Phase II study of docetaxel-prednisone (DP) in combination with metronomic cyclophosphamide (CTX) and celecoxib (C) as first-line treatment in castration resistant prostate cancer (CRPC) patients (Pts)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16032-e16032
Author(s):  
A. Fontana ◽  
G. Bocci ◽  
L. Galli ◽  
L. Derosa ◽  
G. Minuti ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Median Number ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Peripheral Blood Mononuclear ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

e16032 Background: Metronomic oral CTX and C has demonstrated activity and a favourable toxicity profile in CRCP. Combination of such strategy with the standard DP could be of interest. Methods: Pts with CRPC received D 60 mg/sqm iv day 1 every 3 weeks up to 12 cycles and from day 2 continuously: P 5 mg po BID, CTX 50 mg po daily, and C 200 mg po BID. Primary objective is the percentage of pts free of progression at 6 months; secondary are: PSA levels decrease ≥ 50%, objective responses (RECIST), toxicities (NCI-CTC criteria) survival and pharmacodynamic evaluations. Results: To date 29 pts have been enrolled. Main pts characteristics are: median age 72 years (52–78 years), median PS 0 (0–2), median baseline PSA level 38,8 ng/mL (2.5–1309 ng/mL); main sites of disease: bone 23 pts (79%), lymphnodes 6 pts (21%), liver 1 pt (3,5%). Twenty-nine pts are evaluable for toxicity whereas 28 for PSA response (1 pt abandoned the study due to allergic reaction after first D administration). Median number of D cycles delivered is 10 (1–12) and median duration of metronomic CTX plus P and C is 224 days (35–874 days). Main grade 3 side-effects are: neutropenia (2 pt; 7%), thrombocytopenia, diarrhoea, stomatitis and onycholysis (1 pt; 3.5%). No grade 4 toxicities have been observed.The rate of pts free of progression at 6 months is 80%. Overall 18 pts (64%) showed a PSA decrease ≥ 50% and 23 pts (82%) showed any PSA decrease from baseline (range: 4%-99%of decrease). Four pts are evaluable according to RECIST criteria: we observed 1 CR, 2 SD and 1 PD. At a median follow up of 12,4 months median time to PSA progression is 11.6 months (95% CI 8,3–15). Conclusions: Metronomic CTX plus C in combination with DP is a feasible and tolerable regimen with a promising preliminary activity. The evaluation of plasma levels of thrombospondin-1 (TSP-1), VEGF, sVEGFR-2, VE-cadherin mRNA, and the expression of TSP-1 and VEGF in peripheral blood mononuclear cells, as potential surrogated markers of antiangiogenic activity of the combination, is ongoing. No significant financial relationships to disclose.

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.

Activity of gemcitabine-oxalipaltin (GemOx) plus prednisolone in patients with castration-resistant prostate cancer (CRPC) for whom docetaxel-based chemotherapy failed.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 108-108
Author(s):  
Jae-Lyun Lee ◽  
Yesul Kim ◽  
Jin-Hee Ahn ◽  
MeeKyung Choi ◽  
Seung-Woo Hong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Drug Effects ◽  
Fixed Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

108 Background: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of GemOx in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity in LNCaP, PC3 and DU145 cell lines. The combined drug effects were evaluated using the Chou and Taladay analysis. Clinically, patients with CRPC who failed prior docetaxel chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2/min) and oxaliplatin 100 mg/m2 intravenously every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerability develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate (PCWG 1.0 criteria). Results: The IC50of gemcitabine and oxaliplatin were, respectively, 1.25 μM and 0.69 μM for LNCaP cells; 50.00+ μM and 12.81 μM for PC3 cells; and 11.23 μM and 11.04 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 31 patients were accrued. At the time of this analysis 7 patients were still continuing treatment. The median age was 67 years (range 57 ~ 81) and the median dose of docetaxel exposure was 525 mg/m2. A total of 231 cycles administered with a median of 9 cycles per patient. PSA responses were observed in 52% (95% CI, 34~69) and partial responses were observed in 7 of 10 patients with measurable disease. Out of 23 patients, 10 patients achieved pain response (44%). With a median FU duration of 8.0 months, the median time to PSA progression was 6.4 months (95% CI, 3.5~9.2). Peripheral neuropathy developed in 78% of patients but remained of grade 1 ~2 intensities. Frequently observed grade 3 or 4 toxicities were neutropenia (10%), thrombocytopenia (10%), anemia (3%), and diarrhea (3%). Conclusions: GemOx is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720). Clinical trial information: NCT01487720.

Pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-199 cohorts 4-5.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 15-15 ◽  
Author(s):  
Julie Nicole Graff ◽  
Emmanuel S. Antonarakis ◽  
Christopher J. Hoimes ◽  
Scott T. Tagawa ◽  
Clara Hwang ◽  
...  
Keyword(s):  
Study Cohort ◽  
Topical Steroids ◽  
Castration Resistant Prostate Cancer ◽  
Fisher Syndrome ◽  
Castration Resistant ◽  
Phase 2 Study ◽  
Measurable Disease ◽  
Psa Response ◽  
Grade 3

15 Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study. Cohort (C)4 (RECIST-measurable disease) and C5 (bone-predominant disease) consist of chemotherapy-naive patients (pts) with mCRPC treated with enza + pembro after progression with enza. Results for C4 and C5 presented. Methods: Pts with or without prior abiraterone had clinically meaningful response/benefit to enza followed by disease progression. Pts received pembro 200 mg Q3W with continuation of enza for up to 35 cycles or until progression/intolerable toxicity. Primary end point: ORR, blinded independent central review (C4). Secondary end points: DCR, PSA response rate (≥50% reduction), rPFS, OS, and safety (C4, C5); DOR (C4). Results: Of 126 pts (C4, 81; C5, 45), 107 discontinued, primarily due to progression. Median follow-up: 13.7 mo (C4, 11.8; C5, 18.6). ORR (95% CI) for pts with measurable disease was 12% (6-22) in C4; DCR for all pts: 51% (39-62) in C4 and 51% (36-66) in C5 (Table). Any grade/grade 3-5 treatment-related AEs occurred in 75%/26% pts in C4 and 69%/24% in C5. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%). All except one pt (grade 3 treated with IV steroids) were treated with oral/topical steroids or had no intervention. Conclusions: Addition of pembro to enza following enza resistance showed modest antitumor activity in pts with RECIST-measurable and bone-predominant mCRPC. Combination had manageable safety and is being evaluated in a phase 3 trial. Clinical trial information: NCT02787005. [Table: see text]

Cabazitaxel multiple rechallenge in metastatic castration-resistant prostate cancer: A therapeutic option to increase overall survival?

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 97-97
Author(s):  
Cedric Pobel ◽  
Edouard Auclin ◽  
Diego Teyssonneau ◽  
Brigitte Laguerre ◽  
Mathilde Cancel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]

Clinical validation of circulating cytokines as markers of prognosis and response to docetaxel in men with metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 230-230 ◽  
Author(s):  
Kate Lynette Mahon ◽  
Hui-Ming Lin ◽  
Michelle Lee-Ng ◽  
Martin R. Stockler ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Validation Cohort ◽  
External Validation ◽  
Elisa Assay ◽  
Castration Resistant Prostate Cancer ◽  
Internal Validation ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Level 2

230 Background: Elevated circulating macrophage inhibitory cytokine -1 /growth differentiation factor 15 (MIC-1/GDF15), interleukins 4 (IL4) and 6 (IL6) levels were associated with poor prognosis and resistance to docetaxel chemotherapy in an exploratory cohort of men with metastatic castration resistant prostate cancer (mCRPC). To establish level 2 evidence of biomarker utility, these cytokines were tested in internal and external validation cohorts. Methods: Internal validation cohort: Plasma samples taken at baseline (BL) and preC2 docetaxel (n = 120). MIC-1/GDF15, IL-4 and IL-6 measured by ELISA assay. External validation cohort: Serum samples taken at BL and/or preC3 docetaxel in 430 men with mCRPC on phase III SYNERGY study (docetaxel +/- custirsen as 1st line chemotherapy in mCRPC with no OS benefit in the experimental arm). MIC-1/GDF15 measured by ELISA assay. Associations between cytokine levels, PSA response, time to PSA progression and OS were assessed by non-parametric tests and Cox Regression survival analyses. Results: Internal validation: At a median follow-up of 14 months, higher MIC-1/GDF15 levels at BL and preC2 were associated with shorter OS (BL; HR 1.2 95%CI 1.0-1.4; p = 0.03 and preC2; HR 1.3 95%CI 1.1-1.5; p = 0.004). Increase in MIC-1/GDF15 after chemotherapy correlated with lack of PSA response (p < 0.001). IL4 and IL6 did not correlate with survival or demonstrate additional value. External validation: At a median follow-up of 23 months, higher MIC-1/GDF15 levels at BL and preC3 predicted shorter OS (BL; HR 1.4 95%CI 1.2-1.6; p < 0.0001 and preC3; HR 1.6 95%CI 1.3-1.8; p < 0.0001). Higher pre C3 MIC-1/GDF15 levels were also associated with shorter time to PSA progression (HR 1.2 95% CI 1.0-1.4; p = 0.02). Rise in MIC-1/GDF15 from BL to preC3 correlated with lack of 50% PSA fall at 12 weeks (p < 0.001). Conclusions: Adherence to a biomarker development pipeline provides level 2 evidence of the prognostic value of circulating MIC-1/GDF15 in men with mCRPC receiving docetaxel. A prospective biomarker led study is now necessary to establish clinical utility.

Phase II study of pembrolizumab in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC): Updated follow-up of cohorts (C) one to three from KEYNOTE-199.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17584-e17584
Author(s):  
Jeffrey C. Goh ◽  
Jose Maria M. Piulats Rodriguez ◽  
Marine Gross-Goupil ◽  
Ulka N. Vaishampayan ◽  
Ronald De Wit ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Phase 2 Study ◽  
Psa Response ◽  
Psa Progression ◽  
Pretreated Patients ◽  
Previously Treated ◽  
Grade 3

e17584 Background: Pembrolizumab monotherapy has shown antitumor activity and acceptable safety in patients with mCRPC previously treated with a next-generation hormone agent (NHA) and docetaxel. Presented herein are updated results from KEYNOTE-199 (NCT02787005), a multicohort phase 2 study, in patients with RECIST-measurable PD-L1+ disease (C1), RECIST-measurable, PD-L1− disease (C2), and bone-predominant disease, irrespective of PD-L1 (C3). Methods: Patients who previously received ≥1 NHA and 1 or 2 chemotherapies, including docetaxel, received pembrolizumab 200 mg Q3W for 35 cycles or until progression/toxicity. The primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Key secondary end points were DCR, PSA response rate (≥50% decrease from baseline), time to PSA progression, rPFS, OS, DOR, and safety. rPFS and OS were evaluated using the Kaplan-Meier method. Results: Of 258 treated patients (C1, 133; C2, 67; C3, 58), 6 completed therapy (C1, 4; C3, 2) and 252 discontinued (C1, 129; C2, 67; C3, 56), primarily due to progression (C1, 106; C2, 61; C3, 45). Median (range) time from enrollment to data cutoff was 31.3 mo (26.7-34.7) in C1, 30.6 mo (28.0-34.1) in C2, and 32.6 mo (27.4-34.4) in C3. Efficacy results are displayed in the table. ORR (95% CI) for patients with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2. Of 10 responders, 6 had a DOR ≥18 mo. Median time to PSA progression was 4 mo across cohorts. Any grade treatment-related AEs (TRAEs) occurred in 57-60% of patients across C1-3. Grade ≥3 TRAEs occurred in 16% of patients in C1, 15% in C2, and 17% in C3; 1 patient in each cohort died of a TRAE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: Pembrolizumab monotherapy was well tolerated and showed durable, antitumor activity and disease control with survival up to 24 mo in 3 cohorts of docetaxel and NHA-pretreated patients with RECIST-measurable or bone-predominant mCRPC. Clinical trial information: NCT02787005 . [Table: see text]

Overcoming chemotherapy resistance in patients (pts) with chemotherapy-failure, castration-resistant prostate cancer (CRPC) with sorafenib.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 127-127 ◽  
Author(s):  
Chadi Nabhan ◽  
Peter Hubert Cygan ◽  
Andrew Meyer ◽  
Kathy Tolzien ◽  
Angel G. Galvez ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Chemotherapy Resistance ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Chemotherapy Agent ◽  
Castration Resistant ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Number Of Treatment

127 Background: SOR is an oral multi kinase inhibitor that promotes apoptosis through downstream pathways that can be deregulated in CRPC leading to chemotherapy resistance. We hypothesized that SOR Could overcome chemotherapy resistance in non-responders or in those who progress shortly after stopping chemotherapy. Methods: Eligible pts were those who progressed while receiving chemotherapy [docetaxel (D) or mitoxantrone (M)] or within 12 weeks from stopping it. Pts were then continued or resumed on their last chemotherapy with the addition of SOR at 400 mg PO BID. Pts were allowed a maximum of 6 cycles of chemotherapy +SOR followed by SOR as monotherapy until progression. Primary end point: Safety of SOR+ chemotherapy. Secondary end points: Toxicity, time to progression (TTP). And responses (biochemical and radiographic) Results: Twenty-two pts were enrolled; 21 evaluable (73% Gleason ≥ 7). Median age was 68 (59-83). Median PSA was 142 ng/dl (13.6-9,584). Median time from last chemotherapy to SOR was 4 weeks. Visceral and bone disease was present in 64%. D was given in 16 pts while M in 6. Ten pts (45%) showed biochemical response (18% with >50% PSA decline). Despite progression before being on study, 16 pts (76%) achieved SD after starting SOR for a median duration of 6 months (4-12). The combination of SOR with either chemotherapy agent proved safe. Main grade 3/4 non-hematologic toxicities: Fatigue 7 (32%), 4 (18%) hand/foot syndrome, hypocalcemia and hyperglycemia in 2 pts (9%) each. Grade 3/4 leukopenia was seen in 7 (31%), neutropenia in 6 (27%), and thrombocytopenia in 2 (9%). Dose reduction of SOR occurred at least once in 15 pts (68%). Major reasons are hand/foot syndrome (22%), fatigue (22%), rash (13%), and neutropenia (9%). With a median follow-up of 19 months (3-46), 5 pts (23%) remain alive for a median OS of 8 months. TTP by PSA was 3 months (2-6) and TTP by imaging and/or clinically was 6 months (2-12). Median number of treatment cycles given was 6 (1-10). Conclusions: SOR can safely be combined with chemotherapy. SOR overcomes chemotherapy-resistance and shows biochemical and radiographic stability in this refractory pt population.

scholarly journals A Multicentric, Retrospective Efficacy and Safety Study of Nanosomal Docetaxel Lipid Suspension in Metastatic Castration-Resistant Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Aseem Samar ◽  
Srikant Tiwari ◽  
Sundaram Subramanian ◽  
Nisarg Joshi ◽  
Jaykumar Sejpal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Weekly Group

Purpose. To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods. In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m2) or 3-weekly regimens (75 mg/m2). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated. Results. Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5–25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9–15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns. Conclusions. Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.

A phase II study of sunitinib (SU) for maintenance therapy in metastatic castration-resistant prostate cancer (mCRPC) after response to docetaxel (D).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 151-151 ◽  
Author(s):  
B. J. Eigl ◽  
M. G. Trudeau ◽  
E. Winquist ◽  
K. N. Chi ◽  
M. Eliasziw ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Castration Resistant ◽  
Hand Foot Syndrome ◽  
Psa Response ◽  
Psa Progression ◽  
The Mean ◽  
Grade 3

151 Background: After treatment with D based chemotherapy, there is currently no standard therapy although new options are emerging. Due to its mechanism of action, acceptable toxicity profile and simple administration, SU has potential for therapeutic activity in the setting of maintenance therapy for patients with mCRPC who have responded to D based chemotherapy. Methods: Patients with mCRPC who had evidence of responding or stable disease at completion of D treatment were enrolled in this phase II multicentre trial. Patients received 50mg of SU daily on 4 week on/2 week off cycles. The primary endpoint was effect of SU maintenance on PFS. Because of potential effects of SU on PSA kinetics, clinical progression was defined independent of PSA. PSA response rate was a secondary endpoint. PSA-progression (PSA-P) was defined as a 25% PSA increase over baseline. Results: Thirteen patients have been enrolled and treated to date. Mean age was 63 years (47-76). ECOG scores of 0, 1, and 2 were reported for 4, 8 and 1 patients respectively. Mean number of prior cycles of D given was 9.5. A total of 28 cycles of SU were administered. A total of 291 adverse events (AEs) were recorded, of which 66%, 27%, and 7% were classified as Grades 1, 2, and 3, respectively. No Grade 4 AEs were seen. AEs were of a type and severity expected for SU. The most frequent grade 3 AEs were fatigue (n=3) and hand foot syndrome (n=3). No PSA responses have been documented. Most patients had immediate PSA increases without evidence of clinical progression. The mean PSAs increased by 159%, 396%, and 853% in Cycles 1, 2, and 3, respectively, corresponding to p-values of 0.18, 0.03, and 0.01 when compared to the PSA-P threshold of 25%. The trial will continue to complete its planned accrual of 26 evaluable patients and updated results, along with PFS, will be presented at the meeting. Conclusions: SU is well tolerated as maintenance therapy after D in men with mCRPC, with a predictable side-effect profile. PSA values after treatment with SU may not reflect progression in patients with mCRPCas significant increases were observed as early as Cycle 2 without clinical evidence of worsening disease. [Table: see text]

KEYNOTE-365 cohort A updated results: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 100-100 ◽  
Author(s):  
Evan Y. Yu ◽  
Josep M. Piulats ◽  
Gwenaelle Gravis ◽  
Brigitte Laguerre ◽  
Jose Angel Arranz Arija ◽  
...  
Keyword(s):  
Castration Resistant Prostate Cancer ◽  
2Nd Generation ◽  
Castration Resistant ◽  
Psa Response ◽  
Pretreated Patients ◽  
Phase 1B ◽  
Grade 3 ◽  
Individual Profiles ◽  
Clinical Trial Information

100 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study evaluating pembro + other agents in mCRPC. Updated results from cohort A (pembro + olaparib) are reported. Methods: Docetaxel-pretreated, molecularly unselected pts with mCRPC with progression within 6 mo of screening per PSA or radiologic bone/soft tissue progression enrolled. Pts may have received 1 other chemotherapy and ≤2 2nd-generation hormone therapy (HT). Pts received pembro 200 mg IV Q3W + olaparib 400 mg PO BID. Primary end points: safety, PSA response rate (confirmed PSA decline ≥50%), and ORR per blinded independent central review. Results: Of 84 treated pts, 42 discontinued, primarily due to progression (n=29). Median age was 71 y (range, 47-83); 26% were PD-L1+, 26% had visceral disease, and 57% had RECIST-measurable disease. Median follow-up was 3 mo for all pts (n=81) and 14 mo for pts with ≥27 wks’ follow-up (n=41). See Table for efficacy outcomes. Treatment-related AEs occurred in 70 (83%) pts. Most frequent (≥30%) were nausea (33%) and anemia (31%). Grade 3-5 treatment-related AEs occurred in 29 (35%) pts. Three pts died of AEs (2 treatment related [l myocardial infarction, 1 unknown cause]). Conclusions: With additional follow-up, pembro + olaparib continued to show activity in docetaxel-pretreated, molecularly unselected pts who previously received HT for mCRPC. Safety of the combination was consistent with individual profiles of each agent. Clinical trial information: NCT02861573. [Table: see text]

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