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First-line dual immune checkpoint inhibitor therapies versus combination therapies comprising immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced renal cell carcinoma: a comparative analysis of the effectiveness using real-world data

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Abstract

Background

There are few comparative studies on dual immune checkpoint inhibitors (ICIs) (i.e., IO-IO) and combination therapies comprising ICIs plus tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI) for advanced renal cell carcinoma (RCC), especially in real-world settings.

Methods

We retrospectively evaluated data of 175 patients with IMDC intermediate-risk or poor-risk RCC; as first-line therapy, 103 received IO-IO, and 72 received IO-TKI. An inverse probability of treatment weighting (IPTW) analysis was conducted to balance patients' backgrounds in the IO-IO and IO-TKI groups.

Results

Based on the IPTW analysis, progression-free survival (PFS) was longer in the IO-TKI group than in the IO-IO group (median: 15.6 vs. 8.3 months; p = 0.0386). In contrast, overall survival was not different between groups (median: 46.7 vs. 49.0 months; p = 0.465). Although the IPTW-adjusted objective response rate was not significantly different (51.2% vs. 43.9%; p = 0.359), the progressive disease rate as the best overall response was lower in the IO-TKI group than in the IO-IO group (3.3% vs. 27.4%; p < 0.0001). Regarding the safety profile, the treatment interruption rate was higher in the IO-TKI group than in the IO-IO group (70.3% vs. 49.2%; p = 0.005). In contrast, the IO-IO group had a higher corticosteroid administration rate (43.3% vs. 20.3%; p = 0.001).

Conclusion

IO-TKI therapy exhibited superior effectiveness over IO-IO therapy in terms of PFS improvement and immediate disease progression prevention and was associated with a higher risk of treatment interruption and a lower risk of needing corticosteroids.

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References

  1. Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378(14):1277–1290. https://doi.org/10.1056/NEJMoa1712126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rini BI, Plimack ER, Stus V et al (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1116–1127. https://doi.org/10.1056/NEJMoa1816714

    Article  CAS  PubMed  Google Scholar 

  3. Motzer RJ, Penkov K, Haanen J et al (2019) Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1103–1115. https://doi.org/10.1056/NEJMoa1816047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Choueiri TK, Powles T, Burotto M et al (2021) Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 384(9):829–841. https://doi.org/10.1056/NEJMoa2026982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Motzer R, Alekseev B, Rha SY et al (2021) Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 384(14):1289–1300. https://doi.org/10.1056/NEJMoa2035716

    Article  CAS  PubMed  Google Scholar 

  6. Motzer RJ, Jonasch E, Agarwal N et al (2022) Kidney cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 20(1):71–90. https://doi.org/10.6004/jnccn.2022.0001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rathmell WK, Rumble RB, Veldhuizen PJ et al (2022) Management of metastatic clear cell renal cell carcinoma: ASCO guideline. J Clin Oncol 40(25):2957–2995. https://doi.org/10.1200/jco.22.00868

    Article  CAS  PubMed  Google Scholar 

  8. Ljungberg B, Albiges L, Abu-Ghanem Y et al (2022) European Association of urology guidelines on renal cell carcinoma: the 2022 update. Eur Urol 82(4):399–410. https://doi.org/10.1016/j.eururo.2022.03.006

    Article  PubMed  Google Scholar 

  9. Shah NJ, Sura SD, Shinde R et al (2023) Real-world treatment patterns and clinical outcomes for metastatic renal cell carcinoma in the current treatment era. Eur Urol Open Sci 49:110–118. https://doi.org/10.1016/j.euros.2022.12.015

    Article  PubMed  PubMed Central  Google Scholar 

  10. Stühler V, Herrmann L, Rausch S et al (2022) Real world data on IO-based therapy for metastatic renal cell carcinoma. J Cancer Res Clin Oncol. https://doi.org/10.1007/s00432-022-04173-0

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ishihara H, Nemoto Y, Nakamura K et al (2022) Changes in real-world outcomes in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor era. Target Oncol 17(3):307–319. https://doi.org/10.1007/s11523-022-00879-w

    Article  PubMed  Google Scholar 

  12. Guida A, Sabbatini R, Gibellini L et al (2021) Finding predictive factors for immunotherapy in metastatic renal-cell carcinoma: what are we looking for? Cancer Treat Rev 94:102157. https://doi.org/10.1016/j.ctrv.2021.102157

    Article  CAS  PubMed  Google Scholar 

  13. Miao D, Margolis CA, Gao W et al (2018) Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 359(6377):801–806. https://doi.org/10.1126/science.aan5951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lombardi P, Filetti M, Falcone R et al (2022) New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network meta-analysis. Cancer Treat Rev 106:102377. https://doi.org/10.1016/j.ctrv.2022.102377

    Article  CAS  PubMed  Google Scholar 

  15. Nocera L, Karakiewicz PI, Wenzel M et al (2022) Clinical outcomes and adverse events after first-line treatment in metastatic renal cell carcinoma: a systematic review and network meta-analysis. J Urol 207(1):16–24. https://doi.org/10.1097/ju.0000000000002252

    Article  PubMed  Google Scholar 

  16. Quhal F, Mori K, Bruchbacher A et al (2021) First-line Immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network meta-analysis. Eur Urol Oncol 4(5):755–765. https://doi.org/10.1016/j.euo.2021.03.001

    Article  PubMed  Google Scholar 

  17. Bosma NA, Warkentin MT, Gan CL et al (2022) Efficacy and safety of first-line systemic therapy for metastatic renal cell carcinoma: a systematic review and network meta-analysis. Eur Urol Open Sci 37:14–26. https://doi.org/10.1016/j.euros.2021.12.007

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dudani S, Graham J, Wells JC et al (2019) First-line immuno-oncology combination therapies in metastatic renal-cell carcinoma: results from the international metastatic renal-cell carcinoma database consortium. Eur Urol 76(6):861–867. https://doi.org/10.1016/j.eururo.2019.07.048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shah NJ, Sura SD, Shinde R et al (2023) Real-world clinical outcomes of patients with metastatic renal cell carcinoma receiving pembrolizumab + axitinib vs. ipilimumab + nivolumab. Urol Oncol. https://doi.org/10.1016/j.urolonc.2023.08.009

    Article  PubMed  Google Scholar 

  20. Zarrabi KK, Handorf E, Miron B et al (2023) Comparative effectiveness of front-line ipilimumab and nivolumab or axitinib and pembrolizumab in metastatic clear cell renal cell carcinoma. Oncologist 28(2):157–164. https://doi.org/10.1093/oncolo/oyac195

    Article  PubMed  Google Scholar 

  21. Santoni M, Massari F, Myint ZW et al (2023) Global real-world outcomes of patients receiving immuno-oncology combinations for advanced renal cell carcinoma: the ARON-1 study. Target Oncol 18(4):559–570. https://doi.org/10.1007/s11523-023-00978-2

    Article  PubMed  Google Scholar 

  22. Santoni M, Buti S, Myint ZW et al (2023) Real-world outcome of patients with advanced renal cell carcinoma and intermediate- or poor-risk international metastatic renal cell carcinoma database consortium criteria treated by immune-oncology combinations: differential effectiveness by risk group? Eur Urol Oncol. https://doi.org/10.1016/j.euo.2023.07.003

    Article  PubMed  Google Scholar 

  23. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 11). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  24. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.4 (http://evs.nci.nih.gov/ftp1/CTCAE/About.html).

  25. Ishihara H, Nemoto Y, Nakamura K et al (2023) Comparison of outcomes between therapeutic combinations based on immune checkpoint inhibitors or tyrosine kinase inhibitor monotherapy for first-line therapy of patients with advanced renal cell carcinoma outside of clinical trials: a real-world retrospective multi-institutional study. Target Oncol 18(2):209–220. https://doi.org/10.1007/s11523-023-00956-8

    Article  PubMed  Google Scholar 

  26. Numakura K, Sekine Y, Hatakeyama S et al (2023) Primary resistance to nivolumab plus ipilimumab therapy in patients with metastatic renal cell carcinoma. Cancer Med 12(16):16837–16845. https://doi.org/10.1002/cam4.6306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Michot JM, Bigenwald C, Champiat S et al (2016) Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54:139–148. https://doi.org/10.1016/j.ejca.2015.11.016

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Ms. Nobuko Hata (Department of Urology, Tokyo Women’s Medical University) for her secretarial work.

Funding

This study did not receive any funding.

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Authors and Affiliations

  1. Department of Urology, Tokyo Women’s Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, Japan

    Hiroki Ishihara, Takashi Ikeda, Yuki Kobari, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka & Toshio Takagi

  2. Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Fukushima, Japan

    Kenji Omae

  3. Department of Urology, Tokyo Women’s Medical University Adachi Medical Center, 4-33-1 Kouhoku, Adachi-Ku, Tokyo, Japan

    Yuki Nemoto, Koichi Nishimura & Tsunenori Kondo

  4. Department of Urology, Saiseikai Kazo Hospital, 1680 Kamitakayanagi, Kazo, Saitama, Japan

    Ryo Ishiyama & Hidekazu Tachibana

  5. Department of Urology, Jyoban Hospital, Uenodai 57, Joban Kamiyunagayamachi, Iwaki, Fukushima, Japan

    Hiroaki Shimmura

  6. Department of Urology, Saiseikai Kawaguchi General Hospital, 5-11-5 Nishikawaguchi, Kawaguchi, Saitama, Japan

    Yasunobu Hashimoto

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  1. Hiroki Ishihara
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  3. Yuki Nemoto
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Corresponding author

Correspondence to Hiroki Ishihara.

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Conflict of interest

Toshio Takagi received honoraria from Bristol-Myers Squibb and Ono Pharmaceutical. Tsunenori Kondo received honoraria from Pfizer, Novartis, Bristol-Myers Squibb, and Ono Pharmaceutical. Kenji Omae received honoraria from Pfizer and Ono Pharmaceutical outside the submitted work. No other disclosures were reported.

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Ishihara, H., Omae, K., Nemoto, Y. et al. First-line dual immune checkpoint inhibitor therapies versus combination therapies comprising immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced renal cell carcinoma: a comparative analysis of the effectiveness using real-world data. Int J Clin Oncol 29, 473–480 (2024). https://doi.org/10.1007/s10147-024-02471-w

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