Efficacy and safety in older patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone (ABI) or enzalutamide (ENZ) in the CARD study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5559-5559 ◽  
Author(s):  
Cora N. Sternberg ◽  
Daniel Castellano ◽  
Johann S. De Bono ◽  
Karim Fizazi ◽  
Bertrand F. Tombal ◽  
...  
Keyword(s):  
Disease Progression ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Previously Treated ◽  
Grade 3 ◽  
Post Hoc ◽  
The Impact ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

5559 Background: In the CARD (NCT02485691) study, radiographic PFS (rPFS), PFS and OS were significantly improved with CBZ vs. androgen-signaling-targeted agents (ARTA; ABI or ENZ) in pts with mCRPC who had received docetaxel (DOC) and progressed within 12 months (mo) on an alternative ARTA. This analysis evaluated the impact of age (< 70 vs. ≥ 70 years) on the efficacy and safety of CBZ and ARTAs in CARD. Methods: 255 pts with mCRPC were randomized 1:1 to CBZ (25 mg/m2 IV Q3W + prednisone [P] + G-CSF) vs. ABI (1000 mg PO + P) or ENZ (160 mg PO) until disease progression, unacceptable toxicity or pt request. Pts were eligible if they had received ≥ 3 cycles of DOC and progressed ≤ 12 mo on the previous alternative ARTA. Primary endpoint was rPFS. Subgroup analysis of older (≥ 70 years; n = 135) and younger (< 70 years; n = 120) pts was pre-specified for rPFS; others were post hoc. Results: rPFS was significantly improved vs. ARTA in both older (median 8.2 vs. 4.5 mo; HR 0.58; 95% CI 0.38–0.89) and younger pts (median 7.4 vs. 3.2 mo; HR 0.47; 95% CI 0.30–0.74). Median OS for CBZ vs. ARTA was 13.9 vs. 9.4 mo (HR 0.66; 95% CI 0.41–1.06) in older pts and 13.6 vs. 11.8 mo (HR 0.66; 95% CI 0.41–1.08) in younger pts. PFS, tumor, PSA and pain responses also favored CBZ, regardless of age. Grade ≥ 3 adverse events (AEs) occurred in 57.8% vs. 49.3% of older pts receiving CBZ vs. ARTA and 48.4% vs. 42.1% in younger pts. AEs leading to death were more frequent with ARTA, mainly due to disease progression. Conclusions: CBZ had improved efficacy outcomes vs. ARTA in pts with mCRPC previously treated with DOC and the alternative ARTA, regardless of age. Grade ≥ 3 cardiac AEs were more frequent in older pts treated with ARTA. A higher rate of AEs was reported in older vs. younger pts, for ARTA and CBZ. CBZ and ARTA had different safety profiles in older compared with younger pts. Clinical trial information: NCT02485691 . Funding: Sanofi. [Table: see text]

Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 104-104 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Josep M. Piulats ◽  
Marine Gross-Goupil ◽  
Jeffrey C. Goh ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Response Rate ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

104 Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]

Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Howard I. Scher ◽  
Karim Fizazi ◽  
Fred Saad ◽  
Kim N. Chi ◽  
Mary-Ellen Taplin ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Post Hoc Analysis ◽  
Castration Resistant ◽  
Study Results ◽  
Psa Progression ◽  
Grade 3 ◽  
Post Hoc ◽  
The Impact

6 Background: ENZA increased median overall survival (OS) by 4.8 mo (P <0.001, HR 0.63) vs placebo (PBO) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) post-docetaxel in AFFIRM (HI Scher et al, NEJM 2012). Corticosteroids (CS) can activate AR signaling in nonclinical models (J Richards, Can Res 2012). In a multivariate model of AFFIRM data baseline CS use was associated with reduced OS (HI Scher et al. ESMO 2012 abstract 899PD). The impact of CS use during study treatment in AFFIRM was evaluated to test if concomitant CS use is also associated with inferior outcomes. Methods: Pts were randomized 2:1 to ENZA 160 mg/d or PBO. Pts were allowed but not required to take CS. OS was the primary endpoint. In a post-hoc analysis On-study CS use was defined as oral CS user for ≥ 1 day on study. Results: On study CS use was 48% in ENZA and 45% in PBO pts. Prognostic factors were slightly better in the no CS group compared to the CS group. Use of CS regardless of treatment was associated median OS of 11.5 mo (95% CI: 10.5, 13.0) for CS pts vs median OS NM (NM, NM) for no CS pts (HR=0.40; 95% CI: 0.33, 0.48). ENZA was consistently superior to PBO for OS, radiographic progression free survival (rPFS) and time to PSA progression (TTPP), regardless of CS use (Table). Pts on CS had higher rates of grade 3 - 4 adverse events (AE) compared to no CS pts: 63.3% vs 34.4% respectively. Conclusions: In this post-hoc analysis, on study CS use was associated with reduced OS and higher rates of grade 3 -4 AEs in mCRPC pts post-docetaxel. While CS pts had worse outcomes, ENZA was consistently superior to PBO regardless of on study CS use. The inferior outcomes in CS pts may be due to unmeasured confounders or the biologic properties of CS use itself. Clinical trial information: NCT00974311. [Table: see text]

Pembrolizumab for metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Updated analysis of KEYNOTE-199.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Jeffrey C. Goh ◽  
Marine Gross-Goupil ◽  
Ulka N. Vaishampayan ◽  
Josep M. Piulats ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Toxicity Response ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

216 Background: Previously presented data from cohorts (C) 1-3 of the phase 2 KEYNOTE-199 study (n = 258; NCT02787005) showed that pembrolizumab monotherapy had antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with next-generation hormonal agents (NHAs; eg, abiraterone, enzalutamide) and docetaxel. Activity was observed for both PD-L1–positive and negative cohorts and in RECIST-measurable and bone-predominant disease. We present data from KEYNOTE-199 C1, C2, and C3 based on longer-follow-up. Methods: C1 enrolled 133 pts with RECIST-measurable, PD-L1–positive disease, C2 enrolled 66 pts with RECIST-measurable, PD-L1–negative disease, and C3 enrolled 59 pts with nonmeasurable, bone-predominant disease. All pts had ECOG PS 0-2 and received ≥1 NHA and 1-2 prior chemotherapies including docetaxel. Pembrolizumab 200 mg Q3W was given for 35 cycles or until PD or intolerable toxicity. Response was assessed Q9W in yr 1, then Q12W. Primary end point was ORR per RECIST v1.1 by central review. Key secondary end points included DCR (CR + PR + SD ≥6 mo), duration of response (DOR), OS, and safety. Results: Median follow-up as of Aug 21, 2018, was 9.5 mo in C1, 7.9 mo in C2, and 14.1 mo in C3. ORR (95% CI) was 5% (2-11) in C1 and 3% ( < 1-11) in C2. DCR was 10% in C1, 9% in C2, and 22% in C3 per RECIST v1.1. Median (range) DOR was not reached (1.9-21.8+ mo) in C1 and 10.6 mo (4.4-16.8) in C2; KM estimates of DOR ≥12 mo were 71% and 50%. Median (95% CI) OS was 9.5 mo (6.4-11.9) in C1, 7.9 mo (5.9-10.2) in C2, and 14.1 (10.8-17.6) in C3. 12-mo OS rates were 41% in C1, 35% in C2, and 62% in C3; 18-mo rates were 30%, 21%, and 36%. Grade 3-5 drug-related AE rates were 15% in C1, 14% in C2, and 17% in C3. There were 2 drug-related deaths (n = 1 each sepsis and pneumonitis). Conclusions: Pembrolizumab shows antitumor activity and disease control with acceptable safety in RECIST-measurable and bone-predominant mCRPC previously treated with NHAs and docetaxel. Responses are durable, and the observed OS benefit is promising. Clinical trial information: NCT02787005.

Experience with sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) with visceral spread from PROCEED.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 174-174
Author(s):  
Nicholas J. Vogelzang ◽  
Philip W. Kantoff ◽  
Mark C. Scholz ◽  
Jeffrey L. Vacirca ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Cellular Immunotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant ◽  
Visceral Metastases ◽  
Antigen Presenting ◽  
Post Hoc ◽  
Clinical Trial Information

174 Background: Trials of approved agents in mCRPC have reported shorter overall survival (OS) in men with visceral metastases (mets). The phase 3 IMPACT trial evaluated sipuleucel-T, an autologous cellular immunotherapy, in mCRPC but excluded visceral mets. PROCEED, a registry of mCRPC patients receiving sipuleucel-T, offers the first description of sipuleucel-T in patients with visceral mets. Methods: PROCEED enrolled men with mCRPC treated with sipuleucel-T biweekly x 3. Dose adjustment for organ dysfunction was unnecessary. Men were followed until death, study withdrawal, or a minimum of 3 years. OS is reported in this post-hoc subgroup analysis. Results: 1902 men received ≥1 sipuleucel-T infusion between 2011-2014. Visceral mets (n = 90) included liver (n=21), lung (n=61), and brain (n=2) involvement. Compared to patients without visceral mets (Table), men with visceral mets had poorer performance status (PS) and higher baseline prostate-specific antigen (PSA). Median OS was 20.5 and 31.2 mo in those with and without visceral mets. Patients with liver and lung mets had a median OS of 16.3 and 21.0 mo, respectively. Activation of antigen-presenting cells, a measure of immune activation and product potency, was similar in those with and without visceral mets. Conclusions: Initial observations suggest that patients with mCRPC and visceral spread can activate their immune cells to produce sipuleucel-T, but have a shorter OS than those with bone and/or lymph node spread. (NCT01306890). Clinical trial information: NCT00065442. [Table: see text]

ModraDoc006, an oral docetaxel formulation in combination with ritonavir (ModraDoc006/r), in metastasized castration-resistant prostate cancer (mCRPC): A multicenter phase I study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 79-79
Author(s):  
Marit Vermunt ◽  
Debbie Robbrecht ◽  
Lot Devriese ◽  
Julie Janssen ◽  
Marianne Keessen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3 ◽  
Weekly Cycles ◽  
Dose Levels ◽  
Anti Tumor Activity

79 Background: ModraDoc006 is a novel formulation of docetaxel and to enhance bioavailability, this tablet is co-administered with ritonavir (r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The safety, anti-tumor activity and pharmacokinetics (PK) of ModraDoc006/r were investigated by dose-escalation in patients with mCRPC, to propose a recommended phase 2 dose (RP2D). Methods: Progressive mCRPC patients, who were treatment naïve or previously treated with either abiraterone or enzalutamide, received a maximum of 30 weekly cycles of ModraDoc006/r in a bi-daily once weekly (BIDW) schedule. Plasma docetaxel concentrations were determined at the first 2 cycles up to 48h after intake of ModraDoc006/r. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Serum Prostate Specific Antigen (PSA) levels were assessed every 6 weeks. Results: 23 patients were included, of whom 20 were evaluable for safety and PK. In 5 patients, the initial 30-20/100-100 dose was explored, with observation of one dose limiting toxicity (DLT) (grade 3 alanine aminotransferase increase). The next dose level of 30-20/200-200 resulted in 2 DLTs in 6 patients (grade 3 diarrhea and mucositis). Subsequently, two intermediate dose levels: 30-20/200-100 and 20-20/200-100 were explored in 6 and 3 patients. At the 30-20/200-100 dose, an adequate docetaxel exposure was achieved and 1 DLT (grade 3 diarrhea) was observed, with no DLTs at the 20-20/200-100 dose. Common treatment-related AEs (occurring in > 30% of all patients) were diarrhea, nausea, vomiting, anorexia and fatigue. Five patients completed the maximum of 30 weekly treatments. In 10 patients, evaluable for anti-tumor activity after treatment with ≥9 cycles, 4 confirmed and 2 non-confirmed PSA responses ( > 50% decrease) were observed. Conclusions: The RP2D of BIDW ModraDoc006/r in mCRPC was established as 30-20/200-100 mg. These results are encouraging for further development of ModraDoc006/r as a convenient, safe and effective alternative to IV docetaxel for mCRPC patients. A phase 2b study is currently being conducted. Clinical trial information: NCT03136640.

Randomized phase II trial of docetaxel plus prednisolone with or without androgen deprivation treatment in castration-resistant prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 217-217
Author(s):  
Jae Ho Jeong ◽  
Hyejung Hyun ◽  
In Gab Jeong ◽  
Jun Hyuk Hong ◽  
Hanjong Ahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Outcomes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
Psa Progression ◽  
The Impact ◽  
Clinical Trial Information

217 Background: Androgen deprivation therapy (ADT) has been the main treatment option for patients with locally advanced or metastatic prostate carcinoma. However, the impact of continued ADT on clinical outcomes in castration-resistant prostate cancer (CRPC) patients treated with cytotoxic chemotherapy is controversial. We conducted a randomized phase II study to assess the impact of continued ADT in patients with CRPC receiving docetaxel plus prednisolone chemotherapy. Methods: Patients with CRPC were randomly assigned (in a 1:1 ratio) to receive docetaxel (75mg/m2 every 3 weeks) plus prednisolone (5mg twice daily on days 1-21) with ADT (leuprolide 11.25 mg long-acting depo every 12 weeks, ADT group) and docetaxel plus prednisolone without ADT (No-ADT group). For patients in the No-ADT group, ADT was resumed at the end of chemotherapy. The primary endpoint was time to PSA progression. Secondary objectives included PSA response rates, progression-free survival (PFS), and overall survival (OS). Suspension of leuprolide support prevented the attainment of our original goal of enrolling 80 men. Results: Between April 2011 and July 2014, 45 patients were enrolled in this study; 23 patients were randomly assigned to the ADT group and 22 to the No-ADT group. The median age was 68 years (range = 49-81) and median baseline serum PSA was 60.3 ng/mL (interquartile range = 14.7-157.3). Time to PSA progression was 6.5 months in ADT group and 4.3 months in No-ADT group, respectively (P = 0.673). PSA response rates were 55.2% and 44.8% in the ADT group and the No-ADT group, respectively (P = 0.463). The median PFS and OS were 5.3 months and 19.4 months for ADT patients and 4.3 months and 20.8 months for No-ADT patients, respectively (P = 0.608, P = 0.635). The testosterone level rose to more than the castrate level in 5 (22.7%) patients of the No-ADT group. Conclusions: Clinical outcomes were not significantly different when patients with CRPC received concurrent ADT, or were not so treated, when receiving docetaxel plus prednisolone chemotherapy. Clinical trial information: NCT01487902 Clinical trial information: NCT01487902.

A clinical study to evaluate the efficacy and safety of docetaxel with ribavirin in patients with progressive castration resistant prostate cancer who have previously received docetaxel alone.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14010-e14010 ◽  
Author(s):  
Takeo Kosaka ◽  
Takahiro Maeda ◽  
Toshiaki Shinojima ◽  
Hirohiko Nagata ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Clinical Study ◽  
Adverse Events ◽  
Disease Progression ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Grade 3

e14010 Background: We have previously reported a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting cancer stemness related gene network and identified ribavirin as a candidate drug for overcoming docertaxel resistant castration resistant prostate cancer.This non-randamized and open-labelled pilot clinical study explored the safety and efficacy of ribavirin, anti-virus drug, in combination with docetaxel in patients with progressive CRPC. Methods: In this clinical study, patients received intravenous docetaxel 60-70 mg/mm2 on day 1 of 3-6 weeks cycles plus Ribavirin 600 mg twice daily. The primary endopoint was safety, PSA response and objective response rate. Secondary end ponts included health-related quality of life overall survival.Patients with progressive CRPC based on PSA and/or radiographic criteria, PS 0-1, normal renal and hepatic function were eligible. Results:Five patients were enrolled in this study. Medium age was 73. Median serum PSA concentration was 53.1 ng/ml (range: 5.1-370.5).The median cycle and total dose of docetaxel received before the study was 31 cycles and 3625 mg, respectively. 80% of patients who had disease progression during docetaxel treatment. The median time from last docetaxel dose to disease progression before the participation was 1.5 months.Safety: Medium number of treatment cycles were 7 (range: 3-8) cycles. Grade 3/4 adverse events requiring dose modification were not observed. Grade 3 anemia and neutropenia were seen in two patients. Common adverse events were less than Grade 2. Efiicacy: 3 (60%) had some degree of PSA decline and 2 (40%) had a decline of ≧30 %. Median follow-up was 10.0 month. Median progression free survival was 6 month. Conclusions: This combination was well tolerated with promising response rate, justifying further investigation in docetaxel resistant CRPC. Clinical trial information: UMIN000012521.

Efficacy of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and baseline (BL) comorbidities (CM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Proportional Hazards Models ◽  
Castration Resistant ◽  
Cox Proportional Hazards Models ◽  
The Impact ◽  
Clinical Trial Information

5023 Background: The addition of APA to ongoing ADT in pts with nmCRPC significantly prolonged metastasis-free survival (MFS), time to symptomatic progression (SymProg), and second progression-free survival (PFS2) in SPARTAN. We assessed the impact of APA on these end points in pts with or without BL CM. Methods: Using Cox proportional hazards models, treatment effect of APA was evaluated in SPARTAN pts with CM at BL, stratifying by the presence of BL diabetes/hyperglycemia (D/H), cardiovascular disease (CVD), hypertension (HTN), and renal insufficiency (RI). Results: Of 1207 SPARTAN pts, 1062 (88%) had ≥ 1 BL CM, including 703/806 (87%) APA pts and 359/401 (90%) PBO pts. A total of 226 (19%), 398 (33%), 798 (66%), and 774 (64%) pts had D/H, CVD, HTN, and RI, respectively; 323 (27%), 412 (34%), 259 (21%), and 68 (6%) pts had 1, 2, 3, and 4 CM, respectively. Incidence of CM was balanced between arms. Pts with CM were older than pts with no CM (median age, 75 vs 69 yrs, APA; 74 vs 69 yrs, PBO). MFS, SymProg, and PFS2 benefit with APA was significant in all CM subgroups, except PFS2 for pts with D/H (Table) and regardless of the number of CM. The incidence of any treatment-emergent AE was balanced between pts with and without CM. AEs with APA were not affected by any CM. Clinical trial information: NCT01946204. Conclusions: The benefit of APA + ongoing ADT in pts with nmCRPC was maintained in pts with D/H, CVD, HTN, and RI. The safety profile of APA was not affected by any CM.[Table: see text]

KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New data after an additional 1 year of follow-up.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 10-10
Author(s):  
Leonard Joseph Appleman ◽  
Michael Paul Kolinsky ◽  
William R. Berry ◽  
Margitta Retz ◽  
Loic Mourey ◽  
...  
Keyword(s):  
Oral Prednisone ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Psa Response ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Grade 3

10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

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