TY - JOUR
T1 - First-line therapy for metastatic renal cell carcinoma
T2 - A propensity score-matched comparison of efficacy and safety
AU - On behalf of JK-FOOT study group
AU - Yanagisawa, Takafumi
AU - Mori, Keiichiro
AU - Kawada, Tatsushi
AU - Katayama, Satoshi
AU - Uchimoto, Taizo
AU - Tsujino, Takuya
AU - Nishimura, Kazuki
AU - Adachi, Takahiro
AU - Toyoda, Shingo
AU - Nukaya, Takuhisa
AU - Fukuokaya, Wataru
AU - Urabe, Fumihiko
AU - Murakami, Masaya
AU - Yamanoi, Tomoaki
AU - Bekku, Kensuke
AU - Komura, Kazumasa
AU - Takahara, Kiyoshi
AU - Hashimoto, Takeshi
AU - Fujita, Kazutoshi
AU - Azuma, Haruhito
AU - Ohno, Yoshio
AU - Shiroki, Ryoichi
AU - Uemura, Hirotsugu
AU - Araki, Motoo
AU - Kimura, Takahiro
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024/11
Y1 - 2024/11
N2 - Purpose: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. Methods: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. Results: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33–NA) in patients treated with ICI+ICI and was not reached (95%CI: 43–NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7–25) than for ICI+TKI (25 months, 95%CI: 13–NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). Conclusions: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.
AB - Purpose: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. Methods: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. Results: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33–NA) in patients treated with ICI+ICI and was not reached (95%CI: 43–NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7–25) than for ICI+TKI (25 months, 95%CI: 13–NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). Conclusions: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.
KW - Clear cell carcinoma
KW - Immune checkpoint inhibitor
KW - Metastatic renal cell carcinoma
KW - Propensity-score matching
KW - Tyrosine kinase inhibitor
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U2 - 10.1016/j.urolonc.2024.06.013
DO - 10.1016/j.urolonc.2024.06.013
M3 - Article
C2 - 39085019
AN - SCOPUS:85199951403
SN - 1078-1439
VL - 42
SP - 374.e21-374.e29
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 11
ER -