Olaparib-Induced Severe Folate Deficiency in a Patient With Advanced Ovarian Cancer

Shammo, Jamile M.; Usha, Lydia; Richardson, Kristin; Elliott, Elizabeth J; Dewdney, Summer B.; Venugopal, Parameswaran; Cobleigh, Melody A.; Kuzel, Timothy M.

doi:10.1200/jop.18.00705

Cited by 9 publications

(11 citation statements)

References 1 publication

(2 reference statements)

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“…19 Several studies had also shown that the incidences of anemia, thrombocytopenia, neutropenia were about 50%, 30% and 25%, respectively. 3,20,21 In addition, significant AEs signal strengths of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) were presented in our analysis, which were corresponding to that in the instruction and clinical safety data. 22 Folate deficiency was reported as a new and significant AE of olaparib with signal strength being ROR 18.99 (8.48-42.54), ), IC 4.23 (1.00) and EBGM 18.72 (8.36), respectively, in our results.…”

Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 62%

“…A study has reported a severe folate deficiency case associated with olaparib therapy, which may explain anemia and other hematologic toxicities associated with the agent. 21 An advanced ovarian cancer patient was found to have an exceedingly low serum folate level (<1.6 ng/mL; normal range, 7–31.4 ng/mL) after taking olaparib, while the level of which was 14.0 ng/mL before initiation of olaparib. 21 It demonstrated that olaparib might cause folate deficiency with anemia.…”

Section: Discussionmentioning

confidence: 99%

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A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System

Shu¹,

He²,

Liu³

et al. 2022

CLEP

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Background: Olaparib, the world's first poly ADP-ribose polymerase (PARP) inhibitor (PARPi), has been approved for treatment of ovarian cancer, breast cancer, pancreatic cancer and prostate cancer by FDA. The current study was to assess olaparib-related adverse events (AEs) of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of olaparib-associated AEs. Results: Out of 8,450,009 reports collected from the FAERS database, 6402 reports of olaparib-associated AEs were identified. A total of 118 significant disproportionality preferred terms (PTs) conforming to the four algorithms simultaneously were retained. The most common AEs included anemia, thrombocytopenia, nausea, decreased appetite, blood creatinine increased and dermatomyositis, which were corresponding to those reported in the specification and clinical trials. Unexpected significant AEs as interstitial lung disease, Pneumocystis jirovecii pneumonia, folate deficiency, renal impairment and intestinal obstruction might also occur. The median onset time of olaparib-related AEs was 61 days (interquartile range [IQR] 14-182 days), and most of the cases occurred within the first 1 month after olaparib initiation. Conclusion: Results of our study were consistent with clinical observations, and we also found potential new and unexpected AEs signals for olaparib, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results could provide valuable evidence for further safety studies of olaparib.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System

Shu¹,

He²,

Liu³

et al. 2022

CLEP

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“…anemia, as severe folate deficiency contributing to anemia was observed in a small number of patients receiving olaparib in the relapsed disease setting; administering folate supplements ameliorated the requirement for transfusion and olaparib dose modification in one patient [14].…”

Section: Discussionmentioning

confidence: 99%

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial

Colombo

Moore

Scambia

et al. 2021

Gynecologic Oncology

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Detailed safety data from the SOLO1 trial of maintenance olaparib in newly diagnosed, advanced BRCA-mutated ovarian cancer.• Maintenance olaparib had a predictable tolerability profile with no new safety signals identified.• Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.• Risk of MDS/AML with maintenance olaparib in the newly diagnosed setting remained <1.5% with long-term follow-up of 5 years.• The majority of patients were able to remain on the recommended starting dose of olaparib 300 mg twice daily.

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“…Not only may patients and their close relatives become aware of being at increased risk of developing various cancer types, pathogenic BRCA1/2 variants are also treatment targets for poly ADP-ribose polymerase (PARP) inhibitors (33). Clinical complications related to anti-cancer treatment regimens (34)(35)(36) furthermore led to the development of genomic assays such as the 70-gene MammaPrint microarray with level 1A evidence of clinical utility for prediction of chemotherapy benefit (37). Microarray analysis using tumor samples reformed our past understanding of BC as a single disease to a complex disorder consisting of at least four major subtypes, namely luminal A, luminal B, HER2-enriched and basal-type.…”

Section: Discussionmentioning

confidence: 99%

Pioneering BRCA1/2 Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics

et al. 2021

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Research performed in South African (SA) breast, ovarian and prostate cancer patients resulted in the development of a rapid BRCA point-of-care (POC) assay designed as a time- and cost-effective alternative to laboratory-based technologies currently used for first-tier germline DNA testing. In this study the performance of the new assay was evaluated for use on a portable screening device (ParaDNA), with the long-term goal to enable rollout at POC as an inventive step to meet the World Health Organization’s sustainable development goals for Africa. DNA samples for germline testing were obtained retrospectively from 50 patients with early-stage hormone receptor-positive breast cancer referred for genomic tumor profiling (MammaPrint). Currently, SA patients with the luminal-type breast cancer are not routinely selected for BRCA1/2 testing as is the case for triple-negative disease. An initial evaluation involved the use of multiple control samples representing each of the pathogenic founder/recurrent variants included in the BRCA 1.0 POC Research Assay. Comparison with a validated laboratory-based first-tier real-time polymerase chain reaction (PCR) assay demonstrated 100% concordance. Clinical utility was evident in five patients with the founder BRCA2 c.7934delG variant, identified at the 10% (5/50) threshold considered cost-effective for BRCA1/2 testing. BRCA2 c.7934delG carrier status was associated with a significantly younger age (p=0.03) at diagnosis of breast cancer compared to non-carriers. In three of the BRCA2 c.7934delG carriers a high-risk MammaPrint 70-gene profile was noted, indicating a significantly increased risk for both secondary cancers and breast cancer recurrence. Initiating germline DNA testing at the POC for clinical interpretation early in the treatment planning process, will increase access to the most common pathogenic BRCA1/2 variants identified in SA and reduce loss to follow-up for timely gene-targeted risk reduction intervention. The ease of using cheek swabs/saliva in future for result generation within approximately one hour assay time, coupled with low cost and a high BRCA1/2 founder variant detection rate, will improve access to genomic medicine in Africa. Application of translational pharmacogenomics across ethnic groups, irrespective of age, family history, tumor subtype or recurrence risk profile, is imperative to sustainably implement preventative healthcare and improve clinical outcome in resource-constrained clinical settings.

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Olaparib-Induced Severe Folate Deficiency in a Patient With Advanced Ovarian Cancer

Abstract: Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 9 publications

References 1 publication

A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System

A Real-World Disproportionality Analysis of Olaparib: Data Mining of the Public Version of FDA Adverse Event Reporting System

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial

Pioneering BRCA1/2 Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics

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