Risk of pneumonitis in cancer patients treated with PARP inhibitors: A meta-analysis of randomized controlled trials and a pharmacovigilance study of the FAERS database

Ma, Zhuo; Sun, Xiaoying; Zhao, Zhixia; Lu, Wenchao; Guo, Qixiang; Wang, Shi-hao; You, Jiwen; Zhang, Yuhui; Liu, Lihong

doi:10.1016/j.ygyno.2021.05.012

Cited by 29 publications

(23 citation statements)

References 46 publications

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“… 28 A meta-analysis has also reported that PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI1.31–5.47], p=0.007) compared with control arms, and the fatality rate of pneumonitis was up to 16%. 29 Interstitial lung disease, pleural effusion, pulmonary mass and Pneumocystis jirovecii pneumonia were new and significant serious AEs of olaparib validated in our analysis. Interstitial lung disease, in particular, has the highest number of reported cases (107) and showed a high correlation with significant signal strength being ROR 7.92 (6.54–9.59), PRR 7.80 (6.46–9.42), IC 2.96 (2.57) and EBGM 7.76 (6.41), respectively.…”

Section: Discussionmentioning

confidence: 51%

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: Discussionmentioning

confidence: 51%

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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“…anti-epidermal growth factor receptor agents, anti-BRAF agents, cyclin-dependent kinase 4/6 inhibitors, poly (ADP-ribose) polymerase inhibitors, etc., with variable incidence] and immune checkpoint inhibitors (ICIs; 1%-4%). 4 , 11 , 12 , 13 , 14 Case-fatality rates vary between 0% and 51.3% according to different drugs. 4 …”

Section: Epidemiologymentioning

confidence: 99%

Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment

et al. 2022

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“…Low grade cough and dyspnea have been registered in 11–19% of those treated with PARP inhibitors in randomized phase III trials, while data are still scarce for ATR, CHK1 and WEE inhibitor monotherapy ( Table 2 ). In randomized controlled trials, the incidence of pneumonitis was below 1% with olaparib and niraparib, but a recent meta-analysis showed a significantly increased risk of this AE among patients treated with PARP inhibitors [ 25 , 26 , 62 ]. The same authors consulted the Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate pneumonitis incidence in the real-world setting and reported that an increasing number of events have been described from 2015 to 2019.…”

Section: Safety Profile Of Ddr-targeting Agentsmentioning

confidence: 99%

“…The same authors consulted the Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate pneumonitis incidence in the real-world setting and reported that an increasing number of events have been described from 2015 to 2019. These AEs generally occurred within 6 months from PARP inhibitor initiation and could present with a wide range of symptoms, from dyspnea to respiratory failure [ 62 ]. According to the prescribing information, patients with new or worsening respiratory symptoms as well as radiological abnormalities should interrupt olaparib and undergo proper diagnostic work-up.…”

Section: Safety Profile Of Ddr-targeting Agentsmentioning

confidence: 99%

Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents

Martorana

Silva

Sessa

et al. 2022

Cancers

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Targeting the inherent vulnerability of cancer cells with an impaired DNA Damage Repair (DDR) machinery, Poly-ADP-Ribose-Polymerase (PARP) inhibitors have yielded significant results in several tumor types, eventually entering clinical practice for the treatment of ovarian, breast, pancreatic and prostate cancer. More recently, inhibitors of other key components of DNA repair, such as ATR, CHK1 and WEE1, have been developed and are currently under investigation in clinical trials. The inhibition of DDR inevitably induces on-target and off-target adverse events. Hematological and gastrointestinal toxicities as well as fatigue are common with all DDR-targeting agents, while other adverse events are drug specific, such as hypertension with niraparib and transaminase elevation with rucaparib. Cases of pneumonitis and secondary hematological malignancies have been reported with PARP inhibitors and, despite being overly rare, they deserve particular attention due to their severity. Safety also represents a crucial issue for the development of combination regimens incorporating DDR-targeting agents with other treatments, such as chemotherapy, anti-angiogenics or immunotherapy. As such, overlapping and cumulative toxicities should be considered, especially when more than two classes of drugs are combined. Here, we review the safety profile of DDR-targeting agents when used as single agents or in combination and we provide principles of toxicity management.

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Risk of pneumonitis in cancer patients treated with PARP inhibitors: A meta-analysis of randomized controlled trials and a pharmacovigilance study of the FAERS database

Cited by 29 publications

References 46 publications

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

Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment

Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents

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