Abstract
There is emerging evidence for the use of poly (ADP-ribose) polymerase inhibitors
(PARPi) in patients with mCRPC with patients harboring germline or somatic mutations
deriving clinical benefit. However, the toxicity profile of PARPi in mCRPC is not
well established. In March 2022 a literature search was conducted across 4 databases
– Medline, PubMed, Cochrane Library and Embase. In total, 14 relevant studies were
identified cumulating in 2066 patients that were treated with PARPi. The overall ORR
to PARPi alone or in combination with other therapy was 37% (246/666). In 5trials
that investigated PARPi alone, the ORR was 39% (141/361). Treatment emergent adverse
events (TEAEs) of any grade were reported in 96% (1034/1080) in PARPi treatment arms.
TEAEs of grade >= 3 were reported in 57% (611/1080). 45% (457/1006) experienced treatment
interruption whilst 31% (310/989) required dose reductions. 11% (114/1006) of patients
had their treatment discontinued directly as the result of toxicity associated with
the trial medications. The most common hematological toxicity was anemia, reported
in 490/1160 (42%) patients. and lowered white blood cell count were the next 2most
common toxicities, reported in 186/655 (28%) and 133/729 (18%) respectively. The 3most
common non-hematological toxicities reported were nausea, fatigue and anorexia reported
in 440/1013 (43%), 340/1013 (34%) and 274/1013 (27%) patients respectively. Overall,
TRAEs associated with individual PARPi are still emerging with hematological toxicities
being most apparent. Further toxicities will be informed from future clinical trials
to allow improved treatment selection, education and management of toxicities in prostate
cancer.
Keywords
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Article info
Publication history
Published online: July 14, 2022
Accepted:
July 9,
2022
Received in revised form:
July 7,
2022
Received:
April 23,
2022
Identification
Copyright
Crown Copyright © 2022 Published by Elsevier Inc. All rights reserved.
