ArticlePDF Available

Olaparib-Induced Purpuric Drug Eruption in a Patient with Castration-Resistant Prostate Cancer

Authors:
Mana Sekine
Mana Sekine
Mana Sekine
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Hitoshi Terui
Hitoshi Terui
Hitoshi Terui
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Taku Fujimura at Tohoku University
Taku Fujimura
Yoshihide Asano
Yoshihide Asano
Yoshihide Asano
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Download full-text PDF
Read full-text
Download citation

Abstract

Olaparib is recently approved as an anti-tumor agent for several cancers, including castration-resistant prostate cancer, which inhibits poly (adenosine diphosphate-ribose) polymerase, a DNA repair factor. Since olaparib is a newly approved drug, there are few reports of skin disorders that may be triggered by olaparib administration. In this report, we present a case with an olaparib-induced drug eruption presenting multiple purpuras on the patient’s fingers and fingertips. The present case suggests that olaparib might induce purpura as nonallergic drug eruption.
Available via license: CC BY-NC 4.0
Content may be subject to copyright.
Case Reports
in Oncology
Case Rep Oncol 2023;16:419–421
DOI: 10.1159/000530981
Received: November 5, 2022
Accepted: May 3, 2023
Published online: June 2, 2023
© 2023 The Author(s).
Published by S. Karger AG, Basel
www.karger.com/cro
This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License
(CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial
purposes requires written permission.
Case Report
Olaparib-Induced Purpuric Drug
Eruption in a Patient with
Castration-Resistant Prostate Cancer
Mana Sekine Hitoshi Terui Taku Fujimura Yoshihide Asano
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
Keywords
Olaparib ·Purpura ·Drug eruption ·Drug reaction ·Castration-resistant prostate cancer
Abstract
Olaparib is recently approved as an anti-tumor agent for several cancers, including castration-
resistant prostate cancer, which inhibits poly (adenosine diphosphate-ribose) polymerase, a DNA
repair factor. Since olaparib is a newly approved drug, there are few reports of skin disorders that
may be triggered by olaparib administration. In this report, we present a case with an olaparib-
induced drug eruption presenting multiple purpuras on the patient’sfingers and fingertips. The
present case suggests that olaparib might induce purpura as nonallergic drug eruption.
© 2023 The Author(s).
Published by S. Karger AG, Basel
Introduction
Olaparib is recently approved as an anti-tumor agent for several cancers, including
castration-resistant prostate cancer, which inhibits poly (adenosine diphosphate-ribose)
polymerase, a DNA repair factor [1, 2]. Since olaparib is a newly approved drug, there are
few reports of skin disorders that may be triggered by olaparib administration. In this article,
we present a case with an olaparib-induced drug eruption presenting multiple purpuras on
the patient’sfingers and fingertips. The CARE Checklist has been completed by the authors for
this case report, attached as online supplementary material (for all online suppl. material, see
https://doi.org/10.1159/000530981).
Case Report
A 70-year-old male with a history of castration-resistant prostate cancer was referred to
our department with purpura on his fingers. He had been treated for diabetes mellitus for
Correspondence to:
Hitoshi Terui, hitoshiterui
@
derma.med.tohoku.ac.jp
4 years. He had prostate cancer with bone metastases and has been treated with radio-
therapies and chemotherapies with several regimens (intensity-modulated radiation therapy
with estramustine phosphate and leuprorelin, docetaxel, and cabazitaxel), but it recurred.
Since BRCA1 mutation was detected in tumor cells with FoundationOne
®
Liquid CDx, he was
administered olaparib (600 mg/day) for castration-resistant prostate cancer 2 months before.
A month after starting olaparib, he began experiencing painless, non-palpable purpura on his
fingertips, which gradually spread to other fingers. On his initial visit, he complained of
purpura and numbness on the fingertips without pain, and a physical examination revealed
disseminated, faint purpura primarily on the fingertips (Fig. 1a, b). There were no signs of
purpura in other body parts other than the fingers. A full blood count revealed a decrease in
white blood cell count (2,900/mL), hemoglobin (11.1 g/dL), and platelet count (123,000/
mL). He had a low platelet count 5 years prior, which was probably caused bybone metastasis.
Then, we administered topical moisturizer and tocopherol ointment, and when olaparib was
reduced to 300 mg/day, the purpura gradually disappeared and eventually resolved. Numb-
ness was also relieved in parallel with the skin improvement. Based on clinical presentation
and clinical course, our diagnosis was olaparib-induced purpuric drug eruption of the fingers
and fingertips. There were no signs of relapse after improvement.
Discussion
Olaparib is an anti-tumor agent that specifically inhibits poly (adenosine diphosphate-
ribose) polymerase [1, 2]. Olaparib has been permitted to be used for the treatment of several
cancer species by the Pharmaceuticals and Medical Devices Agency in Japan since 2020.
Olaparib is currently used for the treatment of castration-resistant prostate cancer, ovarian
cancer, inoperable or recurrent breast cancer, and unresectable pancreatic cancer. More than
30% of prostate cancers harbor deleterious aberrations in genes involved in repairing DNA
damage [1, 2]. BRCA1 and BRCA2 are well-characterized genes involved in homologous
recombination repair, and BRCA1 mutation was detected in the present case. Since olaparib is
a newly approved drug, case reports of olaparib-induced skin disorders are limited; only
erythema nodosum and cutaneous arteritis have been previously reported [3–5]. Notably,
these previous reports indicate that skin lesions mainly appear on the extremities [3–5]. In the
present case, we described a case of purpura limited to the fingers and fingertips after the
administration of olaparib monotherapy. Purpura due to thrombocytopenia and chilblains
ab
Fig. 1. Clinical images of purpura. a,bClinical manifestations of the patient at the initial visit. Non-
palpable purpura on his fingers and fingertips with no pain.
Case Reports
in Oncology
Case Rep Oncol 2023;16:419–421 420
DOI: 10.1159/000530981 © 2023 The Author(s). Published by S. Karger AG, Basel
www.karger.com/cro
Sekine et al.: Olaparib-Induced Purpuric Drug Eruption
might be a differential diagnosis, but, since his purpura immediately improved after reducing
the dose of olaparib, we concluded that this case was a nonallergic skin disorder caused by
olaparib. This report presents only a single case, but further cases may provide fundamental
insights into the mechanisms underlying olaparib-associated skin disorders. In the present
case, the purpura subsequently improved with reducing the dose of olaparib, which might be
considered for future cases with olaparib-induced drug eruption. Since the number of patients
treated with olaparib is expected to increase, and cutaneous symptoms will increase in the
future, dermatologists should keep in mind the possible skin disorders caused by olaparib.
Statement of Ethics
This article was conducted ethically in accordance with the Declaration of Helsinki. Ethics
approval was not required for this single case report in accordance with local/national guidelines.
The patient’s written informed consent to publish the case and clinical images was obtained.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
No funding was received for this case report.
Author Contributions
Mana Sekine, Hitoshi Terui, and Taku Fujimura treated the patient and acquired the
clinical data. Mana Sekine and Hitoshi Terui wrote the manuscript. Yoshihide Asano
supervised the study.
Data Availability Statement
All data generated or analyzed during this study are included in this article and its online
supplementary material. Further inquiries can be directed to the corresponding author.
References
1 de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate
cancer. N Engl J Med. 2020 May 28;382(22):2091–102.
2 Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Survival with olaparib in metastatic castration-
resistant prostate cancer. N Engl J Med. 2020 Dec 10;383(24):2345–57.
3 Wheelden M, Cream L, Sivik J, Robson M. A novel adverse event associated with olaparib therapy in a patient
with metastatic breast cancer. Case Rep Oncol Med. 2018;2018:9529821.
4 Iinuma S, Takahashi C, Negishi H, Ishida-Yamamoto A. Cutaneous arteritis during olaparib treatment for ovarian
cancer. J Dermatol. 2021 Mar;48(3):e140–1.
5 Gou R, Horikawa N, Kosaka K. Olaparib-induced cutaneous side effects in a patient with recurrent ovarian
cancer. BMJ Case Rep. 2022 Apr 20;15(4):e249177.
Case Reports
in Oncology
Case Rep Oncol 2023;16:419–421 421
DOI: 10.1159/000530981 © 2023 The Author(s). Published by S. Karger AG, Basel
www.karger.com/cro
Sekine et al.: Olaparib-Induced Purpuric Drug Eruption
ResearchGate has not been able to resolve any citations for this publication.
A Novel Adverse Event Associated with Olaparib Therapy in a Patient with Metastatic Breast Cancer
Article
Full-text available
  • Jun 2018
Olaparib was first FDA approved for use in women with advanced ovarian cancer and germline BRCA mutations. Based on the results of subsequent research, the use of this drug has been expanded to patients with metastatic breast cancer with germline BRCA mutation. With the use of a relatively new medication and a larger patient population eligible for therapy, monitoring for novel adverse events associated with therapy is important. This case represents a patient with metastatic breast cancer and germline BRCA2 mutation who developed erythema nodosum after initiation of therapy with olaparib capsules. Her characteristic rash appeared shortly after starting olaparib and recurred after restarting olaparib an additional two times. She was treated with short courses of prednisone therapy with or without holding olaparib with resolution of her rash. The patient was later restarted on olaparib capsules 200 mg twice daily, and she more recently has been maintained on olaparib tablets 300 mg twice daily. On both regimens, the patient experienced only attenuated episodes of erythema nodosum that have not required cessation of therapy or steroid therapy.
View
Olaparib-induced cutaneous side effects in a patient with recurrent ovarian cancer
Article
  • Apr 2022
Over the past decade, the treatment of ovarian cancer has been revolutionised by poly(ADP-ribose polymerase (PARP)) inhibitors. Based on the results from clinical trials, olaparib, a PARP inhibitor, is indicated for use in the first-line treatment for patients with BRCA gene mutations, and as a maintenance treatment in platinum-sensitive relapsed ovarian cancer after a complete or partial response to platinum-based chemotherapy. Although PARP inhibitors have been shown to be well tolerated, adverse side effects can affect the quality of life of patients and lead to the discontinuation of therapy. Here, we report a case of dermatosis of the left dorsal hand as a rare adverse side effect of olaparib. Dermatological adverse side effects may become the crux of a clinical problem that requires the cooperation of professionals in many fields.
View
View
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer
Article
  • Sep 2020
  • NEW ENGL J MED
Background: We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported. Methods: In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 ratio to receive olaparib (256 patients) or the physician's choice of enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A included 245 patients with at least one alteration in BRCA1, BRCA2, or ATM, and cohort B included 142 patients with at least one alteration in any of the other 12 prespecified genes. Crossover to olaparib was allowed after imaging-based disease progression for patients who met certain criteria. Overall survival in cohort A, a key secondary end point, was analyzed with the use of an alpha-controlled, stratified log-rank test at a data maturity of approximately 60%. The primary and other key secondary end points were reported previously. Results: The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population. Conclusions: Among men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in BRCA1, BRCA2, or ATM and whose disease had progressed during previous treatment with a next-generation hormonal agent, those who were initially assigned to receive olaparib had a significantly longer duration of overall survival than those who were assigned to receive enzalutamide or abiraterone plus prednisone as the control therapy, despite substantial crossover from control therapy to olaparib. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
View
Olaparib for Metastatic Castration-Resistant Prostate Cancer
Article
  • Apr 2020
Background Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition in patients with prostate and other cancers. Methods We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician’s choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review. Results In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib. Conclusions In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.)
View