IO-IO vs IO-TKI efficacy in metastatic kidney cancer patients: A structured systematic review over time
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IO-IO vs IO-TKI efficacy in metastatic kidney cancer patients: A structured systematic review over time. / Hoeh, Benedikt; Flammia, Rocco Simone; Hohenhorst, Lukas; Sorce, Gabriele; Panunzio, Andrea; Tappero, Stefano; Tian, Zhe; Saad, Fred; Gallucci, Michele; Briganti, Alberto; Terrone, Carlo; Shariat, Shahrokh F; Graefen, Markus; Tilki, Derya; Antonelli, Alessandro; Kosiba, Marina; Kluth, Luis A; Becker, Andreas; Chun, Felix K H; Karakiewicz, Pierre I.
In: SEMIN ONCOL, Vol. 49, No. 5, 10.2022, p. 394-399.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - IO-IO vs IO-TKI efficacy in metastatic kidney cancer patients: A structured systematic review over time
AU - Hoeh, Benedikt
AU - Flammia, Rocco Simone
AU - Hohenhorst, Lukas
AU - Sorce, Gabriele
AU - Panunzio, Andrea
AU - Tappero, Stefano
AU - Tian, Zhe
AU - Saad, Fred
AU - Gallucci, Michele
AU - Briganti, Alberto
AU - Terrone, Carlo
AU - Shariat, Shahrokh F
AU - Graefen, Markus
AU - Tilki, Derya
AU - Antonelli, Alessandro
AU - Kosiba, Marina
AU - Kluth, Luis A
AU - Becker, Andreas
AU - Chun, Felix K H
AU - Karakiewicz, Pierre I
N1 - Copyright © 2022 Elsevier Inc. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been compared in a structured fashion. To assess OS and progression free survival (PFS) efficacy as reflected by hazard ratios [HR]) according to the duration of follow-up over time for each of four IO combination therapies. A systematic PubMed (MEDLINE) literature review was performed (January, 1, 2016 to February, 20, 2022). Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included. These search criteria yielded four eligible RCTs: CheckMate 214 (nivolumab plus ipilimumab), Keynote 426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), CLEAR (lenvatinib plus pembrolizumab). OS and PFS HRs were tabulated for all four studies including all reported timepoints. Median follow-up ranged from 25-68 months for CheckMate 214 (5 timepoints), 13-43 months for Keynote 426 (3 timepoints), 18-33 months for CheckMate 9ER (3 timepoints) and 27-34 months for CLEAR (2 timepoints). Respective OS and PFS HRs were 0.68-0.72 and 0.98-0.86, 0.53-0.73 and 0.69-0.68, 0.60-0.70 and 0.51-0.56, 0.66-0.72 and 0.39-0.47 for CheckMate 214, Keynote 426, CheckMate 9ER and CLEAR. Regarding OS HRs virtually no change was recorded over time for CheckMate 214, but a decrease in magnitude occurred in the three IO-TKI remaining studies. Regarding PFS HRs, no benefit was recorded for CheckMate 214. Statistically significant benefit was recorded in the remaining IO-TKI studies. However, it also decreased with longer follow-up. It remains to be seen, whether further 'slippage' of efficacy will persist as the data matures further for all IO-TKI combinations.
AB - Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been compared in a structured fashion. To assess OS and progression free survival (PFS) efficacy as reflected by hazard ratios [HR]) according to the duration of follow-up over time for each of four IO combination therapies. A systematic PubMed (MEDLINE) literature review was performed (January, 1, 2016 to February, 20, 2022). Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included. These search criteria yielded four eligible RCTs: CheckMate 214 (nivolumab plus ipilimumab), Keynote 426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), CLEAR (lenvatinib plus pembrolizumab). OS and PFS HRs were tabulated for all four studies including all reported timepoints. Median follow-up ranged from 25-68 months for CheckMate 214 (5 timepoints), 13-43 months for Keynote 426 (3 timepoints), 18-33 months for CheckMate 9ER (3 timepoints) and 27-34 months for CLEAR (2 timepoints). Respective OS and PFS HRs were 0.68-0.72 and 0.98-0.86, 0.53-0.73 and 0.69-0.68, 0.60-0.70 and 0.51-0.56, 0.66-0.72 and 0.39-0.47 for CheckMate 214, Keynote 426, CheckMate 9ER and CLEAR. Regarding OS HRs virtually no change was recorded over time for CheckMate 214, but a decrease in magnitude occurred in the three IO-TKI remaining studies. Regarding PFS HRs, no benefit was recorded for CheckMate 214. Statistically significant benefit was recorded in the remaining IO-TKI studies. However, it also decreased with longer follow-up. It remains to be seen, whether further 'slippage' of efficacy will persist as the data matures further for all IO-TKI combinations.
KW - Humans
KW - Antineoplastic Agents/therapeutic use
KW - Carcinoma, Renal Cell/drug therapy
KW - Kidney Neoplasms/drug therapy
KW - Nivolumab/therapeutic use
KW - Sunitinib/therapeutic use
U2 - 10.1053/j.seminoncol.2022.10.001
DO - 10.1053/j.seminoncol.2022.10.001
M3 - SCORING: Review article
C2 - 36333148
VL - 49
SP - 394
EP - 399
JO - SEMIN ONCOL
JF - SEMIN ONCOL
SN - 0093-7754
IS - 5
ER -
