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Background: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. Methods: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to adverse events (AEs). The Kaplan–Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. Results: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7–35.2) and median duration of treatment was 17.5 months (IQR: 7.8–29.1). Median PFS was 19.5 months (95%CI 14.2–24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2–75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5–50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4–28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4–36.0). TPF was 19.8 months (95%CI 14.2–24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0–29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). Conclusions: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

Funding Information: The authors acknowledge the RON network that cooperated in providing up-to-date information on cases diagnosed and treated with the drug of interest. Participating institutions: Centro Hospitalar Universitário de São João, Centro Hospitalar Universitário Lisboa Norte, Centro Hospitalar Universitário do Algarve, Hospital de Braga, Centro Hospitalar e Universitário de Coimbra, Centro Hospitalar de Trás-os-Montes e Alto Douro, Centro Hospitalar do Funchal, Centro Hospitalar de Vila Nova de Gaia/Espinho, Instituto Português de Oncologia de Coimbra Francisco Gentil, Centro Hospitalar Lisboa Ocidental, Hospital Garcia de Orta, Centro Hospitalar Universitário Lisboa Central, Hospital Distrital de Santarém, Centro Hospitalar de Entre o Douro e Vouga, Hospital da Senhora da Oliveira Guimarães, Centro Hospitalar de Setúbal, Centro Hospitalar e Universitário do Porto, Centro Hospitalar Tondela Viseu, Instituto Português de Oncologia de Lisboa Francisco Gentil, Hospital do Espírito Santo de Évora, Centro Hospitalar Barreiro Montijo, Hospital Beatriz Ângelo, Hospital do Santo Espírito da Ilha Terceira, Hospital do Divino Espírito Santo de Ponta Delgada, Hospital Pedro Hispano, Hospital Litoral Alentejano, Centro Hospitalar do Médio Ave, Hospital Distrital Caldas da Rainha, Centro Hospitalar Médio Tejo, Hospital Santa Luzia de Elvas, Hospital José Joaquim Fernandes Beja, Centro Hospitalar Universitário da Cova da Beira, Centro Hospitalar do Baixo Vouga, Hospital Professor Doutor Fernando Fonseca, Centro Clínico Champalimaud, Hospitais CUF, Hospitais da Luz, Hospitais dos Lusíadas). Publisher Copyright: © 2023, The Author(s). Background: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. Methods: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to adverse events (AEs). The Kaplan–Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. Results: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7–35.2) and median duration of treatment was 17.5 months (IQR: 7.8–29.1). Median PFS was 19.5 months (95%CI 14.2–24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2–75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5–50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4–28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4–36.0). TPF was 19.8 months (95%CI 14.2–24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0–29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). Conclusions: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable. publishersversion published

Additional file 1: Table S1. Characterization of lines of therapy received prior to exposure to palbociclib and AI. Table S2. Sensitivity analysis for progression-free survival. Table S3. Subgroup analysis for progression-free survival.

Dissertação de Mestrado em Biotecnologia Farmacêutica apresentada à Faculdade de Farmácia A expiração de patentes dos medicamentos biológicos, tem aberto portas para a introdução de novos medicamentos - os biossimilares. Estes, são medicamentos similares aos seus biológicos de referência e, que visam aumentar a acessibilidade dos doentes, oferecendo mais alternativas terapêuticas com a mesma eficácia, segurança e qualidade e, ao mesmo tempo reduzir os custos, atenuando as pressões orçamentais e económicas sobre os sistemas de saúde. Além disso, o potencial económico que pode ser atingido, pode também servir como impulsionador de inovação para outras áreas que sejam importantes na sociedade.Com base em estudos recentes, espera-se que com o aumento da utilização de medicamentos biossimilares no período de 2017-2020, possa haver uma poupança de cerca de 120 milhões de euros para o Serviço Nacional de Saúde (SNS) - uma vez que o acesso à maioria dos medicamentos biossimilares em Portugal é suportado pelo Estado, através da sua utilização em meio hospitalar ou por dispensa exclusiva na farmácia hospitalar - reduzindo a sua despesa consideravelmente.No entanto, a adoção destes medicamentos tem sido lenta e limitada por diversos fatores de natureza regulamentar e, devido à inexistência de um consenso a nível europeu, nas políticas em volta destes medicamentos, nomeadamente, a nível da prescrição, aceitação por parte dos profissionais de saúde, utilização e questões relacionadas com a permutabilidade e substituição, bem como pelos respetivos preços.Atualmente, existe pouca informação acerca dos motivos que influenciam a decisão dos médicos, a prescrever medicamentos biossimilares e, em que situações é que estes se sentem mais confortáveis para o fazer. Assim, o objetivo deste estudo é identificar os principais desafios no acesso ao mercado dos medicamentos biossimilares a nível nacional, através da investigação dos fatores que estão associados à aceitabilidade destes medicamentos, por parte dos médicos prescritores, a partir da aplicação de um questionário. The patent expiration of biological medicines has opened doors for the introduction of new medicines - the biosimilars. These, are similar drugs to their reference biologicals, aimedat increasing patient accessibility, offering more therapeutic alternatives with the same effectiveness, safety, and quality while reducing costs, alleviating budgetary and economicpressures on health systems. Besides, the economic potential that can be achieved, can also serve as a driver for innovation in other areas that are important to society.Based on recent studies, it is expected that with the increased use of biosimilars in theperiod 2017-2020, savings of about 120 million euros could be saved for the Serviço Nacional de Saúde (SNS) - since access, the majority of biosimilar medicines in Portugal is borne by the State, through its use in the hospital or by exclusive dispensation in the hospital pharmacy - reducing its expenditure considerably.However, the adoption of these medicines has been slow and limited, by some regulatory factors and due to the lack of consensus at the European level on biosimilars policies, such as prescription, acceptance by health professionals, use and related issues with exchangeabilityand substitution, as well as their prices.Currently, there is little information about the reasons that influence physicians' decisionto prescribe biosimilar medicines, and in which situations they feel more comfortable to doso. Thus, this study aims to identify the main challenges in access to the market of biosimilars at the national level, through the investigation of the factors that are associated with the acceptability of these medicines, by prescribing physicians, from the application of a questionnaire.