Risk of fatigue and anemia in patients with advanced cancer treated with olaparib: A meta-analysis of randomized controlled trials

Ruiz-Schutz, V.C.; Gomes, L.; Mariano, Rodrigo; Almeida, Daniel Vargas Pivato de; Pimenta, Juliana Martins; Molin, Graziela Zibetti Dal; Kater, Fabio; Yamamura, Rosely; Neto, Nelson F. Correa; Maluf, Fernando C.; Schütz, Fábio Augusto Barros

doi:10.1016/j.critrevonc.2019.06.012

Cited by 37 publications

(30 citation statements)

References 34 publications

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“…A meta‐analysis of 12 RCTs showed that PARP inhibitors are commonly associated with hematologic toxicities 13 . In another meta‐analysis of nine olaparib trials (2074 patients with advanced ovarian, gastric, prostate, lung, or BC), 14 the relative risk of all‐grade and high‐grade anemia for olaparib (including combination treatments) versus placebo/control was 2.10 (95% confidence interval [CI]: 1.48–2.98) and 3.15 (95% CI: 1.73–5.71), respectively. The risk of anemia remained significant after excluding concomitant chemotherapy and olaparib dose <300 mg BID (twice daily) (or equivalent) 14 .…”

Section: Introductionmentioning

confidence: 99%

“…In another meta‐analysis of nine olaparib trials (2074 patients with advanced ovarian, gastric, prostate, lung, or BC), 14 the relative risk of all‐grade and high‐grade anemia for olaparib (including combination treatments) versus placebo/control was 2.10 (95% confidence interval [CI]: 1.48–2.98) and 3.15 (95% CI: 1.73–5.71), respectively. The risk of anemia remained significant after excluding concomitant chemotherapy and olaparib dose <300 mg BID (twice daily) (or equivalent) 14 . Although occurrences of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML) have previously been reported in patients taking olaparib, 15 olaparib did not increase the risk of MDS/AML versus placebo in SOLO2; instead, a trend of MDS/AML occurrences was seen against the number of prior lines of platinum therapy 16 .…”

Section: Introductionmentioning

confidence: 99%

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Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

Ngu

Tse

Chu

et al. 2021

Asia-Pac J Clncl Oncology

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AimFew real‐world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate‐ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real‐life settings and to explore dose modification strategies.MethodsWe conducted a detailed examination of the clinical records of OC patients who were treated with olaparib at the Gynecologic Oncology Unit in Hong Kong from September 2015 to December 2019, including baseline characteristics, treatment outcomes, AEs, and management strategies, particularly dose modifications.ResultsNineteen patients were included, with a median olaparib treatment duration of 12 (range: 3–30) months. For recurrent platinum‐sensitive cases (n = 16), the median progression‐free survival was 16.0 months (95% confidence interval: 9.5–22.5). Eighteen (95%) patients experienced AE(s) of any grade, including four (21%) who experienced grade ≥3 AE(s). The most common AEs were as follows: nonhematologic fatigue (68%), nausea (42%), vomiting (26%), decreased appetite (26%), dyspepsia (21%), dizziness (21%), anemia (37%), neutropenia (26%), and thrombocytopenia (21%). Four specific cases involving anemia, lower limb lymphedema, myeloid neoplasm, and erythema nodosum are discussed separately. Eight patients required dose interruption or reduction due to AEs, of which five patients attempted and tolerated dose re‐escalation.ConclusionIn this study, most AEs were mild, but rare AEs were observed. In OC patients, olaparib AE management with dose reductions followed by re‐escalations was feasible, including for anemia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

Ngu

Tse

Chu

et al. 2021

Asia-Pac J Clncl Oncology

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“…however, these findings are different from our results. Another previous meta-analysis 41 was performed for the risk of anaemia in patients treated with olaparib and demonstrated that olaparib had an association with a significantly increased risk of anaemia.…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested by the previous study that neutropenia was the most common severe haematologic toxicity, and olaparib and veliparib had no association with an increased risk of severe anaemia; however, these findings are different from our results. Another previous meta‐analysis 41 was performed for the risk of anaemia in patients treated with olaparib and demonstrated that olaparib had an association with a significantly increased risk of anaemia. Our meta‐analysis included 29 phase II and III RCTs about 5 PARP inhibitors, and cancer types other than ovarian cancer were included and analysed in the research.…”

Section: Discussionmentioning

confidence: 99%

Haematologic toxicities with PARP inhibitors in cancer patients: an up‑to‑date meta‑analysis of 29 randomized controlled trials

Wang

2021

J Clin Pharm Ther

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The family of Poly ADP-ribose polymerase (PARP) consists of 18 members, and they play a key role in the complex landscape of DNA repair mechanism. 1 PARP is a nuclear protein that is activated by breaks in DNA single strands, which then further recruits DNA repair proteins with synthesis of poly (ADP-ribose) chains. 2 PARP inhibitors were developed to specifically target the DNA repair pathways involved with PARP1, as well as the other PARP enzymes. PARP inhibitors have been utilized to improve and maintain the curative effect of chemotherapy

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“…AEs observed in placebo arms of randomized trials are potential sources and AE literature reviews have recently contributed to drug development (4). Interestingly, there was a high level of heterogeneity, and a correlation between AE frequencies in placebo groups and those in treatment arms (5).…”

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confidence: 99%

Headache Reporting in Oncology Trials Depends on the Demographics of the Study Population

Wolff

2021

In Vivo

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Background/Aim: The frequency of adverse events (AEs) in clinical trials without control arms is difficult to interpret. Materials and Methods: This is a systematic literature review of AEs reported from the placebo arms of randomized cancer trials in PubMed between 2008 and 2020. Results: We found 80 placebo patient cohorts in 73 publications, describing 17,968 subjects who received placebo. Headaches were reported in 35 patient cohorts with an average frequency of 12.3% (+/-SD=8.0, range=0.4-34.1), and were more common in cohorts with a median age between 45 and 50 years, with higher performance status, and breast cancer (average 29.8% +/-SD=6.1). AEs leading to discontinuation were reported in 5% of cohorts (+/-SD=5.1, range=0-22.7). Conclusion: Considering covariates allows more accurate interpretation of the observed AE frequencies in cancer trials.

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Risk of fatigue and anemia in patients with advanced cancer treated with olaparib: A meta-analysis of randomized controlled trials

Cited by 37 publications

References 34 publications

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

Haematologic toxicities with PARP inhibitors in cancer patients: an up‑to‑date meta‑analysis of 29 randomized controlled trials

Headache Reporting in Oncology Trials Depends on the Demographics of the Study Population

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