Skip to main content

Advertisement

SpringerLink
Log in

Real-world efficacy and safety of nivolumab plus ipilimumab in untreated metastatic renal cell carcinoma, and the impact of previous nephrectomy on clinical outcome: Japanese multi-institutional retrospective study

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

In metastatic renal-cell carcinoma (mRCC), recent clinical trials have shown efficacy of first-line combination therapy, as evidenced by better clinical outcome over target therapy. However, there are insufficient real-world evidences in mRCC patients in Japan.

Methods

We performed a multicenter retrospective study of 72 mRCC patients who received nivolumab plus ipilimumab as first-line treatment between September 2018 and July 2021. Patient’s characteristics, clinical outcomes and safety were retrospectively reviewed. We analyzed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients treated with combination therapy.

Results

Of all patients, the median age was 70 years (range, 36–86) and the major type of histology was clear cell RCC (n = 55; 76.4%). Progressive disease (n = 25; 34.8%) and irAEs (n = 22; 30.6%) were the most common causes for discontinuing treatment. Median PFS and OS seemed similar between patients who discontinued treatment because of irAEs and for patients who did not (p = 0.360 and p = 0.069, respectively). Importantly, for patients with synchronous metastatic disease at diagnosis (n = 56), nephrectomy before initiating nivolumab plus ipilimumab had a significantly positive impact on better OS when compared to that in patients without nephrectomy (p = 0.028).

Conclusion

This study confirms efficacy and safety of nivolumab plus ipilimumab for mRCC patients in real-world settings. Furthermore, nivolumab plus ipilimumab was associated with a better outcome in patients who had undergone nephrectomy at diagnosis for synchronous mRCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ATB:

Antibiotics

ccRCC:

Clear cell renal carcinoma

CTCAE:

Common Terminology Criteria for Adverse Event

DCR:

Disease control rate

ICI:

Immune checkpoint inhibitor

irAEs:

Immune-related adverse events

mRCC:

Metastatic renal cell carcinoma

ORR:

Objective response rate

OS:

Overall survival

PD-1:

Programmed cell death-1

PFS:

Progression-free survival

RCC:

Renal cell carcinoma

References

  1. Siegel RL, Miller KD, Fuchs HE et al (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33

    Article  Google Scholar 

  2. Capitanio U, Bensalah K, Bex A et al (2019) Epidemiology of renal cell carcinoma. Eur Urol 75:74–84

    Article  Google Scholar 

  3. Ljungberg B, Albiges L, Abu-Ghanem Y et al (2019) European Association of Urology Guidelines on Renal Cell Carcinoma: the 2019 Update. Eur Urol 75:799–810

    Article  Google Scholar 

  4. Pichler M, Hutterer GC, Chromecki TF et al (2011) External validation of the Leibovich prognosis score for nonmetastatic clear cell renal cell carcinoma at a single European center applying routine pathology. J Urol 186:1773–1777

    Article  Google Scholar 

  5. Motzer RJ, Tannir NM, McDermott DF et al (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277–1290

    Article  CAS  Google Scholar 

  6. Motzer RJ, Penkov K, Haanen J et al (2019) Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380:1103–1115

    Article  CAS  Google Scholar 

  7. Rini BI, Plimack ER, Stus V et al (2019) Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380:1116–1127

    Article  CAS  Google Scholar 

  8. Choueiri TK, Powles T, Burotto M et al (2021) Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 384:829–841

    Article  CAS  Google Scholar 

  9. Motzer R, Alekseev B, Rha SY et al (2021) Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 384:1289–1300

    Article  CAS  Google Scholar 

  10. Motzer RJ, Rini BI, McDermott DF et al (2019) Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 20:1370–1385

    Article  CAS  Google Scholar 

  11. Kato R, Kojima T, Sazuka T et al (2021) A multicentre retrospective study of nivolumab plus ipilimumab for untreated metastatic renal cell carcinoma. Anticancer Res 41:6199–6209

    Article  CAS  Google Scholar 

  12. Tanaka T, Hatakeyama S, Numakura K et al (2020) Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: a multicenter retrospective study. Int J Urol 27:1095–1100

    Article  CAS  Google Scholar 

  13. Meerveld-Eggink A, Graafland N, Wilgenhof S et al (2022) Primary renal tumour response in patients treated with nivolumab and ipilimumab for metastatic renal cell carcinoma: real-world data assessment. Eur Urol Open Sci 35:54–58

    Article  Google Scholar 

  14. Ribas A, Wolchok JD (2018) Cancer immunotherapy using checkpoint blockade. Science 359:1350–1355

    Article  CAS  Google Scholar 

  15. Motzer RJ, Escudier B, McDermott DF et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813

    Article  CAS  Google Scholar 

  16. Kato T, Nagahara A, Kawamura N et al (2021) The prognostic impact of immune-related adverse events in metastatic renal cell carcinoma patients treated with nivolumab: a real-world multi-institutional retrospective study. Int J Clin Oncol 26:954–961

    Article  CAS  Google Scholar 

  17. Escudier B (2019) Combination therapy as first-line treatment in metastatic renal-cell carcinoma. N Engl J Med 380:1176–1178

    Article  Google Scholar 

  18. Schadendorf D, Wolchok JD, Hodi FS et al (2017) Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: a pooled analysis of randomized phase II and III trials. J Clin Oncol 35:3807–3814

    Article  CAS  Google Scholar 

  19. Hodi FS, Chiarion-Sileni V, Gonzalez R et al (2018) Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 19:1480–1492

    Article  CAS  Google Scholar 

  20. Paz-Ares LG, Ramalingam SS, Ciuleanu TE et al (2022) First-line nivolumab plus ipilimumab in advanced NSCLC: 4-year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial. J Thorac Oncol 17:289–308

    Article  CAS  Google Scholar 

  21. Stellato M, Santini D, Verzoni E et al (2021) Impact of previous nephrectomy on clinical outcome of metastatic renal carcinoma treated with immune-oncology: a real-world study on behalf of meet-URO group (MeetUro-7b). Front Oncol 11:682449

    Article  Google Scholar 

  22. Wald G, Barnes KT, Bing MT et al (2014) Minimal changes in the systemic immune response after nephrectomy of localized renal masses. Urol Oncol 32:589–600

    Article  Google Scholar 

  23. Motzer RJ, Escudier B, George S et al (2020) Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. https://doi.org/10.1002/cncr.33033

    Article  PubMed  Google Scholar 

  24. Pinato DJ, Gramenitskaya D, Altmann DM et al (2019) Antibiotic therapy and outcome from immune-checkpoint inhibitors. J Immunother Cancer 7:287

    Article  Google Scholar 

  25. Tsikala-Vafea M, Belani N, Vieira K et al (2021) Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Int J Infect Dis 106:142–154

    Article  CAS  Google Scholar 

  26. Pinato DJ, Howlett S, Ottaviani D et al (2019) Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol 5:1774–1778

    Article  Google Scholar 

  27. Sen S, Carmagnani Pestana R, Hess K et al (2018) Impact of antibiotic use on survival in patients with advanced cancers treated on immune checkpoint inhibitor phase I clinical trials. Ann Oncol 29:2396–2398

    Article  CAS  Google Scholar 

  28. Derosa L, Hellmann MD, Spaziano M et al (2018) Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol 29:1437–1444

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Suita, Japan

    Taigo Kato, Koji Hatano, Atsunari Kawashima, Ryoichi Imamura, Motohide Uemura & Norio Nonomura

  2. Department of Urology, Kindai University Faculty of Medicine, Sayama, Osaka, 589-8511, Japan

    Kazutoshi Fujita, Takafumi Minami & Hirotsugu Uemura

  3. Department of Urology, Osaka International Cancer Institute, Chuo-ku, Osaka, 541-8567, Japan

    Akira Nagahara, Yasutomo Nakai, Masashi Nakayama & Kazuo Nishimura

  4. Department of Urology, Osaka General Medical Center, Sumiyoshi-ku, Osaka, 558-8558, Japan

    Yujiro Hyashi & Tetsuya Takao

  5. Departments of Urology, Osaka Rosai Hospital, Sakai, Osaka, 591-8025, Japan

    Wataru Nakata & Masao Tsujihata

  6. Department of Urology, National Hospital Organization Osaka National Hospital, Chuo-ku, Osaka, 540-0006, Japan

    Kyosuke Matsuzaki & Kensaku Nishimura

  7. Department of Urology, Osaka Police Hospital, Tenoji-ku, Osaka, 543-0035, Japan

    Kosuke Nakano & Shingo Takada

Authors
  1. Taigo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazutoshi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takafumi Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akira Nagahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yujiro Hyashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wataru Nakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyosuke Matsuzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kosuke Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Koji Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Atsunari Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ryoichi Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shingo Takada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kensaku Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masao Tsujihata
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Tetsuya Takao
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yasutomo Nakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Masashi Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Kazuo Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Motohide Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Hirotsugu Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Norio Nonomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TK was responsible for the study conception and design, and conducted the study, data collection and analysis, drafting the manuscript. KF, AN, YH, WN, KM, KN, KH, AK, RI, ST, KN, MT, MT, TT, KN, YN, MN, MU, HM, NN conducted the study, data collection and analysis, drafting the manuscript, and manuscript revision. All authors read and approved the final manuscript for submission.

Corresponding author

Correspondence to Taigo Kato.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 80 KB)

Supplementary file2 (docx 16 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kato, T., Fujita, K., Minami, T. et al. Real-world efficacy and safety of nivolumab plus ipilimumab in untreated metastatic renal cell carcinoma, and the impact of previous nephrectomy on clinical outcome: Japanese multi-institutional retrospective study. Int J Clin Oncol 27, 1596–1604 (2022). https://doi.org/10.1007/s10147-022-02215-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-022-02215-8

Keywords

Search

Navigation