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Comparative Study
. 2025 Jan 22;25(1):117.
doi: 10.1186/s12885-025-13504-6.

Real-world short-term outcomes and treatment regimen comparisons in patients with metastatic renal cell carcinoma treated with first-line immune combinations

Masato Kikuta  1 , Sei Naito  2 , Takahiro Osawa  3 , Kazuyuki Numakura  4 , Takafumi Narisawa  1 , Yuki Takai  1 , Mayu Yagi  1 , Yuya Sekine  4 , Ojiro Tokairin  3 , Nobuo Shinohara  3 , Tomonori Habuchi  4 , Norihiko Tsuchiya  1
Affiliations
Comparative Study

Real-world short-term outcomes and treatment regimen comparisons in patients with metastatic renal cell carcinoma treated with first-line immune combinations

Masato Kikuta et al. BMC Cancer. .

Abstract

Background: Immune-combinations have recently become the standard first-line treatment for patients with metastatic renal cell carcinoma (mRCC). This study evaluated the applicability of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model in predicting outcomes for patients treated with either immune-oncologic drug doublet (IO-IO) or immune-oncologic drug tyrosine kinase inhibitor combinations (IO-TKI). A secondary objective to compare the effectiveness of IO-IO versus IO-TKI within the IMDC risk groups over a short follow-up period.

Methods: A retrospective analysis was conducted on 172 patients with mRCC treated with first-line immunotherapy combinations. Progression free survival (PFS), time to treatment failure 2 (TTF2), and overall survival (OS) were compared between IMDC risk categories. Model fit was assessed using the c-index. The inverse probability of treatment weighting (IPTW) method was used to adjust and compare outcomes between IO-IO and IO-TKI, except for IMDC favorable risk patients due to the small number of IO-IO cases.

Results: The IMDC risk model demonstrated a c-index of 0.684 (OS) for entire cohort, 0.600 (PFS), 0.596 (TTF2), and 0.624 (OS) for IO-IO, and 0.667 (PFS), 0.702 (TTF2), and 0.751 (OS) for IO-TKI. In the IMDC intermediate and poor risk groups after IPTW adjustment, PFS (HR 0.72), TTF2 (HR 0.67), and OS (HR 0.74) did not significantly differ between IO-IO and IO-TKI. Specifically, in the IMDC intermediate risk group, PFS (HR 0.79), TTF2 (HR 0.69), and OS (HR 0.65) were longer in IO-TKI, though the differences were not statistically significant. In the IMDC poor risk group, PFS (HR 0.76), TTF2 (HR 0.77), and OS (HR 1.03) were comparable.

Conclusions: The impact of IMDC risk model on survival was modest in IO-IO, while remained statistically substantial in IO-TKI. Survival outcomes did not significantly differ between IO-IO and IO-TKI during the short follow-up period.

Keywords: Comparison; Immune-combinations; Immunotherapy; Prognosis; Renal cell carcinoma; Tyrosine kinase inhibitor.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Ethics Committee of Hokkaido University approved this study (Approval no, 023–0105). Informed consent was waved by using the opt-out method for this retrospective study. Consent for publication: Not applicable. Competing interests: Sei Naito received honoraria from Pfizer Japan Inc., Merk biopharma Japan Inc., Bristol Meier’s squibb Japan Inc., Ono Pharma, MSD Japan, and Eisai Co. as their sponsored speaker. Takahiro Osawa received honoraria from MSD Japan. Nobuo Shinohara received honoraria from Pfizer, Ono, BMS, MSD, Takeda, Novartis, Eisai, Astra Zeneca, Bayer, Astellas, as their sponsored speaker and research funds from Ono and Takeda. Tomonori Habuchi received honoraria from Astellas, Ono, Janssen, as their sponsored speaker, and research funds from Sysmex and Mochida. Norihiko Tsuchiya received honoraria from Pfizer Japan Inc. Janssen, Novartis, Ono, Bayer, Sanofi, Takeda Pharm, Bristol-Myers Squibb Japan, and Astelas Pharma., as their sponsored speaker and research funds from Pfizer Japan Inc. and Eisai outside the submitted work. The other authors have declared that no conflict of interest exists.

Figures

Fig. 1
Fig. 1
Flow chart of the literature selection process
Fig. 2
Fig. 2
Overall survival in all patients with metastatic renal cell carcinoma (a), in each IMDC risk group (b), and in each Meet-URO score. Abbreviations: IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; Fav., favorable risk; Int., intermediate risk; Poor, poor risk; MeetUro, Meet-URO score; G1, group1 in Meet-URO score (no risk factor or bone metastasis); G2, Group 2 in Meet-URO score (IMDC intermediate or > = 3.2 NLR); G3, group 3 in Meet-URO score (IMDC intermediate + [bone metastasis or > = 3.2 NLR); G4, group 4 in Meet-URO score (IMDC intermediate + bone metastasis + > = 3.2 NLR or IMDC poor or IMDC poor + [bone metastasis or > = 3.2 NLR]); G5, Group 5 in Meet-URO score (IMDC poor + bone metastasis + > = 3.2 NLR)
Fig. 3
Fig. 3
Comparisons between each IMDC risk group in each IO-IO and IO-TKI group. a Comparison on PFS in IO-IO group. b Comparison on TTF2 in IO-IO group. c Comparison on OS in IO-IO group. d Comparison on PFS in IO-TKI group. e Comparison on TTF2 in IO-IO group. f Comparison on OS in IO-TKI group. Abbreviations: IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; Fav., favorable risk; Int., intermediate risk; Poor., poor risk; IO-IO, immune-oncology drug doublet; IO-TKI; combinations of an immune-oncologic drug and a tyrosine kinase inhibitor; PFS, progression free survival; TTF2, time to treatment failure 2; OS, overall survival; HR, hazard ratio; CI, confidence interval
Fig. 4
Fig. 4
Comparisons between IO-IO and IO-TKI groups in patients with IMDC intermediate/poor risk, adjusted IPTW method. a Distributions of propensity score. b IPTW adjusted PFS in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. c IPTW adjusted TTF2 in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. d IPTW adjusted OS in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. Abbreviations: IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IOIO, immune-oncology drug doublet; IO-TKI; combinations of an immune-oncologic drug and a tyrosine kinase inhibitor; PFS, progression free survival; TTF2, time to treatment failure 2; OS, overall survival; HR, hazard ratio; CI, confidence interval
Fig. 5
Fig. 5
Comparisons between IO-IO and IO-TKI groups in patients with IMDC intermediate risk, adjusted IPTW method. a Distributions of propensity score. b IPTW adjusted PFS in patients with IMDC intermediate/poor risk compared IOIO and IOTKI. c IPTW adjusted TTF2 in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. d IPTW adjusted OS in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. Abbreviations: IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IO-IO, immune-oncology drug doublet; IO-TKI; combinations of an immune-oncologic drug and a tyrosine kinase inhibitor; PFS, progression free survival; TTF2, time to treatment failure 2; OS, overall survival; HR, hazard ratio; CI, confidence interval
Fig. 6
Fig. 6
Comparisons between IO-IO and IO-TKI groups in patients with IMDC poor risk, adjusted IPTW method. a Distributions of propensity score. b IPTW adjusted PFS in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. c IPTW adjusted TTF2 in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. d IPTW adjusted OS in patients with IMDC intermediate/poor risk compared IO-IO and IO-TKI. Abbreviations: IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IO-IO, immune-oncology drug doublet; IO-TKI; combinations of an immune-oncologic drug and a tyrosine kinase inhibitor; PFS, progression free survival; TTF2, time to treatment failure 2; OS, overall survival; HR, hazard ratio; CI, confidence interval
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