Share this entry
Talazoparib in advanced breast cancer patients with a germline BRCA1/2 mutation
By: News Feed | Last updated: 19th August 2018 | In: Breast Cancer, Chemotherapy, Oncology, Targeted Therapies
BMN-673, breast cancer, capecitabine, eribulin, gemcitabine, Medivation, PARP, PARPi, Pfizer, talazoparib, vinorelbine
Single-agent PARP-inhibition with talazoparib is associated with an improved progression-free survival (PFS) and better patient-reported outcomes (PRO) when compared to chemotherapy alone in patients with advanced breast cancer (ABC) and a germline BRCA1/2 mutation, as reported by the investigators of the Phase III EMBRACA study (NCT01945775).
Cancer cells with deleterious mutations in breast cancer susceptibility genes 1 or 2 (BRCA1/2) are deficient in the repair mechanism for DNA double-strand breaks, leaving these tumours highly dependent on the repair pathway for single-strand breaks. This pathway is regulated by the enzyme poly(adenosine diphosphate–ribose) polymerase (PARP), wrote the authors in the New England Journal of Medicine.
The Phase III, open-label, EMBRACA study randomised 431 advanced breast cancer patients harbouring a germline BRCA1/2 mutation 2:1 to receive talazoparib or physician’s choice (PC) single-agent chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) in continuous 21-day cycles. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR).
The median PFS in the talazoparib group was 8.6 months vs 5.6 months in the chemotherapy group (hazard ratio [HR]=0.54; 95% CI, 0.41-0.71; p<0.001). At 57% of the projected events, the interim median HR for death measured 0.76 (95% CI, 0.55-1.06; p=0.11). Moreover, talazoparib was associated with a significantly higher objective response rate (ORR) when compared to PC chemotherapy; 62.6% vs. 27.2%, respectively (OR=5.0; 95% CI, 2.9-8.8; p<0.001).
PRO was assessed by means of the global health status-quality-of-life and breast symptoms scales. Both favoured talazoparib, patients reported a significant overall improvement and significant delay in the time to clinically meaningful deterioration.
Non-haematologic Grade 3 adverse events (AEs) occurred in 32% vs 38% of patients treated with talazoparib vs chemotherapy, respectively. Haematologic Grade 3-4 AEs, primarily anaemia, were reported in 55% (talazoparib group) and in 38% (chemotherapy group).
Litton JK, et al. N Engl J Med. 2018; doi: 10.1056/NEJMoa1802905.
Do you like our content? Subscribe to our non-intrusive newsletter today! We promise we won’t be spammy.
YOU MAY ALSO LIKE
This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
© Copyright 2018 MediPaper Medical Communications Ltd. – Talazoparib in advanced breast cancer patients with a germline BRCA1/2 mutation