Phase II trial of abiraterone acetate (AA) treatment for metastatic prostate cancer (PC) patients with a PSA of more than four following initial androgen deprivation therapy: SWOG S1014.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 152-152
Author(s):  
Thomas W. Flaig ◽  
Catherine M. Tangen ◽  
Maha Hussain ◽  
Neeraj Agarwal ◽  
Nicholas Mitsiades ◽  
...  
Keyword(s):  
Androgen Deprivation Therapy ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Poor Response ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Psa Response ◽  
Grade 3 ◽  
Hormonal Therapies

152 Background: Metastatic PC patients with a poor response to initial androgen deprivation therapy (ADT) as reflected by a PSA > 4 ng/ml after 7 months of ADT have a poor prognosis. In the S9346 trial, about 25% of all enrolled patients had a PSA > 4 ng/ml after 7 months of ADT with a subsequent median survival (OS) of 13 months. S1014 examined the efficacy of AA in this setting. Methods: Eligible patients with metastatic PC and a PSA of > 4ng/ml between 6-12 months after starting ADT were treated with 1,000 mg of AA daily + 5 mg of prednisone twice daily. PSA could be rising or falling at the time of enrollment, but had to be > 4 ng/ml. No chemotherapy or secondary hormonal therapies were allowed, except in patients receiving an anti-androgen at the time of enrollment, who were continued on this therapy. The primary endpoint was a PSA of ≤ 0.2ng/ml within 12 months of starting AA. The null hypothesis was a 5% rate and alternative was 20%, requiring 6 or more patients with PSA < 0.2 ng/ml to conclude the regimen is promising (one-sided α=0.048, power=0.92). Results: Forty-one patients were enrolled between 7/2012 and 7/2013. One patient was deemed not analyzable due to not receiving any protocol treatment. Fourteen patients remain on treatment. Five (13%) patients achieved an undetectable PSA of ≤ 0.2ng/ml (95% CI 4%, 27%). Nine (23%) additional patients had PSA level > 0.2 but < 4 ng/ml. Twenty-one patients had no PSA response and six were not assessable and assumed to be non-responders. The median progression-free survival (PFS) was 17.4 months. There was one incident each of Grade 4 ALT elevation and rectal bleeding. Twelve patients reported Grade 3 adverse events as their worst level of severity. Conclusions: Although encouraged by 5 patients attaining “undetectable” PSA responses to AA in this poor prognosis setting, this study did not reach the protocol pre-specified level of 6 responses. OS and PFS will be updated with further follow-up. The therapy was generally well tolerated, without any clear signal of any unexpected toxicity. Clinical trial information: NCT01309672.

A retrospective study of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (GC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 138-138
Author(s):  
Raquel Castellanos ◽  
Vinicius Ernani ◽  
Ulas Darda Bayraktar ◽  
Lorraine Portelance ◽  
Alberto J. Montero ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Locally Advanced ◽  
Poor Response ◽  
Pathologic Response ◽  
Pathological Response ◽  
Curative Intent ◽  
Survival Difference ◽  
Grade 3 ◽  
Lost To Follow Up

138 Background: Perioperative chemotherapy (chemo) with ECF (epirubicin/cisplatin/5-fluorouracil) plus surgery improved survival over surgery alone in GC in the MAGIC trial. Herein we report our experience using DCF in the perioperative setting in patients (pts) with locally advanced GC. Methods: We conducted a retrospective IRB-approved study of pts with potentially resectable locally advanced GC who were treated with DCF with neoadjuvant intent. Pts received 3 cycles of preoperative (pre-op) DCF every 3 weeks, followed by surgery, then 3 cycles of postoperative (post-op) DCF. Patients with a poor pathologic response could be changed to radiation (RT) or an alternate chemo regimen postop. Results: A total of 41 pts were identified, 24 with gastric and 17 with GEJ adenocarcinoma. All pts received at least 1 cycle of DCF and 78% received at least 3 cycles pre-op. Five pts progressed during neoadjuvant DCF, 4 were unresectable by CT after neoadjuvant DCF and 2 were lost to follow-up. The remaining 30 pts had surgery with curative intent. Post-op, 2 pts were lost to follow-up, 12 received DCF (with 6 of these also receiving RT), 11 received a different chemo regimen due to a poor response to neoadjuvant DCF (including 6 pts who also received RT). Two pts received post-op RT only. The median PFS was 16.8 months (95% CI 7.7 - 25.9) and the median OS was 26.9 months (95% CI 18.7–35.1). The PFS was longer for pts who had a radiological or pathological response to neoadjuvant DCF (log rank p = 0.005 and 0.02 respectively) and for pts who received DCF post-op (log rank p = 0.005). Among pts who did not receive DCF post-op, there was no survival difference between the pts who were switched to an alternative chemo or chemoRT regimen post-op compared to those who received no further therapy. The most common chemo-related adverse events were anemia (27% grade 3 or 4), nausea/vomiting (17% G3 or 4), and febrile neutropenia (12%). Conclusions: The DCF regimen is well tolerated in locally advanced GC. Patients who do not have a good response (either radiologic or pathologic) to pre-op DCF appear to have a poor prognosis regardless of the post-op treatment given.

scholarly journals Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study

2020 ◽  
Author(s):  
K Kobayashi ◽  
N Okuno ◽  
G Arai ◽  
H Nakatsu ◽  
A Maniwa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

Abstract Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (&lt;4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon’s minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. Results For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55–86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4–84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%–69.3%), median prostate-specific antigen–progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). Conclusions Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen–progression-free survival was shorter than that reported in previous studies. Considering the benefit–risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 55-55
Author(s):  
Eleni Efstathiou ◽  
Vasily J. Assikis ◽  
Scott A. North ◽  
John Showel ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Psa Response ◽  
Grade 3

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of feasibility and efficacy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 310-310
Author(s):  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao ◽  
Matt D. Galsky ◽  
Richard Lorne Bakst ◽  
Robert Stewart ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Primary Endpoint ◽  
Abiraterone Acetate ◽  
Radium 223 ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3 ◽  
Additional Therapy ◽  
Clinical Trial Information

310 Background: Optimal sequencing of approved therapeutic agents in mCRPC is not known. The standard approach, is to treat until resistance then switch. The PRINT trial explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat an intrinsically heterogeneous disease, to delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients were treated with 3 consecutive treatment modules, each of 12 weeks' duration: 1. abiraterone acetate 1000 mg PO daily and prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV and carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily and radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). After completion of this 9 month regimen, patients are followed on ADT alone. Primary endpoint is PSA or radiographic time to disease progression. Results: From 3/2017 to 10/2018, 28 of 40 planned men with mCRPC were enrolled, 19 (67.9%) with bone metastases. PSA response rates ( > 90%/ > 50%), compared to baseline, following each treatment module: 1. 50%/78.6%; 2. 50%/92.7%; 3. 64.39%/92.7%. Currently, 14 patients have completed the study regimen with median follow up of 3.6 months, 8 of whom continue without any additional therapy. Of the patients evaluable for primary endpoint, median time to PSA progression is 96+ days (95% CI 82-110+ days). The regiment was well tolerated, grade 3/4 adverse effects include: hyperglycemia (17.9%), diarrhea (7.1%), anemia (3.6%), fatigue (3.6%), neutropenia (3.6%), thrombocytopenia (3.6%). Measurable response and molecular correlate data will be presented. Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen is feasible, demonstrates significant antitumor benefits, and is well tolerated. Further follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160.

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRP—Early observations of efficacy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 89-89
Author(s):  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao ◽  
Matt D. Galsky ◽  
Richard Lorne Bakst ◽  
Robert Stewart ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Radium 223 ◽  
Psa Response ◽  
Psa Progression ◽  
Therapy Completion ◽  
Grade 3 ◽  
Daily Prednisone ◽  
Clinical Trial Information

89 Background: Optimal sequencing of therapeutic agents in mCRPC remains debated, but the standard approach is to treat with one agent until resistance is met before switching. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat intrinsic heterogeneity, delay/prevent drug resistance, and minimize toxicity. Methods: Enrolled patients all received 3 consecutive treatment modules, each 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks (in those with bone metastases). Upon completion of the 9-month regimen, patients are followed on ADT alone. Primary endpoint for the study is PSA or radiographic time to progression (TTP). Results: From 3/2017 to 10/2019, 35 of 40 planned men with mCRPC were enrolled, 25 patients have completed the 9-month study regimen and evaluable for TTP analysis. With median follow up of 52 weeks, median time to PSA progression after therapy completion is 15.5 weeks (95%CI; 5-26.1+ weeks). PSA response rates show successive improvements with each sequential treatment module (Table). Six (24%) patients continue on post-study surveillance with ADT alone, two of which have remained off any mCRPC agents for over a year (64+ weeks, 54+ weeks). In patients needing to restart therapy, experience with efficacy and tolerability of each agent while on the study, has helped inform subsequent mCRPC drug selection. The study regimen is well-tolerated, with few grade 3/4 AE’s: hyperglycemia (14.3%), diarrhea (5.7%), anemia (2.9%), fatigue (2.9%), neutropenia (2.9%), and thrombocytopenia (2.9%). Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen demonstrates significant antitumor benefits, with potential for long-term suppression of disease. Further longitudinal follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160. [Table: see text]

Efficacy and Safety of Dasatinib in Patients with Chronic Myeloid Leukemia in Blast Phase Whose Disease Is Resistant or Intolerant to Imatinib: 2-Year Follow-Up Data from the START Program.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 472-472 ◽  
Author(s):  
Carlo Gambacorti ◽  
Jorge Cortes ◽  
Dong-Wook Kim ◽  
Herve Dombret ◽  
Chao Zhu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Blast Crisis ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Prior Therapy ◽  
Imatinib Resistant ◽  
Grade 3

Abstract The prognosis for patients with myeloid-blast (MB) or lymphoid-blast (LB) chronic myeloid leukemia (CML) is poor, with an estimated survival from onset of blast crisis of approximately 3 months. Dasatinib (SPRYCEL®) is a novel inhibitor of BCR-ABL and SRC-family kinases, that has proven to be effective (in terms of complete hematologic and cytogenetic response) for patients with MB- or LB-CML whose disease is either resistant or intolerant to imatinib. Patients were enrolled to the corresponding START studies between January and June 2005, and dasatinib 70 mg BID was administered to 109 patients with MB-CML and 48 patients with LB-CML. All patients had previously failed treatment with imatinib - 90% of whom were resistant to imatinib. Here we present an update with a minimum follow-up of 12 mo. Of the 157 patients, 56% were male and median age was 54 years (range 17–81). Median time from CML diagnosis was 44 mo (range 2–216). Prior therapy included imatinib >600 mg/d in 50% of patients, treatment with imatinib for >3 years in 36%, and stem-cell transplantation in 19%. At baseline, 57% had WBC <20,000/mm3, 69% had platelets <100,000/mm3, and 18% had extramedullary disease outside of the spleen. Major hematologic responses (MaHRs) were induced in 34% of patients with MB-CML (imatinib-resistant 35%, -intolerant 20%) and 35% of LB-CML patients (imatinib-resistant 36%, -intolerant 33%). Major cytogenetic responses (MCyRs) were attained in 33% of patients with MB-CML (imatinib-resistant 34%, -intolerant 20%) and 52% of LB-CML patients (imatinib-resistant 50%, -intolerant 67%), while complete cytogenetic responses (CCyRs) were achieved in 26% (imatinib-resistant 26%, -intolerant 20%) and 46% of patients (imatinib-resistant 43%, -intolerant 67%), respectively. Median progression-free survival was 6.7 mo (MB-CML) and 3.0 mo (LB-CML) while median overall survival was 11.8 mo and 5.3 mo, respectively. Dasatinib was generally well tolerated in this poor prognosis population. Fluid retention events were observed more frequently in the MB-CML cohort, with all grade pleural effusion occurring in 36% and 13% of MB and LB patients, respectively (grade 3–4 - 15% and 6%). Other non-hematologic side effects were primarily grade 1–2. Cytopenias were noted for the majority of patients, and were manageable; grade 3–4 febrile neutropenia was recorded in 8% of patients. Dasatinib doses were reduced in 32% of patients and interrupted in 59%, most typically as a result of non-hematologic toxicities. Doses were escalated in 44% of patients. The median duration of therapy was 3.4 mo (0.03–18) for all patients and 14 mo (6–18) for patients still receiving treatment. Long-term data confirm that dasatinib is highly active, producing rapid and clinically meaningful responses in this poor prognosis patient population. Updated analyses corresponding to a minimum follow-up of 2 years on all patients will be presented.

Phase II multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
C. Ryan ◽  
E. Efstathiou ◽  
M. Smith ◽  
M. Taplin ◽  
G. Bubley ◽  
...  
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Androgen Withdrawal ◽  
Psa Response ◽  
Grade 3 ◽  
Hormonal Therapies ◽  
Ecog Ps

5046 Background: AA is a potent inhibitor of the enzyme CYP17, a major contributor to androgen biosynthesis. Keto is also known to inhibit this enzyme but AA is many-fold stronger in its action. 33 pts with progressive metastatic disease, normal organ function, ECOG performance status (PS) 0–1, and no prior chemo were enrolled. Pts with prior keto treatment were excluded. AA (1000 mg qd) plus prednisone (5mg bid) were administered orally in 28 day cycles. Methods: Results: At baseline median age was 71.0 (range 52–85) yrs and median PSA was 24.7 (range 7.1–1110.0) ng/mL;19/26 pts (73%) had an ECOG PS of 0 and 7/26 (27%) had PS of 1; the median number of prior hormonal therapies was 2; all pts were on LHRHa and 73% of pts had received anti-androgen, all of whom had undergone prior anti-androgen withdrawal. Pts were evaluated at each cycle for PSA response according to PSAWG criteria. 27 pts have available data for PSA response. Total maximal PSA declines of ≥30%, ≥50%, ≥90% were observed in 89% (24/27), 85% (23/27) and 41% (11/27) pts, respectively. Week 12 PSA declines displayed a similar and sustained trend: ≥30%, ≥50% and ≥90% PSA decline in 82%, 78%, and 26% of pts. Post-treatment ECOG PS score was 0 in 24 (92%) pts: 19% experienced improvement in PS (PS 1 to 0 in 5 pts) and 19/19 pts maintained a PS of 0; Median time to PSA progression has not been reached. Majority of adverse events were grades 1–2. Incidence of hypokalemia - 12%; HTN - 6%; edema - 15%. One pt experienced a grade 3 drug-related HTN. Conclusions: Abiraterone acetate plus prednisone has significant anti-cancer activity in patients with metastatic CRPC not previously treated with ketoconazole or chemotherapy, as demonstrated by declines in PSA and improvement in performance status, and is well-tolerated. [Table: see text]

Results of a phase II study of sunitinib (SU) maintenance after response to docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 153-153 ◽  
Author(s):  
Bernhard J. Eigl ◽  
Misha Eliasziw ◽  
Scott A. North ◽  
Marc G. Trudeau ◽  
Eric Winquist ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

153 Background: Docetaxel (D) remains the standard first cytotoxic therapy in mCRPC. Given its mechanism of action, acceptable toxicity profile and simple administration, SU had potential as maintenance therapy for mCRPC. In this multicenter study, we evaluated the tolerability and efficacy of SU monotherapy in patients (pts) with mCRPC who have responded to D. Methods: Pts withmCRPC and responding/stable disease at the time of D completion were enrolled in this multicentre trial. Pts received 50mg of SU daily on 4/2 week on/off cycles. The primary endpoint was progression-free survival (PFS), defined on the basis of RECIST criteria and worsening disease-related symptoms requiring further therapy. Because the effect of SU on PSA is not well known, PSA progression alone was not considered disease progression. PFS of 180 days was considered to be a clinically meaningful threshold for recommending further study of SU. PSA response was a secondary endpoint. The threshold for PSA-progression (PSA-P) was defined as a 25% increase in PSA over baseline. Results: Twenty-three pts were enrolled and treated. Mean age was 66.5 years (48-78). ECOG scores of 0, 1, and 2 were reported for 9, 13 and 1 pts respectively. Mean number of prior cycles of D was 8.6 (4-12). A total of 92 cycles of SU were administered; a mean of 4 per pt (1-11). Mean follow-up was 5.4 months (0.6-15). A total of 479 adverse events (AE) were recorded, of which 88% were Grade 1-2 and 12% were Grade 3-4. The AE were of a type and severity expected for SU. Three Grade 4s occurred, consisting of hepatitis, myelosuppression, and pneumonia. Median PFS was 133 days (95% CI: 48-154). Most pts had immediate PSA increases without evidence of disease progression, with the mean increases in PSA over baseline being 197%, 342%, and 1437% in Cycles 1, 2, and 3, respectively (p<0.05). Conclusions: Although SU was well tolerated as maintenance therapy with predictable side-effects, median PFS was lower than the predefined threshold of 180 days. PSA values were not informative as significant increases were observed as early as Cycle 2. This agent is not considered worthy of further investigation in this setting of maintenance therapy. Clinical trial information: NCT00550810.

Baseline circulating tumor cell (CTC) count as a prognostic marker of PSA response and progression in metastatic castrate sensitive prostate cancer (mCSPC): Results from SWOG S1216, a phase III randomized trial of androgen deprivation plus orteronel (cyp17 inhibitor) or bicalutamide.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5506-5506
Author(s):  
Amir Goldkorn ◽  
Catherine Tangen ◽  
Melissa Plets ◽  
Gareth Morrison ◽  
Alexander Cunha ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Circulating Tumor Cell ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Psa Response ◽  
Castrate Resistant ◽  
Hormonal Therapies

5506 Background: In mCSPC, androgen deprivation therapy (ADT) combined with chemotherapy or androgen receptor signaling inhibition (ARSI) is the new standard of care. Biomarkers that predict clinical outcomes with these therapies are needed. We hypothesized that CellSearch CTC count, an FDA-cleared biomarker in metastatic castrate resistant PC (mCRPC), may be a valuable biomarker in mCSPC. Methods: In S1216, peripheral blood was drawn with informed consent at registration (baseline), and CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini) per standard manufacturer protocol. CTC counts were analyzed centrally for associations with 2 pre-specified trial intermediate endpoints: 7-month PSA (7mPSA) ≤ 0.2 ng/ml vs. 0.2–4.0 vs. > 4.0, (intermediate endpoint for overall survival, OS); and progression-free survival (PFS) < vs. > 2 years. Because OS data have not matured, analysis was pooled and equal numbers of samples were analyzed from each treatment arm and outcome measure (7mPSA and PFS) as stipulated by the Data Safety Monitoring Committee. Results: From 2014 to 2017, 523 baseline samples were collected. In the 7mPSA analysis (n = 264), CTCs were detected in 38% of men, with a median of 4 CTCs in those with detectable CTCs. In the PFS analysis (n = 336), CTCs were detected in 37% of men, with a median of 3 CTCs in those with detectable CTCs. Adjusting for disease burden (minimal vs. extensive) and ADT status (already initiated or not) at the time of CTC measurement, men with undetectable CTCs were 6.1-fold more likely to attain 7mPSA ≤ 0.2 (OR 6.1, 95% CI 2.1-17.2, p < 0.001) and 3.7-fold more likely to achieve > 2 years PFS (OR 3.7, 95% CI 1.7-8.1, p < 0.001) compared to men with baseline CTCs ≥ 5. Other cutpoints previously validated in mCRPC studies (CTC < 5 vs. ≥5 and CTCs 0 vs. ≥1) also strongly discriminated 7mPSA and PFS with statistical significance in this mCSPC cohort. Conclusions: CTC count at the start of treatment for mCSPC was highly prognostic of 7-month PSA response (intermediate endpoint for OS) and of PFS at 2 years. To our knowledge, this is the first such strong evidence from a prospective phase 3 trial of this magnitude. Additional analyses are planned when the trial is fully reported. Baseline CTC count may serve as a valuable prognostic marker to discriminate men likely to respond favorably to hormonal therapies from those who may benefit from early alternate interventions.

Phase II randomized study of abiraterone acetate plus prednisone (AAP) added to ADT versus apalutamide alone (APA) versus AAP+APA in patients with advanced prostate cancer with noncastrate testosterone levels: (LACOG 0415).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5505-5505
Author(s):  
Fernando C. Maluf ◽  
Andre P. Fay ◽  
Vinícius Carrera Souza ◽  
Fabio A. B. Schutz ◽  
Oren Smaletz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Treatment Options ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Biochemical Relapse ◽  
Testosterone Levels ◽  
Psa Response ◽  
Grade 3

5505 Background: ADT combined with AAP, APA, enzalutamide or docetaxel are among the standard treatment options to patients (pts) with hormone sensitive advanced/metastatic prostate cancer (PC). However, treatment-related adverse events (TRAEs) due to ADT impact negatively on the quality of life of these patients. Effective options with fewer TRAEs are required. Methods: LACOG 0415 is a phase II, randomized trial (1:1:1) evaluating the use of AA 1000mg po + prednisone 5mg po BID + ADT versus APA 240mg po alone versus AA 1000mg po + prednisone 5mg po BID + APA 240mg po in patients with advanced PC with non-castrate testosterone levels and indication of ADT (N+ or M+ or biochemical relapse combined with PSA ≥ 20 ng/ml or with PSA≥4 ng/ml and PSA doubling-time < 10 months). Stratification factors: metastatic disease (+/-). Primary endpoint was the percentage of pts who achieved PSA ≤ 0.2 ng/mL at Week 25, we estimated a PSA response rate of 65% in each of the three arms with a null hypothesis of 45%, power of 80% and alfa 5%, using Fleming one-stage method. Secondary endpoints were percentage of pts with ≥ 80% and ≥ 50% decline in PSA at week 25, radiographic progression-free survival (rPFS) and safety. Results: 128 patients were randomized between Oct 2017 and Apr 2019, and 122 pts were evaluable for PSA response. Median age was 69y (range, 53-88); most pts had ECOG PS0-1(99%). 17% of pts had biochemical relapse only, 9% N+ and 74% M+ disease. At week 25 the PSA was ≤ 0.2 ng/mL in 76% of pts in AAP+ADT arm, 59% in APA, and 80% in APA+AAP. All pts had a decline of ≥ 50% in PSA at week 25. 97% had a decline of ≥ 80% in PSA at week 25: 100% of pts in AAP+ADT arm, 95% in APA and 98% in APA+AAP. A total of 3 pts had clinical progressive disease, one in each arm. Two of them also had radiological progression at week 25, 1 pt in AAP+ADT arm and 1 pt in APA. TRAEs rates of any grade were 71% in AAP+ADT arm, 64% in APA, and 65% in APA+AAP. TRAEs rates of Grade≥3 were 12% in AAP+ADT arm, 9% in APA and 16% in APA+AAP. 9 pts (7%) discontinued the treatment before the week 25, 5(4%) of them due to toxicity: 1 pt from AAP+ADT, 2 pts from APA, and 6 pts from APA+AAP. Conclusions: The AAP+ADT and APA+AAP groups showed high effectiveness in terms of PSA response. Radiologic disease control and the decline of ≥ 80% in PSA at week 25 were similar among all treatment arms. APA alone had less toxicity. APA+AAP and APA alone are promising regimens in this setting. No new safety signal was detected in the study. Clinical trial information: NCT02867020 .

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