New Medicines for Serious Diseases: The Case of the FDA’s Breakthrough Designation

2020 ◽  
Author(s):  
Manuel Hermosilla
Keyword(s):  
Breakthrough Designation

Niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Correlative measures of tumor response in phase II GALAHAD study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 118-118 ◽  
Author(s):  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Shahneen Kaur Sandhu ◽  
William Kevin Kelly ◽  
Eleni Efstathiou ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Duration Of Treatment ◽  
Brca Mutations ◽  
Repair Gene ◽  
Recist 1.1 ◽  
Dna Repair Gene ◽  
Breakthrough Designation

118 Background: Niraparib, a highly potent and selective poly (ADP-ribose) polymerase inhibitor (PARPi) received breakthrough designation by US FDA for treatment of pts with BRCA1,2 mutant mCRPC who progressed on taxane and androgen receptor-targeted therapy. Circulating tumor cells (CTC) detection associates with poor outcomes, with declining counts consistent with improved survival [1,2]. Methods: GALAHAD study assessed niraparib (300 mg daily) in pts with mCRPC+DRD (NCT02854436). Patients with non-measurable soft tissue disease by RECIST 1.1 were required to have a baseline CTC count ≥1 cell/7.5 mL blood. CTC response was defined as CTC conversion to <5 for pts with baseline CTC≥5 and CTC drop to 0 post-baseline for pts with ≥1 baseline CTC. Alkaline phosphatase (ALP) was collected at each monthly cycle. Results: For primary efficacy population of pts with BRCA1/2 mutations, the objective response rate (ORR) by RECIST 1.1 criteria was 41.4%. CTC response rates for this population were as high as ORR regardless of measurability (Table). Time to CTC response for each CTC responder will be shown. Radiographic progression-free survival (rPFS) durations were similar for patients with a measurable disease response and patients with CTC conversion. Median duration of treatment for responders of any type was 6.7mo (range: 2–27). DRD status, both BRCA and non- BRCA, for each responder will also be discussed. Trends in disease burden and markers of bone metabolism will also be quantitatively explored including 24% pts who were on treatment for at least one cycle who had ≥25% decreased unfractionated ALP from baseline. Conclusions: Niraparib showed clinical activity with CTC response and decline in ALP levels in mCRPC pts having biallelic BRCA mutations, which further supports its recent breakthrough designation. Clinical trial information: NCT02854436. [Table: see text]

scholarly journals PNS276 DOES FDA BREAKTHROUGH DESIGNATION AFFECT HTA RECOMMENDATIONS IN TERMS OF TIMING AND OUTCOME?

2019 ◽  
Vol 22 ◽  
pp. S809
Author(s):  
J. Cai ◽  
T. Wang ◽  
N. McAuslane ◽  
L. Liberti
Keyword(s):  
Breakthrough Designation
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