ABSTRACT
BACKGROUND: The majority of patients with newly diagnosed metastatic prostate cancer (PC) initially respond to androgen deprivation therapy (ADT) and are classified as metastatic castration-sensitive PC (mCSPC). Following months to years of ADT, the disease tends to become resistant to ADT. Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC. Following its implementation in routine care, this combined treatment strategy requires more detailed evaluation in a real-world setting. AIM: To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC. METHODS: A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed. This region includes approximately 1.1 million citizens and the oncology departments of Linköping, Jönköping, and Kalmar. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. The primary endpoint was progression-free survival (PFS) at 12 mo, and the secondary endpoints were PFS at 24 mo, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalizations. Exploratory analyses on potential prognostic parameters were performed. RESULTS: Ninety-four patients were eligible and formed the study cohort. PFS at 12 and 24 mo was 75% (95%CI: 66-84) and 58% (46-70), respectively. OS at 12 and 24 mo was 93% (87-99) and 86% (76-96). A total of 91% of patients (n = 86) were given docetaxel according to the standard protocol of 75 mg/m2 every 3 wk (6 cycles), while 9% (n = 8) received a modified protocol of 50 mg/m2 every 2 wk (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate Cox regression analyses show that baseline PSA > 180 vs < 180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors (HR 2.86, 95%CI: 1.39-5.87, P = 0.0041 and 3.36, 95%CI: 1.03-10.96, P = 0.045). Following multivariate analysis, statistical significance remained for PSA (2.51, 95%CI: 1.21-5.19, P = 0.013) but not for metastatic status (2.60, 95%CI: 0.78-8.65, P = 0.12). Febrile neutropenia was recorded in 21% (n = 20) of patients, and 26% (n = 24) had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course. CONCLUSION: Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.
ABSTRACT
In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.
