Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non–Squamous Non–Small Cell Lung Cancer
“…This reviewed process ( Figure 1 ) led to the selection of 32 articles, of which 19 studies were considered for final analysis of MACEs, 24 articles were considered for hypertension, 25 for thromboembolic events, and 17 for pulmonary embolism based on their adequate quality and relevance for inclusion in this meta-analysis. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 The characteristics of each trial analyzed in this study are shown in Table 1 . Figure 1 Selection of the included studies.…”
“…This reviewed process ( Figure 1 ) led to the selection of 32 articles, of which 19 studies were considered for final analysis of MACEs, 24 articles were considered for hypertension, 25 for thromboembolic events, and 17 for pulmonary embolism based on their adequate quality and relevance for inclusion in this meta-analysis. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 The characteristics of each trial analyzed in this study are shown in Table 1 . Figure 1 Selection of the included studies.…”
“…The five studies Ramalingam et al (2017) , Pietanza et al (2018) , Govindan et al (2022) , Argiris et al (2021) and Byers et al (2021) enrolled a total of 1,010 participants, with 537 in the experimental group and 473 in the control group. The experimental group received Veliparib combined with chemotherapy, whereas the control group was treated with placebo combined with chemotherapy.…”
Objective
Lung cancer, originating from bronchial mucosa or lung glands, poses significant health risks due to its rising incidence and mortality. This study aimed to assess the efficacy and safety of Veliparib combined with chemotherapy versus pharmacotherapy alone for lung cancer treatment, guiding clinical approaches for this severe disease.
Methods
Comprehensive searches in PubMed, EMBASE, Cochrane, and Web of Science were conducted to identify randomized controlled trials (RCTs) comparing Veliparib combined with standard chemotherapy to chemotherapy alone in lung cancer treatment, up until December 28, 2022. Two reviewers meticulously selected literature based on inclusion and exclusion criteria. The Cochrane tool was used to assess the bias risk of the included studies, and meta-analysis was performed using Stata 15.0.
Results
Five RCTs (1,010 participants) were included. The analysis results showed that only Veliparib combinedwith chemotherapy prolonged the progression-free survival (PFS) in small cell lung cancer (SCLC) patients [HR = 0.72, 95% CI = (0.57, 0.90)]. No significant differences were observed in overall survival (OS) and objective response rate (ORR). Veliparib and combined chemotherapy caused some side effects in patients with lung cancer, including leukopenia [RR = 2.12, 95% CI = (1.27, 3.55)], neutropenia [RR = 1.51, 95% CI = (1.01, 2.26)], anemia [RR = 1.71, 95% CI = (1.07, 3.07)], and thrombocytopenia [RR = 3.33, 95% CI = (1.19, 9.30)]. For non-small cell lung cancer (NSCLC) patients, there were no statistically significant differences in PFS, OS, or ORR between the experimental and control groups [HR = 0.97, 95% CI = (0.75, 1.27)].
Conclusion
The strategy of combining Veliparib with chemotherapy may, to some extent, prolong the PFS in lung cancer patients. However, this benefit is not observed in OS or ORR. Additionally, there are evident adverse reactions. Due to a limited number of the included studies, additional extensive multicenter RCTs are required to validate these results. PROSPERO registration number: CRD42023411510.
“…However, no therapeutic benefit of adding veliparib to first line chemotherapy in phase III trial, but risk of death was decreased by 34% in the LP521 population ( 110 ), and history of recent smoking was most predictive factor for veliparib-CP ( 111 ). In another phase III trial, there was no significant improvement of OS with veliparib plus chemotherapy in patients with nsqNSCLC, but improved OS in the LP52+ subgroup ( 112 ).…”
Section: Strategies For Targeting the Ddr In Nsclcmentioning
Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DDR) is essential to maintain of normal cell circulation. The presence of genomic instability, which results from defective DDR, is a critical characteristic of cancer. The changes promote the accumulation of mutations, which are implicated in cancer cells, but these may be exploited for anti-cancer therapies. NSCLC has a distinct genomic profile compared to other tumors, making precision medicine essential for targeting actionable gene mutations. Although various treatment options for NSCLC exist including chemotherapy, targeted therapy, and immunotherapy, drug resistance inevitably arises. The identification of deleterious DDR mutations in 49.6% of NSCLC patients has led to the development of novel target therapies that have the potential to improve patient outcomes. Synthetic lethal treatment using poly (ADP-ribose) polymerase (PARP) inhibitors is a breakthrough in biomarker-driven therapy. Additionally, promising new compounds targeting DDR, such as ATR, CHK1, CHK2, DNA-PK, and WEE1, had demonstrated great potential for tumor selectivity. In this review, we provide an overview of DDR pathways and discuss the clinical translation of DDR inhibitors in NSCLC, including their application as single agents or in combination with chemotherapy, radiotherapy, and immunotherapy.
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