Abstract Background Locoregional lymph node metastasis is an important prognostic factor in patients with bladder cancer. Multimodal treatment, depending on preoperative stage, may improve survival. ...The standard imaging modalities for staging (computed tomography CT or magnetic resonance imaging MRI) have an accuracy range of 70–90% for lymph node staging. A more accurate preoperative diagnostic test could improve survival rates even more. Objective To determine whether the use of 2-deoxy-2 F fluoro-D-glucose (FDG) positron emission tomography (PET) in combination with CT (FDG-PET/CT) can increase the reliability of preoperative lymph node staging in patients with nonmetastatic invasive bladder cancer (T2 or higher, M0) or recurrent high-risk superficial disease (T1G3 with or without Tis, M0). Design, setting, and participants Fifty-one patients underwent a preoperative FDG-PET/CT between April 2004 and December 2007. Independent of the result for lymph node status, all patients underwent a radical cystectomy and an extended lymphadenectomy. The FDG-PET/CT and CT results were compared with the definitive pathologic results. Measurements Among the 51 patients, 13 patients had metastatically involved locoregional lymph nodes, diagnosed on histopathology. In six patients, these nodes demonstrated increased FDG uptake on PET. In seven patients, PET/CT did not diagnose the positive lymph nodes. PET/CT was false positive in one patient. Results and limitations For the diagnosis of node-positive disease, the accuracy, the sensitivity, and the specificity of FDG-PET/CT were 84%, 46%, and 97%, respectively. When analysing the results of CT alone, there was accuracy of 80%, sensitivity of 46%, and specificity of 92%. The use of FDG-PET/CT is hampered by technical limitations. Conclusions We found no advantage for combined FDG-PET/CT over CT alone for lymph node staging of invasive bladder cancer or recurrent high-risk superficial disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to ...assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. Methods This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov , number NCT01302041. Findings 67 men were enrolled into the study. 62 patients (92·5%, 95% CI 86·2–98·8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. Interpretation Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer. Funding Astellas Pharma Inc, Medivation Inc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Abiraterone acetate (AA) is licensed for treating metastatic castration-resistant prostate cancer (mCRPC). Real-world data on oncological outcome after AA are scarce. The current ...study assesses efficacy and safety of AA in mCRPC patients previously treated with docetaxel who started treatment during the Belgian compassionate use program (January 2011–July 2012). Patients and methods Records from 368 patients with mCRPC from 23 different Belgian hospitals who started AA 1000 mg per day with 10 mg prednisone or equivalent were retrospectively reviewed (September 2013–December 2014). Prostate-specific antigen (PSA) response (decrease≥50%), time to PSA progression (increase>50% over PSA nadir in case of PSA response/>25% in absence of PSA response), time to radiographic progression (on bone scans or for soft tissue lesions using Response Evaluation Criteria In Solid Tumors 1.1), overall survival and adverse event rate (Common Terminology Criteria for Adverse Events v4.03) were analyzed. Kaplan-Meier statistics were applied. Results Overall, 92 patients (25%) had an Eastern Cooperative Oncology Group performance status≥2. Median age was 73 years, median PSA was 103 ng/dl. PSA response was observed in 131 patients (37.4%). Median time to PSA and radiographic progression was 4.1 months (95% CI: 3.6–4.6) and 5.8 months (5.3–6.4), respectively. Median overall survival was 15.1 months (13.6–16.6). Most common grade 3 to 4 adverse events were anemia (13.9%), hypokalemia (7.3%), fatigue (6.8%), and pain (6.3%). Median duration of AA treatment was 5.3 months (interquartile range: 2.8–10.3). The main study limitation is its retrospective design. Conclusions These real-world data on post-docetaxel AA efficacy are in line with the COU-AA-301 trial. Importantly, incidence of severe anemia and hypokalemia is up to 50% higher than reported in previous studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some ...cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported.
To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment.
Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required.
Patients received enzalutamide 160mg/d orally.
The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints.
Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1–8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6–5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported.
Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment.
Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment.
In this prospective, single-arm study, enzalutamide showed antitumour activity in some patients with metastatic castration-resistant prostate cancer who had previously progressed following at least 24 wk of treatment with abiraterone acetate. Adverse events were consistent with the established safety profile of enzalutamide.
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Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with ...metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit.
Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point.
In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain.
In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.
A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal ...effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years.
In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline).
No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4–97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1–L4 or forearm (range –2.7% to –0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of –6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain.
Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years.
Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a ...structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment.
Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period.
Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months.
Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment.
ClinicalTrials.gov identifier NCT02200614.
Abstract Background Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide ...monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen PSA response at week 25), regardless of metastases at baseline, and favorable tolerability. Objective To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. Design, setting, and participants Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl). Intervention Oral enzalutamide 160 mg/d until disease progression or unacceptable toxicity. Outcome measurements and analysis PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). Results and limitations The median (range) age was 73 (48–86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92–100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. Conclusions Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. Patient summary In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. Trial registration NCT01302041
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction
Recent research in the field of cancer‐related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and ...fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors.
Methods
Patients (≥18 years) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated with a baseline neuropsychological assessment including Patient‐Reported Outcome Measures (PROMs). PROMs entailed distress, anxiety and depression, fatigue, and cognitive complaints. The neuropsychological assessment comprised several cognitive domains such as premorbid IQ, attention, processing speed, flexibility, verbal and visual episodic memory, and verbal fluency.
Results
Cross‐sectional data of 125 patients were collected. Patients had a mean age of 60.9 years (range: 30.0‐85.0) and comprised primarily females (65.6%). Patients presented with cancer of following sites: breast (44.0%), digestive (28.8%), urological (11.2%), gynecologic (8.0%), hematologic malignancy (4.8%), and lung (3.2%). Patients presented with a premorbid IQ of 105.3 (range: 79.0‐124.0). In 29.6% of patients, a CRCI was detected. Binary logistic regression analyses showed that a lower premorbid IQ (β = −.084, P < .01) and a higher level of fatigue (β = −.054, P < .05) predicted baseline CRCI. Premorbid IQ also predicted performance on individual cognitive domains. Some domains were also influenced by age, gender, having a breast cancer diagnosis, and an active treatment for hypertension.
Conclusion
Premorbid IQ and fatigue are important predictors of baseline CRCI. Therefore, we advise researchers to implement a short IQ test when conducting clinical trials on CRCI.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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