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BACKGROUND: Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD. METHODS: This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial. RESULTS: Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively). CONCLUSIONS: This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.

Objectives This study describes the initiation of the Dutch Lung Cancer Audit for Lung Oncology (DLCA-L) and reports the first results of three years of clinical auditing. Methods The initiation, dataset, and data quality of the DLCA-L are described. For the analyses, all patients registered from 2017 to 2019 were included. Descriptive statistics were used to assess the first outcomes of the DLCA-L, including results from quality indicators, patient- and tumor characteristics, and the real-world use of immunotherapy. Results The DLCA-L was initiated after the surgery and radiotherapy audit for lung cancer. In total, 33.788 NSCLC patients and 4.293 SCLC patients were registered in the DLCA-L from 2017 to 2019. Seventy-three (97 %) Dutch hospitals participated in the DLCA-L in 2019. The registry became nation-wide in 2020. The data quality improved over the years, with complete cases in 90 % of the NSCLC patients. In total, 15 quality indicators were established based on DLCA-L data to improve processes and clinical outcomes. An example of these quality indicators was brain imaging at diagnosis of stage III NSCLC patients, which increased from 80 % in 2017 to 90 % in 2019 and hospital variation was reduced. The DLCA-L provided data on immunotherapy use in stage IV NSCLC (n = 4.415) patients. These patients had a median age of 67 years and 11 % of the patients had an ECOG PS ≥ 2. The number of patients treated with immunotherapy in different hospitals varied between 2 patients to 163 patients per hospital. Conclusion The DLCA-L has become a valuable and complete data source with national coverage in 2020. A high number of registered patients and limited missing data resulted in better insights into hospital processes and outcomes of lung cancer care. Quality indicators were, with success, used to establish improvements and minimize hospital variation. The DLCA-L also provides hospitals real-world information on the use of (systemic) therapies.

Background This study aimed to provide insights into the real-world use of palbociclib, dose reductions, and drug effectiveness in (older) patients with advanced breast cancer (BC). Patients and methods Patients with advanced BC treated with palbociclib from 2017 to 2020 were included. The Kaplan-Meier method was used to calculate time to next treatment (TTNT) and overall survival (OS) for patients with or without dose reductions. These clinical outcomes were also compared in subgroup analyses for older patients (≥70 years) and younger patients (, Highlights • Palbociclib dose reductions occurred in 33% of the real-world patients. • Dose reductions did not lead to poorer overall survival. • Older patients had more dose reductions, but this did not affect overall survival.

The aim was to provide evidence on systemically treated patients with advanced melanoma not represented in phase III trials to support clinical decision‐making. Analysis were performed on advanced melanoma patients diagnosed between 2014 and 2017 in the Netherlands, treated with immune‐ or targeted therapy, who met ≥1 trial exclusion criteria. These criteria were derived from the KEYNOTE‐006 and CHECKMATE‐067/‐066 phase III trials. Prognostic importance of factors associated with overall survival (OS) was assessed with the Kaplan‐Meier method, Cox models, predicted OS probabilities of prognostic subgroups and a conditional inference survival tree (CIST). A nationwide population‐based registry was used as data source. Of 2536 systemically treated patients with advanced melanoma, 1004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria strongly associated with OS in systemically treated ineligible patients were Eastern Cooperative Oncology Group Performance Score (ECOG PS) ≥2, brain metastases (BM) and lactate dehydrogenase (LDH) of >500 U/L. Patients with ECOG PS of ≥2 with or without symptomatic BM had a predicted mOS of 6.5 and 11.3 months and a 3‐year survival probability of 9.3% and 23.6%, respectively. The CIST showed the strongest prognostic covariate for survival was LDH, followed by ECOG PS. The prognosis of patients with LDH of >500 U/L is poor, but long‐term survival is possible. The prognosis of ineligible patients with advanced melanoma in real‐world was very heterogeneous and highly dependent on LDH value, ECOG PS and symptomatic BM., What's new? By necessity, randomized controlled trials (RCTs) exclude many patients. However, these ineligible patients are often still treated with new systemic therapies on an individual basis. In this study, the authors examined how various subgroups of ineligible patients fared following treatment for advanced melanoma. They found that several criteria were strongly associated with prognosis in these patients, including lactate dehydrogenase (LDH) levels. These results should provide clinicians with a decision tree of prognostic factors to help guide treatment decisions.