Teresa Almodovar

An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

AIM Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC) versus docetaxel, pemetrexed and best supportive care. MATERIALS AND METHODS Cost-minimisation and cost-utility analysis were performed. Time horizon of two years. Portuguese National Health System (NHS) perspective was applied. Survival and time to progression were obtained from three clinical trials. Base-case analysis: 2nd or 3rd line patients with advanced or metastatic NSCLC. Quality Adjusted Life Years (QALYs) were obtained from a UK study. Resource consumption was estimated by a Portuguese panel of experts. Costs were calculated according to official Portuguese databases (updated to 2008). Only direct health costs were applied. Annual discount rate: 5%. Sensitivity analysis included different subpopulations, a three year time horizon and a probabilistic analysis. RESULTS The cost per patient was lower with erlotinib (26,478 euro) than docetaxel (29,262 euro) or pemetrexed (32,762 euro) and higher than best supportive care (16,112 euro). QALYs per patient were higher with erlotinib (0.250) than docetaxel (0.225), pemetrexed (0.241) or best supportive care (0.186). Erlotinib was dominant in the cost-utility analysis, with a lower cost and a higher efficacy than docetaxel and pemetrexed. The sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS The use of erlotinib instead of docetaxel or pemetrexed could contribute to annual savings for the NHS (substitution rates: 5%-65%) ranging from 135,046 euro-1,755,602 euro (docetaxel replacement) and 291,801 euro-3,793,409 euro (pemetrexed replacement), with a gain in terms of QALYs.

Avaliação económica do erlotinib, docetaxel, pemetrexedo e tratamento de suporte no tratamento de segunda ou terceira linhas de doentes com cancro do pulmão de não pequenas células

Resumo Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmao de nao pequenas celulas (CPNPC) avancado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte. Material e metodos: Analises de minimizacao de custos e custo-utilidade. Horizonte temporal: dois anos. Perspectiva do Sistema Nacional de Saude (SNS) portugues. Sobrevivencia e tempo ate progressao obtidos a partir de tres ensaios clinicos. Analise-base inclui doentes com CPNPC avancado ou metastizado em segunda ou terceira linhas. Anos de vida ajustados pela qualidade (ou QALY) obtidos a partir de estudo no Reino Unido. Consumo de recursos estimado por painel de peritos portugueses. Incluiram-se apenas custos directos, obtidos a partir de fontes oficiais (precos actualizados para 2008). Taxa de actualizacao anual: 5%. Analises de sensibilidade: diferentes subpopulacoes, horizonte temporal a tres anos e analise probabilistica. Resultados: O custo total/doente foi menor com erlotinib (26 478€) versus docetaxel (29 262€) ou pemetrexedo (32 762€) e superior versus tratamento de suporte (16 112€). Obtiveram-se QALY/doente mais elevados com erlotinib (0,250) versus docetaxel (0,225), pemetrexedo (0,241) ou tratamento de suporte (0,186). Assim, o erlotinib mostrou-se “dominante” em segunda ou terceira linhas versus docetaxel e pemetrexedo. A analise de sensibilidade comprova a robustez dos resultados. Conclusoes: A substituicao de docetaxel ou pemetrexedo por erlotinib poderia contribuir para uma reducao anual dos gastos do SNS que se estima (taxas substituicao: 5%-65%) com uma variacao entre 135 046€-1 755 602€ e entre 291 801€-3 793 409€, respectivamente, e com ganho em termos de QALY. Rev Port Pneumol 2008; XIV (6): 803-827

Oral vinorelbine plus cisplatin as first-line chemotherapy in nonsquamous non-small-cell lung cancer: final results of an International randomized phase II study (NAVotrial 01).

BACKGROUND The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non-small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC. PATIENTS AND METHODS Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 (arm A) or oral vinorelbine 80 mg/m(2) on days 1 and 8 (first cycle 60 mg/m(2)) and cisplatin 80 mg/m(2) on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine. RESULTS Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm. CONCLUSION Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.

Elderly patients with advanced NSCLC: The value of geriatric evaluation and the feasibility of CGA alternatives in predicting chemotherapy toxicity

Cancer is primarily a disease of the elderly, with the incidence of older patients with cancer expected to increase in the coming years. Despite remarkable advances during the last decade, lung cancer remains a leading cause of mortality worldwide, non-small cell lung cancer (NSCLC) being the dominant (85-90%) subtype. At diagnosis, 50% of NSCLC patients are ≥70 years and 15%, over 80 years of age. Due to their under-representation in clinical trials, current treatment decisions for older patients with cancer are based on a low level of scientific evidence. The little evidence that exists suggests that chemotherapy is effective in elderly NSCLC patients, but also indicates that they are at more risk of chemotherapy toxicity than younger adults. However, if carefully selected and monitored, elderly patients can benefit from standard chemotherapy regimens. The Comprehensive Geriatric Assessment (CGA) has historically been adopted to identify elderly patients who are unfit for chemotherapy, yet in clinical practice this is often not feasible as it is too time-consuming. Two promising new tools have emerged - the CRASH and CARG scores - to assign patients to varying intensities of chemotherapy based on a pre-therapy risk assessment. The strengths and shortcomings of each tool were discussed by a group of six advisors with expertise in the treatment of NSCLC. Based on a literature review and on their personal experience, CRASH and CARG were considered feasible toxicity prediction tools, appropriate for implementation in routine clinical practice, with a potentially high impact in optimizing therapy selection for elderly patients with cancer.

Oral vinorelbine plus cisplatin versus pemetrexed plus cisplatin as first-line treatment of advanced non-squamous non-small-cell lung cancer: cost minimization analysis in 12 European countries.

Abstract Objective: A combination of vinorelbine and cisplatin is a standard treatment in non-small-cell lung cancer; oral vinorelbine is registered in 45 countries. Pemetrexed and cisplatin are recommended in front-line chemotherapy of non-squamous non-small-cell lung cancer (NS-NSCLC). The objective of this study was to conduct a cost minimization analysis from the perspective of the national health service (NHS) in each of 12 European countries, based on a randomized phase II study in NS-NSCLC (NAVoTRIAL01), with 100 oral vinorelbine plus cisplatin patients (arm A) and 51 pemetrexed plus cisplatin patients (arm B). Research design and methods: Country-specific costs and DRG codes considered included those relating to anticancer drugs, administration settings (out-patient/in-patient/at home), serious adverse events (defined as involving hospitalization and considered due to anticancer drugs) and concomitant medications. Relevant costs were calculated based on country-specific reimbursement procedures and official tariffs. Main outcome measures: Cost and savings per patient. Results: Using the NHS perspective, savings per patient treated with oral vinorelbine ranged from €1317 (Denmark) to €35,001 (Germany). Expressed as percentages, savings per patient treated with oral vinorelbine compared with pemetrexed ranged between 5% (France) and 83% (Czech Republic). Pooled average costs for each treatment arm across the 12 countries resulted in cost savings for payers of €12,871, favoring oral vinorelbine plus cisplatin. Conclusions: Given the reported efficacy with both regimens, this pan-European economic analysis provides compelling evidence supporting oral vinorelbine use over pemetrexed for the treatment of NS-NSCLC. Oral vinorelbine provides similar efficacy and an easily manageable safety profile at lower overall cost per patient treated, combined with an easier/more convenient mode of administration. Sensitivity analysis across varied scenarios demonstrated the robustness of the results. The principle weakness of our study was its reliance upon a single small scale study to provide efficacy data, since this is the only study conducted in this specific population of patients. Further large scale trials are needed to confirm these results.

Doentes com neoplasia do pulmão de não pequenas células submetidos a tratamento com erlotinib – Casos clinicos

Resumo Apresentam-se quatro casos clinicos, da nossa expe-riencia do IPO, de doentes com neoplasia do pulmao nao pequenas celulas, tratados em segunda e terceira linhas com erlotinib. Sao doentes seleccionados em que se salienta a boa resposta ao tratamento instituido e a presenca de efeitos secundarios predo-minantemente cutâneos. Rev Port Pneumol 2008; XIV (Supl 3): S65-S69

Tuberculose das Cordas Vocais

Platelet derived serotonin (5HT) contributes to blood pressure elevation and the development of thromboembolic complications. Among the pathophysiological mechanisms involved in these vascular events, derangements in 5HT kinetics and exaggerated platelet response to 5HT may be part of the major triggering factors. An age-dependent attenuation platelet 5HT kinetics was revealed in normotensive control subjects but not in patients with essential hypertension. In older hypertensive patients, particularly in men, platelet 5HT uptake was decreased. In parallel, platelet reactivity was increased with advancing age as shown by a greater 5HT induced platelet aggregation and higher plasma concentration of beta-thromboglobulin. Antihypertensive treatment with the 5HT2-receptor antagonist ketanserin attenuated platelet 5HT turnover and inhibited 5HT induced platelet aggregation; the latter was more pronounced in older patients. The clinical efficacy and tolerability of ketanserin 20-40 mg twice daily given as mono- or combination therapy was evaluated in 188 patients with mild to moderate essential hypertension for a period of 12 weeks. A greater fraction of patients greater than or equal to 60 years achieved diastolic target pressure of less than or equal to 95 mgHg. Complaints related to the central nervous system or the peripheral circulation were greatly reduced in patients older than 60 years. In older patients, over and above the antihypertensive effect, 5HT2-receptor blockade may play an important role in the prevention of thromboembolic complications by inhibition of 5HT induced platelet activation.