Postapproval trials versus patient registries: comparability of advanced melanoma patients with brain metastases.

Postapproval trials and patient registries have their pros and cons in the generation of postapproval data. No direct comparison between clinical outcomes of these data sources currently exists for advanced melanoma patients. We aimed to investigate whether a patient registry can complement or even replace postapproval trials. Postapproval single-arm clinical trial data from the Medicines Evaluation Board and real-world data from the Dutch Melanoma Treatment Registry were used. The study population consisted of advanced melanoma patients with brain metastases treated with targeted therapies (BRAF- or BRAF-MEK inhibitors) in the first line. A Cox hazard regression model and a propensity score matching (PSM) model were used to compare the two patient populations. Compared to patients treated in postapproval trials (n = 467), real-world patients (n = 602) had significantly higher age, higher ECOG performance status, more often ≥3 organ involvement and more symptomatic brain metastases. Lactate dehydrogenase levels were similar between both groups. The unadjusted median overall survival (mOS) in postapproval clinical trial patients was 8.7 (95% CI, 8.1-10.4) months compared to 7.2 (95% CI, 6.5-7.7) months (P < 0.01) in real-world patients. With the Cox hazard regression model, survival was adjusted for prognostic factors, which led to a statistically insignificant difference in mOS for trial and real-world patients of 8.7 (95% CI, 7.9-10.4) months compared to 7.3 (95% CI, 6.3-7.9) months, respectively. The PSM model resulted in 310 matched patients with similar survival (P = 0.9). Clinical outcomes of both data sources were similar. Registries could be a complementary data source to postapproval clinical trials to establish information on clinical outcomes in specific subpopulations.

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis.

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival.Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007-2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use.Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007-2011 to 37% in 2012-2016 (p < .001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007-2011: 12-67%, 2012-2016: 20-54%) whereas overall survival increased from 5.6 months to 6.4 months (p < .001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015-2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015-2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy.Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens.