30 mei 2018: ASCO 2018
A.s. weekend start ASCO 2018 in Chicago. Hier een selectie van belangrijke abstracten gerelateerd aan prostaatkanker.
Klik op de nummers voor de abstracten zelf. We zullen komende week zeker een aantal abstracten eruit kiezen om die wat uitgebreider te beschrijven maar hier alvast een voorselectie door dr. Brian Lewis die wij hebben overgenomen van ASCO POST:
Session: Genitourinary (Prostate) Cancer
Monday June 4, 3:00 PM–6:00 PM
5001 Accuracy of 68Ga-PSMA11 PET/CT on recurrent prostate cancer: Preliminary results from a phase 2/3 prospective trial. W Fendler, J Calais, J Gartmann, et al
- In this phase II/III study, 250 patients with biochemically recurrent prostate cancer underwent 68Ga-PSMA11 PET/CT. The positive predictive value by histopathology was 85% on a patient base, and the positive predictive value by any determination was 89% on a patient base and 91% on a region base. Recurrent prostate cancer was localized via 68Ga-PSMA11 PET/CT in 79% of patients, which increased with increasing PSA value. A PSA drop of at least 50% was recorded in 78% of patients following focal salvage therapy.
- These results demonstrate the high positive predictive value of 68Ga-PSMA11 PET/CT for localizing recurrent prostate cancer.
5003 Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomized phase II trial. N Clarke, PJ Wiechno, B Alekseev, et al
- In this study, 142 patients with mCRPC were randomized post docetaxel to olaparib 300 mg twice daily or placebo plus abiraterone until disease progression. Radiologic progression-free survival was significantly increased in patients treated with olaparib vs placebo. Patients receiving olaparib reported more frequent adverse events and more frequently discontinued treatment due to an adverse event. Importantly, the time to deterioration in quality of life was not different between treatment groups (5.7 vs 6.0 months).
- The findings show that olaparib plus abiraterone increased survival with some toxicity but at no detriment to quality of life.
Session: Genitourinary (Prostate) Cancer
Saturday June 2, 1:15 PM–4:45 PM
5014 The complete genomic landscape of metastatic prostate cancer pinpoints clinically targetable subgroups. LF van Dessel, J van Riet, M Smits, et al
- Genomic data was gathered from fresh-frozen tissue biopsies of 153 patients with metastatic prostate cancer. In biopsied lesions, the median tumor cell content was 60%. Compared with 0.53 single nucleotide variants (SNVs) per million base pairs (Mbp) in primary disease, there were 2.6 SNVs per Mbp in metastatic tissue. In 8 tumors, high SNV and small insertions and deletions (InDel) load were correlated with microsatellite instability signatures. A median of 59 interchromosomal rearrangements were reported in metastatic tissue compared with 19 in primary disease. Alterations in TP53 and AR were also reported.
- These results highlight the evolution of aberrations in metastatic disease compared with primary disease.
5015 Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI+P) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCPRC): Results for 2nd-line therapy. D Khalaf, M Annala, DL Finch, et al
- In this study, 202 patients with mCRPC received abiraterone plus prednisone (ABI+P) followed by enzalutamide (ENZ) at PSA progression (arm A) or ENZ followed by ABI+P (arm B). A total of 65 patients from arm A and 71 patients from arm B crossed over to second-line treatment. A total of 15 patients from each arm stopped treatment without crossover. Significantly more patients in arm A had an ECOG performance status of 0–1 and LDH above the upper limit of normal compared with patients in arm B. Patients in arm A had a significantly longer median time to PSA progression on second-line therapy and significantly more patients had PSA50. Factors associated with time to PSA progression on second-line therapy included bone metastases, liver metastases, and treatment arm.
- These results demonstrate superior PSA50 and median time to PSA progression on second-line therapy in patients receiving ABI+P followed by ENZ.
5020 Microsatellite instability in prostate cancer and response to immune checkpoint blockade. W Abida, ML Cheng, J Armenia, et al
- In this study, tumors and matched normal tissue from 839 patients with prostate cancer were sequenced and evaluated for microsatellite instability. Of these patients, 2.4% had MSI-H/dMMR tumors, which were confirmed by mutational signature analysis and IHC. Germline MMR gene mutations were found in 3 of 13 MSI-H patients who consented to germline analysis. Of 5 patients who underwent profiling of at least two matched tumors, 3 patients had MSI in the later tumor. Of 10 patients with MSI-H tumors who received PD-1/PD-L1 therapy, 2 had a radiographic partial response and PSA decline of >80%, 3 exhibited a PSA decline of >60%, 1 had stable disease for 6 months then progressed, 3 did not respond, and 1 patient was not evaluable.
- The researchers suggest that germline profiling be recommended in patients with MSI-H prostate cancer. Further studies are warranted to validate the response rates in patients with MSI-H/dMMR prostate cancer who receive PD-1/PD-L1 therapy.
5022 Radium-223 re-treatment in an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases: 2-year follow-up. AO Sartor, D Heinrich, N Mariados, MJ Méndez, et al
- In this international, open-label, phase I/II study, 44 patients with CRPC and bone metastases were retreated with Ra-223, with 66% of patients completing all six Ra-223 injections. Of these patients, 77% entered active follow-up. No new safety concerns and no serious drug-related adverse events were reported. Radiographic progression or death was reported in 59% of patients. Radiographic bone progression was reported in 11% of patients. Median overall survival, time to first symptomatic skeletal event, and symptomatic skeletal event–free survival was 24.4 months, 16.7 months, and 12.8 months, respectively.
- These results demonstrate the tolerability and continuous bone disease control in patients with CRPC and bone metastases who were retreated with Ra-223.
5023 Longer term preplanned efficacy and safety analysis of abiraterone acetate + prednisone (AA + P) in patients (pts) with newly diagnosed high-risk metastatic castration-naïve prostate cancer (NDx-HR mCNPC) from the phase 3 LATITUDE trial. K Fizazi, S Feyerabend, N Matsubara, et al
- In this study, 1199 patients with newly diagnosed high-risk metastatic castration-naïve prostate cancer were randomized to receive abiraterone acetate plus prednisone (AA + P) with ADT or placebo with ADT. At a median of 41 months of follow-up, 34% of patients receiving AA + P plus ADT and 12% of patients receiving placebo plus ADT remained on treatment. Patients receiving AA + P plus ADT exhibited significantly longer overall survival and median time to pain progression, skeletal-related events, chemotherapy initiation, and subsequent prostate cancer therapy. Frequently reported grade 3/4 adverse events included hypertension, hepatotoxicity, hypokalemia, fluid retention, and cardiac disorders. Life-prolonging therapies were given to 54% of patients receiving placebo plus ADT.
- These results further demonstrate the survival benefit of AA + P with ADT in patients with newly diagnosed high-risk metastatic castration-naïve prostate cancer.
5040 Lutetium-177 PSMA617 theranostics in metastatic castrate-resistant prostate cancer (mCRPC): Interim results of a phase II trial. SK Sandhu, JA Violet, J Ferdinandus, et al
- In this phase II study, 50 patients with PSMA-avid mCRPC who progressed on conventional therapy were given up to four cycles of LuPSMA every 6 weeks. At data cutoff, PSA50 was achieved in 62% of patients, including 44% who had a PSA decline of at least 80%. Frequently reported adverse events possibly related to LuPSMA included thrombocytopenia, anemia, and neutropenia. Median PSA progression–free and overall survival were 7 and 12 months, respectively.
- These results demonstrate the safety and promising activity of LuPSMA in men with mCRPC who progressed on conventional therapy.
5046 Patterns of PSA versus clinically progressive disease in the E3805 CHAARTED trial. AH Bryce, Y-H Chen, G Liu, et al
- In this study, 790 men with metastatic prostate cancer were randomized to ADT or ADT plus docetaxel and stratified into high-volume or low-volume disease groups. At data cutoff, 403 men with high-volume disease and 157 men with low-volume disease had progressed. In both arms, men with high-volume disease most commonly experienced PSA disease progression followed by clinical disease progression. Patients with low-volume disease most commonly experienced clinical disease progression without PSA disease progression, which occurred in 44.8% receiving ADT plus docetaxel and 34.4% receiving ADT.
- These results demonstrate the frequency of clinical disease progression without a rise in PSA, highlighting the need to incorporate imaging into treatment monitoring in this patient population.
5051 Efficacy and tolerability of first-line abiraterone + prednisone (ABI) versus enzalutamide (ENZ) for metastatic castration-resistant prostate cancer (mCRPC) in men ≥ 80 years: A retrospective cohort study. D Khalaf, K Zou, WJ Struss, et al
- In this retrospective study, data from 210 patients with mCRPC who were at least 80 years old and received abiraterone plus prednisone (ABI; 106 patients) or enzalutamide (ENZ; 104 patients) for first-line treatment were reviewed to assess outcomes. Time from start of ADT to castration resistance was less than 1 year in significantly more patients receiving ENZ compared with patients receiving ABI (29% vs 16%). Significantly more patients receiving ENZ achieved PSA50 and experienced a significantly longer median time to first progression compared with patients receiving ABI. Significantly more patients receiving ENZ required at least one dose reduction due to toxicity. Patients receiving ENZ who required a dose reduction had longer time to first progression compared with those without a dose reduction.
- These results demonstrate superior outcomes in patients receiving ENZ compared with patients receiving ABI, although there were more dose reductions required in patients receiving ENZ.
5058 Six-month patient-reported outcome (PRO) results from AQUARiUS, a prospective, observational, multicenter phase 4 study in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate + prednisone (AAP) or enzalutamide (ENZ). AT Vuillemin, MH Poulsen, L-M Dourthe, et al
- In this report of 6-month results from the AQUARiUS study, data from 211 chemotherapy-naïve patients with mCRPC who initiated abiraterone acetate plus prednisone (AAP; 105 patients) or enzalutamide (ENZ; 106 patients) were analyzed. Significantly fewer patients receiving AAP exhibited clinically meaningful worsening in cognition and fatigue during the first 6 months of treatment compared with patients receiving ENZ. Furthermore, patients receiving AAP exhibited consistently improved changes from baseline in perceived cognitive impairments, comments from others, fatigue right now, usual level of fatigue, and worst level of fatigue.
- Outcomes related to cognition and fatigue were more favorable in patients with mCRPC who initiated AAP compared with patients who initiated ENZ.
5066 Prostate cancer (PCa) incidence and severity in hypogonadal men treated with testosterone compared to untreated controls: Experience from 6,500 patient-years from a controlled registry study. A Haider, KS Haider
- In this study, 412 symptomatic men received testosterone undecanoate, and 393 hypogonadal men decided against testosterone and were used as the control group; patients were followed to assess the effects of testosterone on prostate cancer development. A total of 2.7% of men receiving testosterone and 8.9% of men in the control group were diagnosed with prostate cancer. Biochemical recurrence was reported in 28.6% of men in the control group, and 34.3% of patients died. No biochemical recurrences or deaths were reported during observation in the group receiving testosterone.
- These results demonstrate that prostate cancer incidence and severity was decreased in hypogonadal men treated with testosterone compared with untreated men.
5079 Ten year treatment outcomes of radical prostatectomy vs external beam radiation therapy vs brachytherapy for 1,503 patients with intermediate risk prostate cancer. BW Goy, RJ Burchette, MS Soper, et al
- In this retrospective study, data from 1503 patients with intermediate-risk prostate cancer were evaluated to assess 10-year treatment outcomes of radical prostatectomy (RP; n = 819), external beam radiation therapy (EBRT; n = 574), and brachytherapy (BT; n = 110). Gleason scores of 7 were reported in 76.3% of patients receiving RP, 72.8% of patients receiving EBRT, and 57.3% of patients receiving BT. Neoadjuvant ADT was given to 0.06% of patients receiving RP, 58.89% of patients receiving EBRT, and 12.7% of patients receiving BT. The 10-year freedom from biochemical failure was 58.0% in patients receiving RP, 58.8% in patients receiving EBRT, and 82.0% in patients receiving BT. The 10-year freedom from salvage therapy was 64.0% in patients receiving RP, 73.4% in patients receiving EBRT, and 89.5% in patients receiving BT. In multivariable analysis, BT remained an independent predictor of improved freedom from biochemical failure.
- These results demonstrate that brachytherapy is acceptable for men with intermediate-risk prostate cancer, demonstrating improved freedom from biochemical failure but no effects on overall survival.