Progression-Free and Overall Survival of First-Line Treatments for Advanced Renal Cell Carcinoma: Indirect Comparison of Six Combination Regimens.
Shiny method
combination
indirect comparison
overall survival
reconstructed individual patient data
renal cell carcinoma
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
29 Mar 2023
29 Mar 2023
Historique:
received:
16
02
2023
revised:
21
03
2023
accepted:
28
03
2023
medline:
14
4
2023
entrez:
13
4
2023
pubmed:
14
4
2023
Statut:
epublish
Résumé
Recently, numerous combination therapies based on immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors have been proposed as first-line treatments for advanced renal cell carcinoma (aRCC). Our study aimed to compare the efficacy of these combination regimens by the application of an innovative method that reconstructs individual patient data. Six phase III studies describing different combination regimens for aRCC were selected. Individual patient data were reconstructed from Kaplan-Meier (KM) curves through the "Shiny method". Overall survival (OS) and progression-free survival (PFS) were compared among combination treatments and sunitinib. Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. In the overall population of aRCC patients, pembrolizumab + lenvatinib showed the longest median PFS and was expected to determine the longest OS. Pembrolizumab + axitinib, nivolumab + cabozantinib and nivolumab + ipilimumab were similar in terms of PFS, but pembrolizumab + axitinib also demonstrated a better OS. Our subgroup analysis showed that sunitinib is still a valuable option, whereas, in intermediate-poor risk patients, pembrolizumab + axitinib and nivolumab + ipilimumab significantly improve OS compared to sunitinib. The Shiny method allowed us to perform all head-to-head indirect comparisons between these agents in a context in which "real" comparative trials have not been performed.
Sections du résumé
BACKGROUND
BACKGROUND
Recently, numerous combination therapies based on immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors have been proposed as first-line treatments for advanced renal cell carcinoma (aRCC). Our study aimed to compare the efficacy of these combination regimens by the application of an innovative method that reconstructs individual patient data.
METHODS
METHODS
Six phase III studies describing different combination regimens for aRCC were selected. Individual patient data were reconstructed from Kaplan-Meier (KM) curves through the "Shiny method". Overall survival (OS) and progression-free survival (PFS) were compared among combination treatments and sunitinib. Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity.
RESULTS
RESULTS
In the overall population of aRCC patients, pembrolizumab + lenvatinib showed the longest median PFS and was expected to determine the longest OS. Pembrolizumab + axitinib, nivolumab + cabozantinib and nivolumab + ipilimumab were similar in terms of PFS, but pembrolizumab + axitinib also demonstrated a better OS. Our subgroup analysis showed that sunitinib is still a valuable option, whereas, in intermediate-poor risk patients, pembrolizumab + axitinib and nivolumab + ipilimumab significantly improve OS compared to sunitinib.
CONCLUSION
CONCLUSIONS
The Shiny method allowed us to perform all head-to-head indirect comparisons between these agents in a context in which "real" comparative trials have not been performed.
Identifiants
pubmed: 37046690
pii: cancers15072029
doi: 10.3390/cancers15072029
pmc: PMC10093553
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Eur Urol Open Sci. 2022 Jan 22;37:14-26
pubmed: 35128482
N Engl J Med. 2021 Apr 8;384(14):1289-1300
pubmed: 33616314
Eur Urol Oncol. 2021 Oct;4(5):755-765
pubmed: 33757737
Lancet. 2019 Jun 15;393(10189):2404-2415
pubmed: 31079938
Cancer. 2022 Jun 1;128(11):2085-2097
pubmed: 35383908
Ann Oncol. 2020 Aug;31(8):1030-1039
pubmed: 32339648
BMC Med Res Methodol. 2021 Jun 1;21(1):111
pubmed: 34074267
Cureus. 2021 Nov 9;13(11):e19422
pubmed: 34786276
Cureus. 2022 Aug 25;14(8):e28369
pubmed: 36171827
Stroke. 2023 Feb;54(2):457-467
pubmed: 36647921
Cancers (Basel). 2022 Dec 14;14(24):
pubmed: 36551652
Lancet Oncol. 2022 Jul;23(7):888-898
pubmed: 35688173
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Liver Cancer. 2022 Aug 23;12(1):7-18
pubmed: 36872922
Eur Urol. 2021 Oct;80(4):393-397
pubmed: 34074559
Lancet Oncol. 2022 Jun;23(6):768-780
pubmed: 35489363
J Clin Med. 2022 Dec 27;12(1):
pubmed: 36615005
Curr Opin Urol. 2021 Jul 1;31(4):332-339
pubmed: 33965978
BMJ. 2015 Jan 02;350:g7647
pubmed: 25555855
Oncologist. 2023 Feb 8;28(2):157-164
pubmed: 36200791
BMJ. 2022 Jul 27;378:e069503
pubmed: 35896188
Lancet Oncol. 2020 Dec;21(12):1563-1573
pubmed: 33284113
Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-11
pubmed: 33793313
Cancers (Basel). 2023 Mar 07;15(6):
pubmed: 36980518
JAMA Oncol. 2023 Feb 1;9(2):215-224
pubmed: 36480211
Expert Rev Pharmacoecon Outcomes Res. 2022 Jan;22(1):45-51
pubmed: 34058953
World J Urol. 2022 Oct;40(10):2381-2386
pubmed: 35562599
Recenti Prog Med. 2022 Nov;113(11):680-687
pubmed: 36318172
JTCVS Open. 2022 Oct 28;12:177-191
pubmed: 36590724
Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-18
pubmed: 32243201