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  • 1
    Online Resource
    Online Resource
    Harborside Press, LLC ; 2021
    In:  Journal of the National Comprehensive Cancer Network Vol. 19, No. 3.5 ( 2021-03-20), p. EPR21-034-
    In: Journal of the National Comprehensive Cancer Network, Harborside Press, LLC, Vol. 19, No. 3.5 ( 2021-03-20), p. EPR21-034-
    Type of Medium: Online Resource
    ISSN: 1540-1405 , 1540-1413
    Language: Unknown
    Publisher: Harborside Press, LLC
    Publication Date: 2021
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  • 2
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 21 ( 2021-09), p. S245-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2540998-0
    detail.hit.zdb_id: 2193618-3
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  • 3
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 5198-5200
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Thoracic Oncology, Elsevier BV, Vol. 18, No. 6 ( 2023-06), p. 755-768
    Type of Medium: Online Resource
    ISSN: 1556-0864
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2223437-8
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  • 6
    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
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2023829-0
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4565-4565
    Abstract: Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin's lymphoma (NHL), encompassing 30-58% of all NHL cases and approximately 60,000 cases annually in the United States of America (US) alone (Tilly et al, 2015; Zolkefli, 2017). The treatment (tx) landscape for DLBCL has significantly expanded, with novel targeted therapies, immunotherapies in addition to chemotherapy and chimeric antigen receptor therapy (CAR-T) (Bachanova et al, 2020). The importance of shared decision-making in cancer tx selection is well recognized; yet, we lack data on patient preferences regarding DLBCL tx, and existing research on tx factors in other disease areas, such as regimen intensity, has shown mixed results (Van Hoogdalem et al, 2019; Rummel et al, 2017; Rubin and Peyrot, 1999).Thus, we aimed to examine patient preferences of tx characteristics across the DLBCL landscape. Methods: Data were drawn from the Adelphi DLBCL Disease Specific Programme™, a point-in-time survey of hematologists, hemato-oncologists, oncologists, and their DLBCL patients conducted in France (FR), Germany (DE), Italy (IT), Spain (SP), the United Kingdom and the US between Jan-May 2021. Eligible patients were asked by their consulting physician to voluntarily complete a patient self-completion form (PSC) capturing demographics and preferences encompassing their DLBCL tx options. Patient tx preference questions were presented in a simplified manner to reduce the risk of misinterpretation. Patients' level of acceptance for characteristics of tx options, such as the patients' willingness to "be hospitalized" or "wait longer" for a more effective tx, were rated using a 7-point Likert scale (1=total disagreement; 7=total agreement). A Likert score of 6-7 was considered "agreement", whilst a Likert score of 1-2 was considered "disagreement". Results: Data analysis were conducted on 441 DLBCL patients (FR: n=80, DE: n=150, IT: n=54, SP: n=43, UK: n=34, US: n=80) who completed a PSC (Table 1). At data collection, mean (standard deviation) age was 64.6 (12.4) years, 36% of patients were female, 19% working full- or part-time and 81% were on second line or later. 8%, 24%, 28% and 40% were at Ann Arbor disease stage I, II, III and IV respectively at the time of data collection. Overall, 43% of patients agreed that they would be willing to wait longer (up to 4 weeks) for a more effective tx (e.g. CAR-T) than a tx with no delays (not have to wait 4 weeks), whilst 41% of patients agreed that they would be willing to wait longer (up to 4 weeks) for a tx (e.g. CAR-T) if they were less likely to suffer side effects (SEs) than a tx with no delays. 32% and 31% of patients agreed that they would find being hospitalized (for a period of 1-2 weeks) for safety monitoring at the start (first 1-2 months) of their tx acceptable if they did not have to wait longer to start tx (up to 4 weeks) or if they were less likely to suffer SEs respectively. Finally, 37% of patients agreed that they would find being hospitalized (for a period of 1-2 weeks) for safety monitoring acceptable provided the tx was more effective (Table 1). Conversely, 9% of patients disagreed with the statement "I would find taking a continuous tx as an outpatient for my lymphoma acceptable". 20% of patients disagreed with the statement "I would find being hospitalized for monitoring (for a period of 1-2 weeks) at the start (first 1-2 months) of my tx acceptable if it were more effective". 17% of patients disagreed with the statement "I would find being hospitalized for monitoring (for a period of 1-2 weeks) at the start of my tx acceptable if it had less SEs". 9% of patients disagreed with the statement "I would be willing to wait longer (up to 4 weeks) for a tx (e.g. CAR-T) that was more effective than a tx with no delays" and 11% of patients disagreed with the statement "I would be willing to wait longer (up to 4 weeks) for a tx (e.g. CAR-T) if I were less likely to suffer SEs than a tx with no delays". Finally, 13% of patients disagreed with the statement "I would find being hospitalized (for a period of 1-2 weeks) for monitoring at the start (first 1-2 months) of my tx acceptable if I did not have to wait longer (up to 4 weeks) to start my tx" (Table 1). Conclusion: A substantial proportion of patients reported that the requirement to wait longer and need for hospitalization were of low concern for their tx selection, often reporting in favor of extended hospitalization if better tx efficacy and SE profile could be achieved. Figure 1 Figure 1. Disclosures Quek: Regeneron Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Ma: Regeneron Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8065-8067
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4111-4111
    Abstract: Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma (NHL) constituting 30-58% of all NHL (Tilly et al, 2015; Thieblemont et al, 2020). Treatment can include intensive multiagent chemotherapy and other novel therapies which carries risk for toxicities. Despite this, we lack data comprehensively depicting the quality of life of real-world patients with DLBCL, particularly in the modern era with novel therapies. Therefore, we aimed to compare Quality of Life (QoL) to reference populations and assess real-world DLBCL patients across multiple countries and lines of therapy. Methods: Real-world data were drawn from the Adelphi DLBCL Disease Specific Programme™ (DSP), a point-in-time survey of hematologists, hemato-oncologists, oncologists and their patients with DLBCL conducted in France (FR), Germany (DE), Italy (IT), Spain (SP), the United Kingdom (UK) and the United States of America (US) between Jan-May 2021. Patients were asked to voluntarily complete a patient self-completion form (PSC) capturing demographics and QoL data through the use of patient-reported outcome instruments: the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30), EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L), EQ-5D-5L Visual Analogue Scale and Work Productivity and Activity Impairment questionnaire. Bivariate analysis was conducted to compare all cancer and NHL-specific reference values from the EORTC QLQ-C30 manual (Scott et al, 2008) to DLBCL DSP data, and to review QoL across lines of therapy, defined as first line and second line (1L+2L) and third line and above (3L+). Statistical significance level was set at p & lt;.05. If functional scores were lower, when compared to reference values, within the DSP, this was indicative of a worse QoL in patients with DLBCL. For symptomatic scores the opposite was true; should the DSP value be higher, this was indicative of a worse QoL in patients with DLBCL. Results: Data analysis was conducted on 441 patients with DLBCL who completed a PSC (FR: n=80, DE: n=150, IT: n=54, SP: n=43, UK: n=34, US: n=80); at data collection, mean (standard deviation) age was 64.6 (12.39) years, 36% of patients were female, 19% working full- or part-time and 80% were relapsed/refractory, 29% were 3L+. 8%, 24%, 28% and 40% were at Ann Arbor disease stage I, II, III and IV respectively at the time of data collection. When comparing DLBCL DSP values to EORTC QLQ-C30 all cancer reference values for functional scores (Table 1), global health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning were significantly worse than all cancer reference values. In terms of symptoms, DSP values for fatigue, nausea and vomiting, dyspnea, appetite loss and diarrhea were significantly worse than all cancer reference values (Table 2). Results were mixed when comparing with EORTC QLQ-C30 NHL-specific reference values (Table 1) for functional scores; global health status was significantly worse for the DLBCL DSP population, whilst role functioning, cognitive functioning and social functioning were significantly better than NHL reference values. Significantly worse symptom scores were observed in the DLBCL DSP population (Table 2) for nausea and vomiting, pain, dyspnea and diarrhea when compared with the reference values. Functioning scores were significantly worse in 3L+ patients vs 1L+2L for global health status, physical functioning, role functioning, cognitive functioning and social functioning (Table 3). Fatigue, dyspnea and diarrhea symptomatic scores were significantly worse in 3L+ vs 1L+2L patients. Symptom burden was high across all lines of therapy (Table 4). Conclusion: Real-world patients with DLBCL demonstrated significantly worse QoL when compared with a general cancer reference population with respect to all functional scores, as well as fatigue, nausea and vomiting, dyspnea, appetite loss and diarrhea, underscoring the high symptom burden experienced by patients with DLBCL. Patients with DLBCL on 3L+ had significantly worse QoL than those on earlier lines of therapy with respect to global health status, physical functioning, role functioning, cognitive functioning and social functioning, fatigue, dyspnea and diarrhea indicating an unmet need in novel treatment options to help improve QoL in later lines. Figure 1 Figure 1. Disclosures Ma: Regeneron Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Quek: Regeneron Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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