PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials
Background: Small Cell Lung Cancer (SCLC) is a neuroendocrine carcinoma characterized by aggressive behavior and poor prognosis with limited treatment options. Poly ADP-Ribose Polymerase inhibitors (PARPi) are novel anti-cancer agents that induce DNA damages and cause cell death in tumor cells with...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Cancer Treatment and Research Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294225000127 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823864262262521856 |
|---|---|
| author | Samuel Pratama Lowilius Wiyono Martien Silviandy Setiawan Brigitta Cindy Lauren |
| author_facet | Samuel Pratama Lowilius Wiyono Martien Silviandy Setiawan Brigitta Cindy Lauren |
| author_sort | Samuel Pratama |
| collection | DOAJ |
| description | Background: Small Cell Lung Cancer (SCLC) is a neuroendocrine carcinoma characterized by aggressive behavior and poor prognosis with limited treatment options. Poly ADP-Ribose Polymerase inhibitors (PARPi) are novel anti-cancer agents that induce DNA damages and cause cell death in tumor cells with impaired DNA repair, known as the synthetic lethality concept. This study aimed to analyze the efficacy and safety of PARPi for patients with SCLC from available clinical trial data. Methods: Studies reporting efficacy and safety of PARPi therapy for SCLC patients were searched across five databases with predetermined eligibility criteria in accordance with the PRISMA statement. Critical appraisal was done using suitable tools, outcomes were extracted, and analyzed. Results: Five randomized controlled clinical trials with 451 interventional patients and 308 control patients with SCLC were included. The analysis showed increased Progression-Free Survival (PFS) (RR 0.92 (95 %CI 0.84–1.00; p=0.05)) and Objective Response Rate (ORR) (RR 1.27 (95 %CI 1.07–1.50; p=0.007)), no significant difference in Overall Survival (OS) (RR 1.03 (95 %CI 0.92–1.15; p=0.60)), and an increased risk for serious Treatment Emergent Adverse Events (TEAEs) (RR 1.13 (95 %CI 0.95–1.35; p=0.16)) in PARPi-receiving SCLC patients. Amongst the hematologic toxicities, sub-analysis showed that thrombocytopenia had the highest risk, followed by neutropenia, anemia, leukopenia, and lymphopenia. Conclusion: The addition of PARPi in the chemotherapy regimen for patients with SCLC results in increased PFS and ORR, with no difference in OS and an increased risk of TEAEs. Further and larger clinical studies are needed to validate the efficacy and safety of PARPi therapy for SCLC patients. |
| format | Article |
| id | doaj-art-a04e5a4756d5483eb7285f72083e76e2 |
| institution | Kabale University |
| issn | 2468-2942 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj-art-a04e5a4756d5483eb7285f72083e76e22025-02-09T05:00:48ZengElsevierCancer Treatment and Research Communications2468-29422024-01-0142100874PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trialsSamuel Pratama0Lowilius Wiyono1Martien Silviandy Setiawan2Brigitta Cindy Lauren3Dr Abdul Aziz General Hospital, Singkawang City, West Borneo Province, Indonesia; Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Corresponding author: Dr Abdul Aziz General Hospital, Singkawang City, West Borneo 79123, Indonesia.Dr Abdul Aziz General Hospital, Singkawang City, West Borneo Province, Indonesia; Faculty of Medicine, University of Indonesia, Jakarta, IndonesiaDr Abdul Aziz General Hospital, Singkawang City, West Borneo Province, Indonesia; Faculty of Medicine, Pelita Harapan University, Banten, IndonesiaDr Abdul Aziz General Hospital, Singkawang City, West Borneo Province, IndonesiaBackground: Small Cell Lung Cancer (SCLC) is a neuroendocrine carcinoma characterized by aggressive behavior and poor prognosis with limited treatment options. Poly ADP-Ribose Polymerase inhibitors (PARPi) are novel anti-cancer agents that induce DNA damages and cause cell death in tumor cells with impaired DNA repair, known as the synthetic lethality concept. This study aimed to analyze the efficacy and safety of PARPi for patients with SCLC from available clinical trial data. Methods: Studies reporting efficacy and safety of PARPi therapy for SCLC patients were searched across five databases with predetermined eligibility criteria in accordance with the PRISMA statement. Critical appraisal was done using suitable tools, outcomes were extracted, and analyzed. Results: Five randomized controlled clinical trials with 451 interventional patients and 308 control patients with SCLC were included. The analysis showed increased Progression-Free Survival (PFS) (RR 0.92 (95 %CI 0.84–1.00; p=0.05)) and Objective Response Rate (ORR) (RR 1.27 (95 %CI 1.07–1.50; p=0.007)), no significant difference in Overall Survival (OS) (RR 1.03 (95 %CI 0.92–1.15; p=0.60)), and an increased risk for serious Treatment Emergent Adverse Events (TEAEs) (RR 1.13 (95 %CI 0.95–1.35; p=0.16)) in PARPi-receiving SCLC patients. Amongst the hematologic toxicities, sub-analysis showed that thrombocytopenia had the highest risk, followed by neutropenia, anemia, leukopenia, and lymphopenia. Conclusion: The addition of PARPi in the chemotherapy regimen for patients with SCLC results in increased PFS and ORR, with no difference in OS and an increased risk of TEAEs. Further and larger clinical studies are needed to validate the efficacy and safety of PARPi therapy for SCLC patients.http://www.sciencedirect.com/science/article/pii/S2468294225000127PARPiSmall-cell lung cancerEfficacyAdverse event |
| spellingShingle | Samuel Pratama Lowilius Wiyono Martien Silviandy Setiawan Brigitta Cindy Lauren PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials Cancer Treatment and Research Communications PARPi Small-cell lung cancer Efficacy Adverse event |
| title | PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials |
| title_full | PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials |
| title_fullStr | PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials |
| title_full_unstemmed | PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials |
| title_short | PARP inhibitors as therapy for small cell lung carcinoma: A systematic review and meta-analysis of clinical trials |
| title_sort | parp inhibitors as therapy for small cell lung carcinoma a systematic review and meta analysis of clinical trials |
| topic | PARPi Small-cell lung cancer Efficacy Adverse event |
| url | http://www.sciencedirect.com/science/article/pii/S2468294225000127 |
| work_keys_str_mv | AT samuelpratama parpinhibitorsastherapyforsmallcelllungcarcinomaasystematicreviewandmetaanalysisofclinicaltrials AT lowiliuswiyono parpinhibitorsastherapyforsmallcelllungcarcinomaasystematicreviewandmetaanalysisofclinicaltrials AT martiensilviandysetiawan parpinhibitorsastherapyforsmallcelllungcarcinomaasystematicreviewandmetaanalysisofclinicaltrials AT brigittacindylauren parpinhibitorsastherapyforsmallcelllungcarcinomaasystematicreviewandmetaanalysisofclinicaltrials |