Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis
Introduction: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings. Methods: Extensive search...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2019-01-01
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| Series: | Indian Journal of Urology |
| Online Access: | http://www.indianjurol.com/article.asp?issn=0970-1591;year=2019;volume=35;issue=2;spage=101;epage=115;aulast=Pattanaik |
| _version_ | 1819081543961804800 |
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| author | Smita Pattanaik Sumit Dey Nishant Jaiswal Rachna Rohilla Shrawan Kumar Singh Arup Kumar Mandal Ravimohan Suryanarayan Mavuduru |
| author_facet | Smita Pattanaik Sumit Dey Nishant Jaiswal Rachna Rohilla Shrawan Kumar Singh Arup Kumar Mandal Ravimohan Suryanarayan Mavuduru |
| author_sort | Smita Pattanaik |
| collection | DOAJ |
| description | Introduction: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings.
Methods: Extensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis.
Results: Ten nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1–21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3–14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9–27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5–2.9 vs. 2.0–2.7 months and 7.9–18.2 vs. 15.9 months) and second-line chemotherapy (3.3–4.0 months and 7.4–8 months). Odds of achieving ORR was 0.10 (95% CI 0.03–0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19–0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible.
Conclusions: PD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care. |
| first_indexed | 2024-12-21T20:02:27Z |
| format | Article |
| id | doaj.art-606847c8144b41ce893739d9cffee15f |
| institution | Directory Open Access Journal |
| issn | 0970-1591 1998-3824 |
| language | English |
| last_indexed | 2024-12-21T20:02:27Z |
| publishDate | 2019-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Journal of Urology |
| spelling | doaj.art-606847c8144b41ce893739d9cffee15f2022-12-21T18:51:56ZengWolters Kluwer Medknow PublicationsIndian Journal of Urology0970-15911998-38242019-01-0135210111510.4103/iju.IJU_357_18Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysisSmita PattanaikSumit DeyNishant JaiswalRachna RohillaShrawan Kumar SinghArup Kumar MandalRavimohan Suryanarayan MavuduruIntroduction: Programmed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings. Methods: Extensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis. Results: Ten nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1–21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3–14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9–27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5–2.9 vs. 2.0–2.7 months and 7.9–18.2 vs. 15.9 months) and second-line chemotherapy (3.3–4.0 months and 7.4–8 months). Odds of achieving ORR was 0.10 (95% CI 0.03–0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19–0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible. Conclusions: PD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care.http://www.indianjurol.com/article.asp?issn=0970-1591;year=2019;volume=35;issue=2;spage=101;epage=115;aulast=Pattanaik |
| spellingShingle | Smita Pattanaik Sumit Dey Nishant Jaiswal Rachna Rohilla Shrawan Kumar Singh Arup Kumar Mandal Ravimohan Suryanarayan Mavuduru Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis Indian Journal of Urology |
| title | Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis |
| title_full | Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis |
| title_fullStr | Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis |
| title_full_unstemmed | Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis |
| title_short | Efficacy and safety of programmed cell death-1/programmed cell death ligand-1 inhibitors in advanced urothelial malignancy: A systematic review and meta-analysis |
| title_sort | efficacy and safety of programmed cell death 1 programmed cell death ligand 1 inhibitors in advanced urothelial malignancy a systematic review and meta analysis |
| url | http://www.indianjurol.com/article.asp?issn=0970-1591;year=2019;volume=35;issue=2;spage=101;epage=115;aulast=Pattanaik |
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