Cargando…
Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer
BACKGROUND: Nivolumab plus ipilimumab (N‐I) or pembrolizumab (PEM) is associated with survival improvement as chemotherapy‐free, first‐line treatment for patients with advanced non‐small cell lung carcinoma (NSCLC) and positive programmed cell death ligand 1 (PD‐L1). However, no direct comparison da...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240850/ https://www.ncbi.nlm.nih.gov/pubmed/32508007 http://dx.doi.org/10.1002/ctm2.14 |
_version_ | 1783536970034577408 |
---|---|
author | Zhou, Yixin Zhang, Yaqiong Guo, Guifang Cai, Xiuyu Yu, Hui Cai, Yanyu Zhang, Bei Hong, Shaodong Zhang, Li |
author_facet | Zhou, Yixin Zhang, Yaqiong Guo, Guifang Cai, Xiuyu Yu, Hui Cai, Yanyu Zhang, Bei Hong, Shaodong Zhang, Li |
author_sort | Zhou, Yixin |
collection | PubMed |
description | BACKGROUND: Nivolumab plus ipilimumab (N‐I) or pembrolizumab (PEM) is associated with survival improvement as chemotherapy‐free, first‐line treatment for patients with advanced non‐small cell lung carcinoma (NSCLC) and positive programmed cell death ligand 1 (PD‐L1). However, no direct comparison data exist between these two regimens to inform clinical decisions. Therefore, we performed indirect comparison for N‐I versus PEM using frequentist methods. RESULTS: Three randomized trials (KEYNOTE‐024, KEYNOTE‐042, and CheckMate 227) involving 2372 patients were included. For patients with tumor PD‐L1 level of ≥1%, pooled meta‐analyses showed that both N‐I and PEM improved overall survival (OS) relative to chemotherapy (N‐I: hazard ratio [HR] 0.82, 95% CI 0.69‐0.97; PEM: HR 0.81, 95% CI 0.71‐0.93); whereas only N‐I significantly improved progression‐free survival (PFS) (N‐I: HR 0.79, 95% CI 0.65‐0.96; PEM: HR 1.07, 95% CI 0.94‐1.21). Neither N‐I nor PEM was associated with improved objective response rate (ORR) compared with chemotherapy (N‐I: relative risk [RR] 1.20, 95% CI 0.98‐1.46; PEM: RR 1.03, 95% CI 0.86‐1.23). Indirect comparisons showed that N‐I was associated with longer PFS than PEM (HR 0.77, 95% CI 0.62‐0.95). However, N‐I was not superior to PEM in terms of OS (HR 0.98, 95% CI 0.77‐1.24) and ORR (RR 1.17, 95% CI 0.89‐1.52). N‐I showed a less favorable toxicity profile relative to PEM (all grade adverse events: RR 1.28, 95% CI 1.17‐1.40). CONCLUSIONS: N‐I and PEM provide comparable OS benefit for PD‐L1‐positive NSCLC. N‐I further improves PFS relative to PEM but at meaningful cost of toxicities. |
format | Online Article Text |
id | pubmed-7240850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72408502020-06-01 Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer Zhou, Yixin Zhang, Yaqiong Guo, Guifang Cai, Xiuyu Yu, Hui Cai, Yanyu Zhang, Bei Hong, Shaodong Zhang, Li Clin Transl Med Research Articles BACKGROUND: Nivolumab plus ipilimumab (N‐I) or pembrolizumab (PEM) is associated with survival improvement as chemotherapy‐free, first‐line treatment for patients with advanced non‐small cell lung carcinoma (NSCLC) and positive programmed cell death ligand 1 (PD‐L1). However, no direct comparison data exist between these two regimens to inform clinical decisions. Therefore, we performed indirect comparison for N‐I versus PEM using frequentist methods. RESULTS: Three randomized trials (KEYNOTE‐024, KEYNOTE‐042, and CheckMate 227) involving 2372 patients were included. For patients with tumor PD‐L1 level of ≥1%, pooled meta‐analyses showed that both N‐I and PEM improved overall survival (OS) relative to chemotherapy (N‐I: hazard ratio [HR] 0.82, 95% CI 0.69‐0.97; PEM: HR 0.81, 95% CI 0.71‐0.93); whereas only N‐I significantly improved progression‐free survival (PFS) (N‐I: HR 0.79, 95% CI 0.65‐0.96; PEM: HR 1.07, 95% CI 0.94‐1.21). Neither N‐I nor PEM was associated with improved objective response rate (ORR) compared with chemotherapy (N‐I: relative risk [RR] 1.20, 95% CI 0.98‐1.46; PEM: RR 1.03, 95% CI 0.86‐1.23). Indirect comparisons showed that N‐I was associated with longer PFS than PEM (HR 0.77, 95% CI 0.62‐0.95). However, N‐I was not superior to PEM in terms of OS (HR 0.98, 95% CI 0.77‐1.24) and ORR (RR 1.17, 95% CI 0.89‐1.52). N‐I showed a less favorable toxicity profile relative to PEM (all grade adverse events: RR 1.28, 95% CI 1.17‐1.40). CONCLUSIONS: N‐I and PEM provide comparable OS benefit for PD‐L1‐positive NSCLC. N‐I further improves PFS relative to PEM but at meaningful cost of toxicities. John Wiley and Sons Inc. 2020-04-07 /pmc/articles/PMC7240850/ /pubmed/32508007 http://dx.doi.org/10.1002/ctm2.14 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Zhou, Yixin Zhang, Yaqiong Guo, Guifang Cai, Xiuyu Yu, Hui Cai, Yanyu Zhang, Bei Hong, Shaodong Zhang, Li Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title | Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title_full | Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title_fullStr | Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title_full_unstemmed | Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title_short | Nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for PD‐L1‐positive non‐small cell lung cancer |
title_sort | nivolumab plus ipilimumab versus pembrolizumab as chemotherapy‐free, first‐line treatment for pd‐l1‐positive non‐small cell lung cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240850/ https://www.ncbi.nlm.nih.gov/pubmed/32508007 http://dx.doi.org/10.1002/ctm2.14 |
work_keys_str_mv | AT zhouyixin nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT zhangyaqiong nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT guoguifang nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT caixiuyu nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT yuhui nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT caiyanyu nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT zhangbei nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT hongshaodong nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer AT zhangli nivolumabplusipilimumabversuspembrolizumabaschemotherapyfreefirstlinetreatmentforpdl1positivenonsmallcelllungcancer |