Background
Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, ...particularly in the real-world setting and among patients who are under-represented in clinical trials.
Objective
We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases.
Patients and methods
Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes overall survival (OS) and time to progression (TTP) of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, “abiraterone”), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population.
Results
The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgen-deprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population.
Conclusions
This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies.
Trial Registration
ClinicalTrials.gov identifier NCT02236637; registered September 2014.
The FIRE study investigated the real-world effectiveness and safety of ibrutinib in prospectively observed patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle ...cell lymphoma (MCL) in France. Patients were mostly relapsed/refractory with high-risk features. First-line CLL/SLL patients had del17p and/or
TP53
mutations. In this interim analysis, the median follow-up time for patients with CLL/SLL and MCL was 17.7 and 15.1 months, respectively. In the effectiveness populations for CLL/SLL (
n
= 200) and MCL (
n
= 59), the median progression-free survival was not estimable and 12.4 months, respectively; the 12-month overall survival rates were 88.5% and 65.8%, respectively. Treatment-emergent adverse events of interest for patients with CLL/SLL (
n
= 202) and MCL (
n
= 59) included: infections and infestations (53.5% and 32.2%), major bleeding (5.0% and 5.1%), and atrial fibrillation (5.9% and 8.5%); 135 (66.8%) and 20 (33.9%) patients were continuing treatment at the time of data cutoff. Future analyses will report on longer-term follow-up (Trial registration: ClinicalTrials.gov, NCT03425591. Registered 1 February 2018—Retrospectively registered,
https://clinicaltrials.gov/ct2/show/NCT03425591
).
Patient characteristics appear to influence the first-line treatment of metastatic castration-resistant prostate cancer. Patients older and with lower Gleason scores tended to receive abiraterone, ...those younger and with more advanced disease tended to receive docetaxel, and those with fewer metastases and more favourable performance tended to receive enzalutamide. The benefit to patients from these observations remains unknown.
Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC).
To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC.
A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted.
Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone–radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE).
Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively.
Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study.
The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution.
Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.
The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and ...Waldenström’s macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or
TP53
mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (
N
= 221: prospective,
n
= 71; retrospective,
n
= 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.
Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or ...intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.
Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 ...monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0-1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1-20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2-36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9-5.6) and 12.4 months (95% CI: 10.3-NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.
Purpose: To explore the time course of treatment‐emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy.
Methods: Post hoc analyses were performed by using data from a large (264 ...subjects) multicenter, double‐blind, placebo‐controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment‐resistant partial‐onset seizures. The daily incidence and mean duration of the most common (≥5% incidence) AEs were calculated for patients completing the 12‐week study.
Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits.
Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy.
Abstract
Background/Aims
Guselkumab (GUS), a human monoclonal antibody targeting the interleukin-23p19-subunit, has demonstrated efficacy at Week 24 (W24) in the Phase IIIb COSMOS clinical trial of ...patients with active psoriatic arthritis (PsA) and inadequate response or intolerance to one or two tumour necrosis factor inhibitors (TNFis). This post hoc analysis aimed to identify predictors of minimal disease activity (MDA) with GUS at W24 in this population.
Methods
Multiple logistic regression analysis was performed to identify potential predictors of MDA with GUS at W24 in TNFi-refractory patients with PsA; odds ratios, 95% confidence intervals and p-values were calculated. Baseline characteristics assessed as predictors included sex, body mass index (BMI), C-reactive protein (CRP), other medication use and disease duration; clinical features included tender and swollen joint counts (TJC/SJC), affected joint location, dactylitis, enthesitis, spondylitis, Psoriasis Area Severity Index (PASI) score and psoriasis (PsO) localisation (Table). Missing data for MDA at W24 were imputed as non-response; missing baseline values were imputed for two patients.
Results
Patients (n = 187; female, 54.6%; mean disease duration, 8.3 years) had mean TJC 0-68 and SJC 0-66 of 21.0 and 10.3, respectively, mean PASI score of 11.6, and mean BMI of 28.9; 67.9% had enthesitis and 35.8% had dactylitis at baseline. One prior TNFi had been received by 88.2% of patients, with two received by 11.8%. At W24, 17.1% (32/187) of patients achieved MDA. Wrist involvement (p = 0.031) and scalp PsO (p = 0.049) were positive predictors of MDA. Women were significantly less likely to achieve MDA vs. men; other negative predictors included hand small joints or shoulder involvement and hand/foot PsO (all p < 0.05). Age, BMI, CRP, TJC/SJC, HAQ-DI, PASI, spondylitis, enthesitis, dactylitis, other medication and number of prior TNFis were not predictive of MDA (Table).
Conclusion
Baseline characteristics and clinical features may be positively (wrist involvement, scalp PsO) or negatively (female sex, hand small joints or shoulder involvement, hand/foot PsO) associated with achieving MDA with GUS at W24 in a TNFi-refractory population. Though the low patient number limits the generalisability of this analysis, assessment of Week 48 data may further elucidate potential predictors of MDA after longer-term treatment.
Disclosure
W. Tillett: Other; William Tillett has received research grants and consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB. S. Ohrndorf: Other; Sarah Ohrndorf has received fees from AbbVie, BMS, Janssen, Novartis and Pfizer. J. Ramírez: Other; Julio Ramírez has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB. M. Neuhold: Other; Marlies Neuhold is an employee of Janssen and owns stocks in Johnson & Johnson. R. Wapenaar: Other; Robert Wapenaar is an employee of Janssen and owns stocks in Johnson & Johnson. E. Theander: Other; Elke Theander is an employee of Janssen and owns stocks in Johnson & Johnson. C. Contre: Other; Christine Contre is an employee of Janssen and owns stocks in Johnson & Johnson. M. Sharaf: Other; Mohamed Sharaf is an employee of Janssen and owns stocks in Johnson & Johnson. M. Shawi: Other; May Shawi is an employee of Janssen and owns stocks in Johnson & Johnson. M. Vis: Other; Marijn Vis has received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation.
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