Safety and tolerability of long-term treatment with darolutamide in patients with metastatic castration-resistant prostate cancer

Background In patients with metastatic castration-resistant prostate cancer, darolutamide was well tolerated for 25 months, but minimal long-term safety data are available. Methods Treatment-emergent adverse events (TEAEs) for patients receiving darolutamide for a median of 38 months (n = 13) are described in this pooled analysis of individual patient data from phase 1/2 studies. Results All patients reported TEAEs (mostly grade 1/2). The most common TEAEs were diarrhea, abdominal pain, and nausea. Serious TEAEs were reported in six patients (none related to darolutamide). All treatment-related TEAEs (n = 5) were grade 1. Conclusions Long-term darolutamide treatment was well tolerated; no new safety signals observed

Geriatric Assessment Implementation before Chemotherapy in MEtastatic Prostate Cancer, Results from the Real-Life Study GAMERS

Geriatric assessment (GA) can predict and improve treatment tolerance and estimate overall survival in older patients with cancer. Several international organizations promote GA; however, data related to its implementation in daily clinical practice are still limited. We aimed to describe GA implementation in patients over 75 years old with metastatic prostate cancer treated with docetaxel as first-line treatment, and with positive G8 screening test or frailty criteria. This retrospective real-world study included 224 patients treated from 2014 to 2021 in four French centers, including 131 patients with a theoretical indication of GA. Among the latter, 51 (38.9%) patients had GA. The main barriers to GA were the lack of systematic screening (32/80, 40.0%), unavailability of geriatric physician (20/80, 25.0%), and absence of referral despite a positive screening test (12/80, 15.0%). With GA performed in only one-third of the patients with a theoretical indication in daily clinical practice, mostly due to an absence of screening test, the use of GA is currently sub-optimal

TAXOMET : A French prospective multicentric randomized controlled phase II study comparing docetaxel plus metformin versus docetaxel plus placebo in mCRPC

International audienceBackground: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC.Patients and methods: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL).Results: Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed.Conclusion: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed

EPIGIST: An observational real-life study on patients with metastatic gastrointestinal stromal tumors receiving imatinib.

BACKGROUND:Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology GIST, is an observational multicenter longitudinal follow-up cohort study reporting the prescribing patterns of imatinib in patients with GIST and the impact of the treatment in a real-world (standard clinical) setting. METHODS:Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT-positive GIST and started treatment with imatinib for the first time between May 24, 2002, and June 30, 2010. During routine visits, annual collection of clinical characteristics was requested, i.e., age, GIST stage at diagnosis, history, imatinib treatment duration and dosage, adherence, and concomitant medications. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analyzed using descriptive statistics. RESULTS:Of 151 patients enrolled, imatinib was initiated for 126 patients before enrollment and for 25 patients on the day of enrollment or soon after. The patient characteristics were similar to those in published prospective trials. The estimated 1-, 2-, 3-, and 4-year overall survival rates were 90.4% (95% confidence interval [CI; 84.8%-94.0%]), 84.7% (95% CI [78.1%-89.4%]), 73.0% (95% CI [65.0%-79.4%]), and 60.7% (95% CI [51.4%-68.8%]), respectively. The most common adverse events (AEs) were diarrhea (39%), asthenia (39%), eyelid or periorbital edema (32%), abdominal pain (23%), and anemia (21%). Eight of 126 serious AEs were possibly related to the treatment as assessed by investigators. CONCLUSIONS:Study results showed that patients in real-life populations are generally treated in accordance with national and international clinical recommendations and have outcomes comparable to those of patients in clinical trials