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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.

Publisher Copyright: © 2023 The Author(s). Background: Timeliness of care is an important dimension of healthcare quality but it’s unclear whether it improves clinical outcomes in lung cancer (LC) patients. Objectives: This study aims to analyze treatment patterns, time-to-treatment (TTT) and the impact of treatment timeliness (TT) in overall survival (OS) of patients diagnosed with LC in 2009–2014 in a population-based registry from Southern Portugal. Materials and Methods: We estimated median TTT for overall population, treatment type and stage. The impact of treatment and TT on five-year OS was analyzed using the Kaplan-Meier method and Cox regression modelling to determine the hazard ratio (HR) of death associated with treatment and TT. Results: From the 11,308 cases diagnosed, 61.7% received treatment. Treatment rate decreased with increasing stage from 88% in stage I to 66.1% in stage IV. Overall median TTT was 49 days (IQR: 28–88) and 43.3% received TT. Surgery had a longer TTT than radiotherapy and systemic treatment. Patients in earlier stages had lower TT rates and longer TTT compared to more advanced, 24.7% and 80 days in stage I versus 51.3% and 42 days in stage IV (p < 0.0001). OS was 14.9% for total population and 19.6% and 7.1% for patients with and without treatment registered, respectively. TT had no observed impact on OS for stages I/II but a negative effect for stages III/IV. Relative to treated, the adjusted mortality risk was higher in untreated patients (HR = 2.240; 95%CI: 2.293–2.553). Contrary to treatment, TT had a negative impact on survival, with 11.3% in timely vs. 21.5% in untimely treated. Compared to untimely treated, the risk of death in TT patients was 46.6% higher (HR = 1.465; 95%CI: 1.381–1.555). Conclusions: LC survival is highly dependent on early diagnosis and adequate treatment. Time-to-treatment was longer than recommended for all treatment types but particularly for surgery. Overall TT results were paradoxical, as better survival was observed in patients untimely treated. The factors associated with TT were not possible to analyze and its impact on patient outcomes remains unclear. However, it is important to assess quality-of-care to improved LC management. publishersversion published