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Olaparib monotherapy or combination therapy in lung cancer: an updated systematic review and meta- analysis
Sajjad Hajihosseini1, Ehsan Emami1, Seyed Amirali Zakavi2
1Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran.
Background And Aims:
Impaired double strand DNA repair by homologous repair deficiency (HRD) leads to sensitivity to poly ADP ribose polymerase (PARP) inhibition. A subset of non-small cell lung cancers (NSCLCs) harbour impaired DNA double strand break repair. This study aims to investigate meta-analysis on the olaparib monotherapy or combination therapy in lung cancer.
Methods:
A comprehensive search was conducted in Pubmed, Scopus and Google Scholar data bases up to August 13, 2023 related articles were extracted title, abstract and full text of articles were screened. The quality included articles were assessing the data was extracted and hence analysis.
Results:
After screening 5208 articles, 9 were selected for final review based on relevance to the topic. Olaparib monotherapy increased progression free survival (PFS) level [ES= 7.76; 95% CI= 0.16 to 1.36; P=0.208]. Olaparib maintenance therapy increased PFS compared to placebo in platinum-sensitive NSCLC patients [ES= 0.9; 95% CI= 0.9 to 0.9]. Combination therapy with durvalumab and olaparib decreased PFS level compared to the olaparib group [ES=6.07; 95% confidence interval (95% CI) = 0.67 to 11.46; P=0.000]. Adding gefitinib to olaparib decreased PFS compared to olaparib only group, significantly (ES=3.39; 95% CI=-0.78 to 7.56; P=0.609).
Conclusions:
Our study demonstrated olaparib as monotherapy can increase the PFS of patients with lung cancer, but the combination of olaparib and gefitinib or the combination of olaparib plus durvalumab couldn't have a significant effect. According to the high heterogeneous rate of studies further large-scale randomized control trials are still required to progress association.
Systematic Review Registration:
Open Science Framework (OSF).
Insights
Olaparib monotherapy shows promise in improving progression-free survival (PFS) for lung cancer patients. However, combining olaparib with gefitinib or durvalumab did not yield significant PFS benefits in this meta-analysis.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Homologous repair deficiency (HRD) impairs DNA double-strand break repair, leading to sensitivity to poly ADP ribose polymerase (PARP) inhibitors.
- A subset of non-small cell lung cancers (NSCLCs) exhibits impaired DNA repair mechanisms.
- PARP inhibitors, such as olaparib, are a targeted therapy approach for cancers with HRD.
Purpose of the Study:
- To conduct a meta-analysis evaluating the efficacy of olaparib monotherapy and combination therapies in lung cancer.
- To assess the impact of olaparib on progression-free survival (PFS) in NSCLC patients with HRD.
Main Methods:
- A comprehensive literature search was performed across PubMed, Scopus, and Google Scholar up to August 13, 2023.
- Screening of 5208 articles identified 9 relevant studies for meta-analysis.
- Data extraction and quality assessment were conducted on the selected studies.
Main Results:
- Olaparib monotherapy demonstrated an increase in PFS (ES= 7.76; 95% CI= 0.16 to 1.36; P=0.208).
- Olaparib maintenance therapy improved PFS compared to placebo in platinum-sensitive NSCLC patients (ES= 0.9; 95% CI= 0.9 to 0.9).
- Combination therapy with durvalumab or gefitinib did not significantly improve PFS compared to olaparib alone.
Conclusions:
- Olaparib monotherapy may improve PFS in lung cancer patients.
- Combination therapies of olaparib with gefitinib or durvalumab did not show significant PFS benefits.
- Further large-scale randomized controlled trials are needed due to study heterogeneity to confirm these findings.
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