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  • 1
    Online Resource
    Online Resource
    TALAPRO-2: a placebo-controlled phase III study of talazoparib (TALA) plus enzalutamide (ENZA) for patients with first-line metastatic castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS5598-TPS5598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS5598-TPS5598
    Abstract: TPS5598 Background: TALA blocks poly(ADP-ribose) polymerase (PARP) activity and traps PARP on single-strand DNA breaks, preventing DNA damage repair (DDR) and causing death of cells with DDR alterations (eg BRCA1/2). a TALA has been approved in multiple countries as monotherapy for germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative advanced breast cancer. ENZA is an androgen receptor (AR) inhibitor and an established therapy for mCRPC. As PARP activity has been shown to support AR function, inhibition of PARP is expected to reduce AR signaling and increase sensitivity to AR-directed therapies. In addition, AR blockade downregulates homologous recombination repair gene transcription which induces ‘ BRCAness ’. Therefore, combining TALA with ENZA in mCRPC may be efficacious regardless of DDR alterations. TALAPRO-2 (NCT03395197) is a Phase III, 2-part study to evaluate efficacy, safety, pharmacokinetics, and patient-reported outcomes (PROs) of TALA combined with ENZA. Methods: Enrollment goal is 1037 patients (19 patients, part 1 dose-finding; 1,018 patients, part 2 placebo-controlled). Key eligibility criteria: age ≥18 years; asymptomatic/mildly symptomatic mCRPC; ECOG performance status ≤1; metastatic disease (no brain metastases); and no prior life-prolonging systemic therapy for nonmetastatic CRPC or mCRPC. Prior therapies (excluding novel AR inhibitors) in the castration-sensitive (CSPC) setting are allowed. ADT must continue throughout the study. The randomized double-blind portion (part 2) will evaluate safety, efficacy, and PROs of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA (160 mg QD). Patients are stratified by prior novel hormonal therapy or docetaxel for CSPC (yes or no) and DDR alteration status (deficient vs nondeficient/unknown). The primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v.1.1 or in bone per PCWG3 criteria by independent review or death. The key secondary endpoint is overall survival. Efficacy will be assessed radiographically every 8 weeks up to Week 25 and every 8–12 weeks thereafter. rPFS will be compared between the two arms by a 1-sided stratified log-rank test. Patient recruitment is ongoing in multiple regions including US, Europe/Eastern Europe, Israel, South America, South Africa, and Asia-Pacific region. a DDR alterations are defined as known/likely pathogenic variants or homozygous deletions. Funding: Pfizer Inc. Clinical trial information: NCT03395197 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.TPS5598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Talazoparib in Patients with a Germline BRCA -Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial
    Oxford University Press (OUP) ; 2020
    In:  The Oncologist Vol. 25, No. 3 ( 2020-03-01), p. e439-e450
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 25, No. 3 ( 2020-03-01), p. e439-e450
    Abstract: In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. Materials and Methods Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time-varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient-reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. Results The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3–4 months of receiving talazoparib. Grade 3-4 anemia lasted approximately 7 days for both arms. Overlapping grade 3-4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low ( & lt;2%). A total of 150 (52.4%) patients receiving talazoparib had AEs associated with dose reduction. Hematologic toxicities were managed by supportive care medication (including transfusion) and dose modifications. Among patients with anemia or nausea and/or vomiting AEs, PROs favored talazoparib. After accounting for the treatment-emergent period, talazoparib was generally associated with a lower rate of hospitalization and supportive care medication use compared with chemotherapy. Conclusion Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1634/theoncologist.2019-0493
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2023829-0
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  • 3
    Online Resource
    Online Resource
    TALAPRO-2: A placebo-controlled phase III study of talazoparib (TALA) plus enzalutamide (ENZA) for patients with first-line metastatic castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. TPS264-TPS264
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. TPS264-TPS264
    Abstract: TPS264 Background: TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/2 and traps PARP on DNA, preventing DNA damage repair (DDR) and causing death of cells with DDR mutations (eg BRCA1/2). TALA is approved in multiple countries for germline BRCA1/2-mutated HER2- advanced breast cancer. ENZA is an established therapy for CRPC. PARP1 activity has been shown to support AR function, suggesting that co-blockade of PARP1 may synergize with AR-directed therapy, regardless of DDR deficiency. A combination of TALA with ENZA in mCRPC may improve clinical outcomes in patients with or without DDR-deficient tumors. TALAPRO-2 (NCT03395197) is a 2-part study to evaluate efficacy, safety, pharmacokinetics, and patient (pt)-reported outcomes (PROs) of the combination. Methods: Enrollment goal is 1037 pts (19 pts, part 1 dose-finding; 1,018 pts, part 2 placebo-controlled). Key eligibility criteria: age ≥18 y, asymptomatic/mildly symptomatic mCRPC, ECOG performance status ≤1, no brain metastases, and no prior life-prolonging systemic therapy in nonmetastatic CRPC or mCRPC state. Prior docetaxel or novel hormonal therapy (excluding novel AR inhibitors) in castration sensitive (CSPC) setting is allowed. The randomized double-blind portion will evaluate safety, efficacy, and PROs of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA (160 mg QD). Randomization is stratified by prior NHT or docetaxel for CSPC (yes/no) and DDR mutation status (deficient vs nondeficient/unknown). The primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v.1.1 or in bone per PCWG3 criteria or death. The key secondary endpoint is overall survival (OS). Efficacy will be assessed by radiography every 8 weeks up to week 25 and every 8–12 weeks thereafter. rPFS will be compared between two arms by a 1-sided stratified log-rank test. Pt recruitment is ongoing in multiple regions including US, Europe/Eastern Europe, Israel, South America, South Africa, and Asia Pacific region. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03395197.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.TPS264
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    TALAPRO-2: A two-part, placebo-controlled phase III study of talazoparib (TALA) with enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. TPS337-TPS337
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. TPS337-TPS337
    Abstract: TPS337 Background: ENZA is approved to treat men with CRPC. TALA is a poly(ADP-ribose) polymerase (PARP) inhibitor that inhibits PARP1/PARP2 and traps PARP on DNA, preventing DNA damage repair (DDR), and causing cell death in BRCA1/2-mutated cells. TALA is approved in the US to treat germline BRCA1/2-mutated HER2- locally advanced/metastatic breast cancer. A combination of TALA with ENZA in mCRPC may improve clinical outcomes. Methods: Eligible patients (pts) in parts (P) 1 and 2 of this study are aged ≥18 years; have asymptomatic/mildly symptomatic mCRPC, ECOG PS ≤1, and no brain metastases; and have not received taxanes/novel hormonal therapy (NHT). P1 is an open label study to confirm the starting dose of TALA to be given in combination with ENZA. P2 is a randomized double-blind study that will evaluate the safety, efficacy and pt reported outcomes of TALA (0.5 mg QD) + ENZA (160 mg QD) vs placebo + ENZA in 2 cohorts (C). C1: pts with mCRPC (all comers) (N = 560); C2: pts with DDR gene mutations likely to sensitize to PARP inhibition (DDR deficient) (N = 300). Randomization will be stratified by prior treatment with NHT for castration sensitive prostate cancer (CSPC) or prior treatment with taxane-based chemotherapy for CSPC (yes/no), and DDR mutation status (deficient vs. nondeficient/unknown). For P1, the primary endpoint is safety; the secondary endpoint is pharmacokinetics of TALA and ENZA. For P2, the primary endpoint is radiographic progression-free survival (rPFS), defined as time to progression in soft tissue per RECIST v1.1 or in bone per PCWG3 criteria or death and evaluated separately in all comers (C1) and DDR-deficient (DDR-deficient pts from C1 and C2 combined, N = 380 pts) populations. The key secondary endpoint is overall survival. Efficacy will be assessed by radiography every 8 weeks up to week 25 and every 8-12 weeks thereafter. P2 analysis for rPFS is powered at 90% and 85% using a 2-sided log-rank test with alpha of 0.025, respectively, in the all comers and DDR deficient populations. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03395197.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.TPS337
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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