaluate the clinical and economic impact of the next generation sequencing (NGS) panel of circulating tumor DNA (ctDNA) in the clinical decision of first line treatment for patients with metastatic non-squamous non-small cell lung cancer who lack of tissue material for evaluation of oncogenic driver mutations. Methods: A cost-effectiveness analysis was performed based on a decision tree model and a Markov model in order to simulate the results of diagnostic tests and therefore its clinical and economic impact in the first line of treatment. The comparators were the single EGFR mutation detection methodologies in ctDNA. The analysis included the anti-EGFR and anti-ALK target therapies; and the combined therapy of pembrolizumab plus chemotherapy. Clinical outcomes were derived from clinical trials of the therapies included in the model. Results: The use of the NGS ctDNA panel showed a saving of -R$ 2,076.35 and the results of the ICER were -R$ 7,652.56 (R$/SLP) and -R$ 33,742.14 (R$/SG). Conclusion: The NGS panel demonstrated to be a dominant alternative in comparison to ctDNA EGFR testing.

Survival and prognostic factors in patients with Non-Small Cell Lung Cancer treated in private health care / Sobrevida e fatores prognósticos em pacientes com câncer de pulmão de células não pequenas assistidos na saúde suplementar

INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival of patients with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. RESULTS: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages. .

INTRODUÇÃO: Dados de desfechos em câncer de pulmão de células não pequenas (CPCNP) são escassos no contexto da saúde suplementar no Brasil. O objetivo deste estudo foi descrever as características, tratamentos realizados e a sobrevida desses pacientes em uma instituição oncológica privada brasileira. MÉTODOS: Foram revisados os prontuários de pacientes atendidos entre 1998 e 2010 com diagnóstico de CPCNP. Os dados foram transferidos para uma ficha clínica individual e posteriormente analisados. Pacientes ou familiares foram contatados a fim de otimizar o seguimento e a estimativa da sobrevida. RESULTADOS: Foram incluídos 566 pacientes, com idade mediana de 65 anos. Predominaram os diagnósticos em estádios avançados (79,6% III/IV). A sobrevida mediana foi de 19,0 meses (IC95% 16,2 - 21,8), sendo de 99,7, 32,5, 20,2 e de 13,3 meses nos estádios I, II, III e IV, respectivamente (p < 0,0001). Entre os pacientes que receberam quimioterapia paliativa, a sobrevida mediana foi de 12,2 meses (IC95% 10,0 - 14.4). CONCLUSÕES: Os desfechos encontrados se assemelham aos de países desenvolvidos. Apesar do maior acesso médico em pacientes com cobertura de planos de saúde, a maioria dos diagnósticos ocorre tardiamente. .

Survival and prognostic factors in patients with non-small cell lung cancer treated in private health care.

INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival of patients with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. RESULTS: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages.

Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2.

PURPOSE: To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. PATIENTS AND METHODS: In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m(2)) or CP (area under the curve of 5 and 500 mg/m(2), respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS). RESULTS: A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm. CONCLUSION: Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

Survival data in elderly patients with locally advanced non-small cell lung cancer.

Combined chemoradiation (CRT) is the standard therapy in locally advanced non-small cell lung cancer (NSCLC). Nevertheless, the best approach in the elderly population is still poorly defined. We retrospectively reviewed the charts of elderly (≥ 65 years) patients with unresectable, locally advanced NSCLC, diagnosed at the Brazilian National Cancer Institute between 2003 and 2007. The primary outcome was overall survival (OS), measured from diagnosis until death. Palliative therapy (PT) included best supportive care radiation therapy (RT; ≤ 40 Gy) and palliative chemotherapy. Among patients treated with radical RT, OS was measured from date of treatment beginning until death (OST). One hundred seventy-one patients were included, with median age of 71 years (range 65-90). Thirty-nine percent received PT, 32 % exclusive RT (>40 Gy), and 29 % CRT (concomitant or sequential). Patients treated with RT and CRT had better OS (median 13.7 months [95 % CI 10.9-16.4] and 15.5 months [95 % CI 13.0-17.9]) than PT (median 4.1 months [95 % CI 3.6-4.6]; p < 0.0001). In the multivariate analysis, RT (HR 0.28 [95 % CI 0.18-0.42]; p < 0.0001) and CRT (HR 0.17 [95 % CI 0.1-0.27]; p < 0.0001) were independently correlated to better survival in comparison with PT. Among patients receiving radical RT, the addition of chemotherapy was correlated to longer OST (median 13.8 [95 % CI 10.6-17.0] vs. 10.8 months [95 % CI 8.6-13.1]; p = 0.018). This benefit was confirmed in the multivariate analysis (HR 0.59 [95 % CI 0.36-0.97]; p = 0.039). Elderly patients with locally advanced NSCLC derived significant survival benefit from radical RT and CRT, suggesting that age should not be a contraindication for these aggressive therapeutic strategies.

Palliative care in poor-performance status small cell lung cancer patients: is there a mandatory role for chemotherapy?

PURPOSE: Small cell lung cancer (SCLC) is an aggressive malignancy but with a high response rate to chemotherapy. Eastern Cooperative Oncology Group performance status (ECOG PS) has been recognized as one of the main prognostic factors in SCLC. There are few data about risk-benefit ratio of chemotherapy over exclusive best supportive care in ECOG PS 3 and 4 patients. This study was performed to assess the outcome of poor ECOG PS SCLC patients that received chemotherapy in our institution. METHODS: A retrospective review of medical records from patients with ECOG PS 3-4 SCLC, who received systemic chemotherapy, was performed between January 2001 and December 2006 at the Instituto Nacional do Câncer, Rio de Janeiro, Brazil. RESULTS: A total of 40 patients were included. Extensive disease was observed in 85% of patients and 25% had PS 4. The median overall survival was 53 days (64 days for ECOG PS 3 and 7 days for ECOG PS 4). There were 30% of early deaths. On univariate analysis, lactate dehydrogenase value, need for hospital admission, and exposure to radiotherapy had impact on survival. ECOG PS 3 patients had better survival than PS 4 patients, even when adjusted for stage. On multivariate analysis, ECOG PS, combined with stage, sustained a major influence on survival. CONCLUSIONS: Median survival for ECOG PS 4 patients treated with chemotherapy in our series was extremely short with a high rate of early deaths. ECOG PS 3 patients also showed a poor survival. These data suggest that we need a more comprehensive approach and further studies, regarding the palliative care of this high-risk population.

Validation of the Portuguese version of functional assessment of cancer therapy-fatigue (FACT-F) in Brazilian cancer patients.

GOALS OF WORK: The purpose of this study was to validate the Portuguese version of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) in order to establish its assessment properties, including validity and reliability in a sample of Brazilian cancer patients. MATERIALS AND METHODS: Two hundred seventy patients with different types of cancer were included for this study; the mean age was 50.5 years. The reliability was assessed by internal consistency and reproducibility. Construct validity was assessed through convergent validity and discriminant validity. Convergent validity was examined by comparing the FACT-F to the SF-36. Discriminant validity of the FACT-F evaluated the ability of the scale to differentiate defined groups, discriminating patients according to Eastern Cooperative Oncology Group Performance Status and different stages of disease. MAIN RESULTS: FACT-F had high internal consistency (Cronbach alpha coefficient was 0.78 for physical well-being, 0.68 for social/family well-being, 0.75 for emotional well-being, 0.74 for functional well-being, 0.91 for fatigue, and 0.92 for total FACT-F). The range of test-retest intraclass correlation was from 0.72 to 0.91 (p < 0.0001). The Pearson product correlation revealed good correlations between the total FACT-F and subscales of the SF-36 in most dimensions, ranging from r = 0.51 to r = 0.76, except for SF-36 physical (r = 0.31). The positive correlations between the SF-36 vitality scale and FACT-F total (r = 0.76) and the fatigue subscale (r = 0.77) support the convergent validity. CONCLUSIONS: The Portuguese version of FACT-F is a reliable and valid instrument to assess quality of life and fatigue, representing a valid tool to screen cancer-related fatigue in Brazilian cancer patients.

Reproducibility of functional assessment of Cancer therapy-fatigue (FACT-F) questionnaire for cancer patients

Objective: The objective of this study was evaluating the reproducibility in Portuguese of Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire for cancer patients by applying it according to the test-retest method. Material and Methods: Subjects were 85 cancer patients with an average age of 51.0 years, being 56 (65.9%) women and 29 (34.1%) men. FACT-F questionnaire consists of 40 items, divided in five domains, and is applied for evaluating quality of life and fatigue in patients with cancer. We used as a measuring tool intraclass correlation coefficient values obtained from two measures of test-retest and scatter plot proposed by Bland-Altman. Results: In 36.5% of cases the questionnaire was self-administered, and in 63.5% of the cases read by an interviewer and filled after verbal answer. Intraclass correlation coefficient values found for the domains were: physical well-being 0.72; social/family well-being 0.91; emotional well-being 0.90; functional well-being 0.86; fatigue subscale 0.88, and for the FACT-F 0.91. The Bland-Altman plot showed to be adequate, since most points were within the limits of reliability. Conclusions: FACT-F questionnaire in Portuguese has good test-retest reproducibility in patients with different types of cancer, performance status and stages.

Osteoartropatia hipertrófica secundária ao carcinoma broncogênico (síndrome de Pierre-Marie-Bamberger) / Hyperthrophic osteoarthropathy associated with bronchogenic carcinoma (Pierre-Marie-Bamberger syndrome)

Descreveremos um raro e memorável caso de osteoartropatia hipertrófica (OAH), cujos sinais e sintomas osteoarticulares da síndrome conduzem ao diagnóstico de adenocarcinoma de pulmão em uma paciente assintomática respiratória. Discutiremos também as diversas particularidades da síndrome, fazendo uma revisão da literatura. Nesta revisão, destacaremos alguns dos novos aspectos de sua obscura etiopatogenia, seu diagnóstico diferencial com doenças reumáticas clássicas e os achados singulares da ressonância magnética, que podem, inclusive, preceder os do RX convencional.