Efficacy of anti‑PD‑1 antibody nivolumab in Japanese patients with metastatic renal cell carcinoma: A retrospective multicenter analysis

  • Authors:
    • Kazuyuki Numakura
    • Yohei Horikawa
    • Sachiko Kamada
    • Atsushi Koizumi
    • Taketoshi Nara
    • Syuji Chiba
    • Sohei Kanda
    • Mitsuru Saito
    • Shintaro Narita
    • Takamitsu Inoue
    • Naotake Shimoda
    • Tomonori Habuchi
  • View Affiliations

  • Published online on: June 25, 2019     https://doi.org/10.3892/mco.2019.1887
  • Pages: 320-324
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Abstract

To evaluate the efficacy and safety of anti‑PD1 therapy (nivolumab) in advanced renal cell carcinoma (RCC) in a clinical setting. Between March 2013 and January 2018, 33 patients with RCC (27 men and 6 women) were treated with nivolumab. Before anti‑PD1 treatment, 12, 9 and 12 patients received one, two, and three or more therapies, respectively. Objective response, survival rate, and clinical adverse events were evaluated by the revised RECIST criteria (version 1.1). The median patient age was 68 years (range: 37‑79). In total, 14 (42%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 while 17 (52%) and two (6%) had an ECOG PS of 1 and 2 or higher, respectively. One (3%), 24 (73%) and eight (24%) were classified as having favorable, intermediate, and poor risk, respectively. The median follow‑up duration after nivolumab initiation was 26 months (range: 1‑131). The median progression‑free and overall survival were 10.3 months and 45.9 months, respectively. Nivolumab was associated with a disease control rate of 58%, with an objective response of 24% (complete response, 1; partial response, 7; stable disease, 11; progressive disease, 10; not assessed, 4). A total of 15 (46%) patients experienced adverse events, of which six were severe (grade 3 or more) and 10 were immunotherapy‑related. This study examined the initial experience of nivolumab administration in Japanese patients with advanced RCC. Our results suggest that nivolumab can achieve acceptable outcomes in a real clinical setting, with outcomes that are comparable to those of clinical trials.

References

1 

Powles T, Staehler M, Ljungberg B, Bensalah K, Canfield SE, Dabestani S, Giles R, Hofmann F, Hora M, Kuczyk MA, et al: Updated EAU guidelines for clear cell renal cancer patients who fail VEGF targeted therapy. Eur Urol. 69:4–6. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Motzer RJ, Jonasch E, Agarwal N, Bhayani S, Bro WP, Chang SS, Choueiri TK, Costello BA, Derweesh IH, Fishman M, et al: Kidney cancer, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 15:804–834. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Vachhani P and George S: VEGF inhibitors in renal cell carcinoma. Clin Adv Hematol Oncol. 14:1016–1028. 2016.PubMed/NCBI

4 

Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al: Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 373:1803–1813. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M, Tanabe K, Kimura G, Yonese J, Yao M, et al: Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study. Jpn J Clin Oncol. 47:639–646. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Sharma P and Allison JP: The future of immune checkpoint therapy. Science. 348:56–61. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Riaz N, Havel JJ, Makarov V, Desrichard A, Urba WJ, Sims JS, Hodi FS, Martín-Algarra S, Mandal R, Sharfman WH, et al: Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell. 171:934–949, e916. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Boutsikou E, Domvri K, Hardavella G, Tsiouda D, Zarogoulidis K and Kontakiotis T: Tumour necrosis factor, interferon-gamma and interleukins as predictive markers of antiprogrammed cell-death protein-1 treatment in advanced non-small cell lung cancer: A pragmatic approach in clinical practice. Ther Adv Med Oncol. 10:17588359187682382018. View Article : Google Scholar : PubMed/NCBI

9 

Remon J and Besse B: Immune checkpoint inhibitors in first-line therapy of advanced non-small cell lung cancer. Curr Opin Oncol. 29:97–104. 2017.PubMed/NCBI

10 

Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, et al: Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in checkmate 025. Eur Urol. 72:368–376. 2017. View Article : Google Scholar : PubMed/NCBI

11 

George S, Motzer RJ, Hammers HJ, Redman BG, Kuzel TM, Tykodi SS, Plimack ER, Jiang J, Waxman IM and Rini BI: Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression: A subgroup analysis of a randomized clinical trial. JAMA Oncol. 2:1179–1186. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Friedman CF, Proverbs-Singh TA and Postow MA: Treatment of the immune-related adverse effects of immune checkpoint inhibitors: A review. JAMA Oncol. 2:1346–1353. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Sarocchi M, Grossi F, Arboscello E, Bellodi A, Genova C, Dal Bello MG, Rijavec E, Barletta G, Rossi G, Biello F, et al: Serial troponin for early detection of nivolumab cardiotoxicity in advanced non-small cell lung cancer patients. Oncologist. 23:936–942. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Gauci ML, Laly P, Vidal-Trecan T, Baroudjian B, Gottlieb J, Madjlessi-Ezra N, Da Meda L, Madelaine-Chambrin I, Bagot M, Basset-Seguin N, et al: Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: A case report and literature review. Cancer Immunol Immunother. 66:1399–1410. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Makarious D, Horwood K and Coward JIG: Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors. Eur J Cancer. 82:128–136. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Spain L, Diem S and Larkin J: Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 44:51–60. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, Xu H, Yao S, Pons A, Chen L, et al: Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res. 19:462–468. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Martini DJ, Hamieh L, McKay RR, Harshman LC, Brandao R, Norton CK, Steinharter JA, Krajewski KM, Gao X, Schutz FA, et al: Durable clinical benefit in metastatic renal cell carcinoma patients who discontinue PD-1/PD-L1 therapy for immune-related adverse events. Cancer Immunol Res. 6:402–408. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, et al: STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 8:822–835. 2018. View Article : Google Scholar : PubMed/NCBI

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September 2019
Volume 11 Issue 3

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Copy and paste a formatted citation
APA
Numakura, K., Horikawa, Y., Kamada, S., Koizumi, A., Nara, T., Chiba, S. ... Habuchi, T. (2019). Efficacy of anti‑PD‑1 antibody nivolumab in Japanese patients with metastatic renal cell carcinoma: A retrospective multicenter analysis. Molecular and Clinical Oncology, 11, 320-324. https://doi.org/10.3892/mco.2019.1887
MLA
Numakura, K., Horikawa, Y., Kamada, S., Koizumi, A., Nara, T., Chiba, S., Kanda, S., Saito, M., Narita, S., Inoue, T., Shimoda, N., Habuchi, T."Efficacy of anti‑PD‑1 antibody nivolumab in Japanese patients with metastatic renal cell carcinoma: A retrospective multicenter analysis". Molecular and Clinical Oncology 11.3 (2019): 320-324.
Chicago
Numakura, K., Horikawa, Y., Kamada, S., Koizumi, A., Nara, T., Chiba, S., Kanda, S., Saito, M., Narita, S., Inoue, T., Shimoda, N., Habuchi, T."Efficacy of anti‑PD‑1 antibody nivolumab in Japanese patients with metastatic renal cell carcinoma: A retrospective multicenter analysis". Molecular and Clinical Oncology 11, no. 3 (2019): 320-324. https://doi.org/10.3892/mco.2019.1887