28 februari 2021: Op ASCO GU 2021 is een nieuwe studie met Talazoparib (Talzenna) bij patiënten met uitgezaaide prostaatkanker gepresenteerd. De resultaten van de nieuwe studie bevestigen de hoopvolle resultaten van eerder gepubliceerde resultaten. 

Zie dit studieprotocol: A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

Onderaan dit artikel abstract, zie ook verder de informatie hieronder.

24 februari 2020: Bron: Cancer research

Talazoparib (Talzenna) is een relatief nieuw medicijn en is een gerichte therapie specifiek gericht op vormen van kanker met DNA mutaties. Dit medicijn valt onder de PARP remmers - poly (ADP-ribose) polymerase (PARP) -remmer. De resultaten zijn veelbelovend vooral bij vormen van kanker waarbij deze mutaties ATMATRBRCA1BRCA2CHEK2FANCAMLH1MRE11ANBNPALB2, en RAD51C. een rol spelen. Zoals borstkanker, eierstokkanker, maar ook bij andere vormen van kanker zoals longkanker en prostaatkanker

In Cancer Research staat een overzicht van lopende studies met talazoparib , of alleen of in combinatie met andere medicijnen of vormen van immuuntherapie. De resultaten die nu al bekend zijn zijn veelbelovend. Belangrijk is ook dat de bijwerkingen van Talazoparib minder zijn dan andere vormen van behandelingen, al is het ook wel afhankelijk van stadium van kanker (tumorload) en lichamelijke gesteldheid van de kankerpatiënt. 

In het Europese trial register krijg ik op talazoparib deze search

In het Nederlandse trialregister krijg ik op talazoparib slechts 1 studie die loopt in het Erasmus Medisch Centrum: 

FUnctional selection of advanced breast cancer patients for Talazoparib treatment Using the REpair Capacity (RECAP) test:The FUTURE trial

Een anddere interessante studie uit 2017: Phase I, Dose-Escalation, Two-Part Trial of

the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers laat hoopvolle resultaten zien bij verschillende vormen van kanker met solide tumoren met specifieke DNA mutaties:

Aanhoudende PARP-remming werd waargenomen bij doses ≥0,60 mg / dag. Bij 1,0 mg / dag werden bevestigde responsen waargenomen bij 7 van de 14 (50%) en 5 van de 12 (42%) patiënten met BRCA-mutatie - geassocieerde borstkanker en eierstokkanker en bij patiënten met alvleesklierkanker en kleincellige longkanker. Talazoparib vertoonde antitumoractiviteit met één middel en werd goed verdragen door patiënten bij de aanbevolen dosis van 1,0 mg / dag.

Afgelopen week werden ook de resultaten bekendgemaakt van een fase II studie TALAPRO-1 studie tijdens het Genitourinary Cancers Symposium 2020, van 13 - 15 februari 2020 bij prostaatkankerpatiënten met uitgezaaide prsotaatkanker: 

Talazoparib als monotherapie heeft bemoedigende antitumoractiviteit aangetoond bij met docetaxel voorbehandelde patiënten met uitgezaaide, hormoon resistente prostaatkanker, vooral die met BRCA1 / 2-mutaties, en werd over het algemeen goed verdragen.

Een recente studie: An Effective Epigenetic-PARP inhibitor Combination Therapy for Breast and Ovarian Cancers Independent of BRCA-mutations laat ook zien dat Talazoparib ook bij geen aantoonbare BRCA 1 en BRCA 2 samen met DNMTi guadecitabine toch een positief effect kan hebben.

Hier enkele studies uit de lijst van Cancer Research, klik op de titel voor volledige beschrijving:

Combination Treatment (Talazoparib plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer with STK11 Gene Mutation (A LUNG-MAP Treatment Trial)

This phase II LUNG-MAP treatment trial studies how well combination treatment (talazoparib plus avelumab) works in treating patients with non-squamous non-small cell lung cancer that has an STK11 gene mutation and has come back (recurrent) or is stage IV.

Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors

Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration resistant prostate cancer (CRPC).

Talazoparib For Neoadjuvant Treatment Of Germline BRCA1 / 2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer

A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1 / 2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER

A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and / or abiraterone acetate / prednisone).
Location: 5 locations

Avelumab and Talazoparib in Treating Patients with MSS, MSI-H, and POLE-Mutated Recurrent or Persistent Endometrial Cancer

This phase II trial studies how well avelumab and talazoparib work in treating patients with microsatellite stable (MSS), high frequency microsatellite instability (MSI-H), and polymerase e (POLE)-mutated endometrial cancer that has spread to other places in the body or that does not go to remission despite treatment

A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors

This Phase 1b / 2 study will examine the effects of the study drugs, avelumab, binimetinib and talazoparib when given in a 2 (doublet) or 3 (triplet) drug combination, in patients with locally advanced or metastatic RAS-mutant solid tumors. The Phase 1b part of the study will assess if the different study drugs can be given together safely and which doses to use for further research. Phase 2 will test if the study treatments have an effect on tumor size and growth, and gather more information about potential side effects.

Zie voor meer studies met talazoparib op Cancer Research

A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer


For the multinational phase II TALAPRO-1 trial, 128 patients with progressive metastatic castration-resistant prostate cancer were enrolled between June 4, 2017 and March 20, 2020. All had at least a monoallelic DDR gene deleterious alteration likely to sensitize them to PARP inhibition identified from an 11-gene panel (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, and RAD51C). Positive DDR gene alteration status was defined as detection of homozygous deletions, putative deleterious genomic alterations, or a combination, in at least one gene. The patients had previously received one to two taxane-based chemotherapy regimens and at least one hormonal therapy with enzalutamide and/or abiraterone acetate given in the metastatic setting.

The patients received 1 mg oral talazoparib daily, or 0.75 mg daily if moderate renal impairment was present, until radiographic progression, unacceptable toxicity, consent withdrawal, or death. Radiographic assessments were performed every 8 weeks during the first 24 weeks, then every 12 weeks thereafter.

The primary endpoint was confirmed objective response rate (ORR) by blinded independent central review, while key secondary endpoints included time to objective response, response duration, radiographic progression-free survival (PFS), overall survival (OS), prostate-specific antigen (PSA) decrease of at least 50%, circulating tumor cell count conversion, and safety. Antitumor activity endpoints were analyzed by DDR groups, where patients were separated hierarchically by DDR gene alterations (BRCA1/2 > PALB2 > ATM > others). Dr. De Bono presented antitumor activity and tolerability results, with data cut-off on September 4, 2020.

The safety population (n = 127) included all patients who received at least one dose of talazoparib and a small number of patients with non-measurable disease who were enrolled in an earlier version of the protocol. The efficacy population (n = 104) included all patients with measurable soft tissue disease who had predefined tumor DDR gene alterations and had received at least one dose of talazoparib.

Baseline characteristics between both safety and efficacy populations were similar. Among all 127 patients, 48% had received more than one prior taxane-based regimen. Median duration of talazoparib treatment was 6.1 months in the safety population and 6.2 months in the efficacy population.

The ORR was 29.8% in the efficacy population (95% confidence interval 21.2–39.6). It was 45.6% for the BRCA2 alteration group, 50.0% for the BRCA1 group, 25.0% for the PALB2 group, and 11.8% for the ATM group. Reduction in tumor burden (79.8%), PSA (71.9%), and circulating tumor cell count (82.2%) was observed in most patients. These reductions were especially apparent in BRCA-altered cancers but were also found in PALB2- and ATM-altered cancers.

Time to objective response was 3.4 months (range 1.6–7.5 months), and median duration of response was 12.8 months in the efficacy population. The longest confirmed objective response was observed in patients with BRCA2 alterations. Twelve patients had an ongoing response at data cut-off. Median radiographic PFS was 5.6 months. It was 11.2 months for patients with BRCA1/2 alterations, 3.5 months for those with non-BRCA alterations, 5.6 months for those with PALB2 alterations, and 3.5 months for those with ATM alterations. Similar patterns were observed for OS and time to PSA progression.

The tolerability of talazoparib was consistent with previous reports. Of all 127 patients, 95.3% reported any all-causality treatment-emergent adverse events, the most common of which were anemia (48.8%), nausea (33.1%), decreased appetite (28.3%), and asthenia (23.6%). The most common grade 3/4 treatment-emergent adverse events were anemia (30.7%), thrombocytopenia (8.7%), and neutropenia (7.9%). Serious treatment-emergent adverse events were reported in 33.9%, which primarily included pulmonary embolism (6.3%), anemia (3.9%), disease progression (3.1%), urinary tract infection (2.4%), and pneumonia (2.4%). Permanent discontinuation of talazoparib due to treatment-emergent adverse events occurred in 11.8% of patients.

“Talazoparib monotherapy has important, substantial, and durable antitumor activity in DDR-mutated advanced metastatic castration-resistant prostate cancer in patients who have had prior taxane and novel hormonal therapy, most impressively in the BRCA-altered cancers, but also with antitumor activity in the PALB2- and ATM-altered cancers,” concluded Dr. De Bono.

The TALAPRO-1 trial was sponsored by Pfizer Inc.




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