Treatment outcomes of metastatic nonclear cell renal cell carcinoma: A single institution retrospective analysis

Vivek Agarwala; Anant Ramaswamy; Amit Joshi; Vijay Maruti Patil; Vanita Noronha; Santosh Menon; B. Palak Popat; Sable Nilesh; Kumar Prabhash

doi:10.4103/sajc.sajc_22_18

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ORIGINAL ARTICLE: Genitourinary Cancers

07 (

); 226-230

doi:

10.4103/sajc.sajc_22_18

Treatment outcomes of metastatic nonclear cell renal cell carcinoma: A single institution retrospective analysis

Vivek Agarwala¹, Anant Ramaswamy¹, Amit Joshi¹, Vijay Maruti Patil¹, Vanita Noronha¹, Santosh Menon², B. Palak Popat³, Sable Nilesh³, Kumar Prabhash^1,

1 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra

2 Department of Pathology, Tata Memorial Centre, Mumbai, Maharashtra

3 Department of Radiodiagnosis, Tata Memorial Centre, Mumbai, Maharashtra

*Corresponding author: Dr. Kumar Prabhash. kprabhash1@gmail.com

Published: 2020-12-21

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Introduction: Nonclear cell (NCC) metastatic renal cell carcinoma (mRCC) is a biologically heterogeneous entity. We report the outcomes of NCC mRCC treated with first-line vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin (mTOR) inhibitors at our institute. This is first such report from India. Methods: This is a retrospective analysis of the 40 consecutive patients of NCC mRCC treated between January 2013 and June 2015 in routine clinical practice at our institute. The primary endpoint analyzed was overall survival (OS) with respect to the type of first-line treatment and tumor histology. Results: The most common histological subtype was papillary in 25 patients (62.5%) followed by sarcomatoid in six (15%), chromophobe in 5 (12.5%), translocation-associated in one patient, and other nonspecified in three patients. First-line treatment was sorafenib in 14 (35%), sunitinib in 9 (22.5%), pazopanib in 8 (20%), everolimus in seven (17.5%), and best-supportive care (BSC) in two (5%) patients. Partial response, stable disease, and progression was observed in six (15%), 13 (32.5%), and nine (22.5%) cases, respectively, as the best response to first-line treatment. The median OS was 11.7 months and median event-free survival was 6.1 months in the whole cohort. The median OS in months for different first-line treatments were as follows: sorafenib (16.2), sunitinib (11.7), pazopanib (not reached, mean-23.9 ± 6.0), everolimus (4.1) and BSC (0.6) and for different histological subtypes were as follows: papillary (9.8), chromophobe (not reached, mean-30.3 ± 8.4), sarcomatoid (4.1), and others (7.9). Conclusions: Chromophobe histology has a better outcome compared to other histological subtypes, and anti-VEGF tyrosine kinase inhibitors are preferable first-line agents compared to mTOR inhibitors.

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References

Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005;353:2477-90.
Zisman A, Chao DH, Pantuck AJ, Kim HJ, Wieder JA, Figlin RA, et al. Unclassified renal cell carcinoma: Clinical features and prognostic impact of a new histological subtype. J Urol 2002;168:950-5.
Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: Renal, penile, and testicular tumours. Eur Urol 2016;70:93-105.
Pal SK, Choueiri TK. Systemic therapies for metastatic renal cell carcinoma of variant histology. In: Tannir NM, editor. Renal Cell Carcinoma. 1st ed. Newyork: Oxford American Oncology Library; 2014. p. 109-16.
Sankin A, Hakimi AA, Hsieh JJ, Molina AM. Metastatic non-clear cell renal cell carcinoma: An evidence based review of current treatment strategies. Front Oncol 2015;5:67.
Vera-Badillo FE, Templeton AJ, Duran I, Ocana A, de Gouveia P, Aneja P, et al. Systemic therapy for non-clear cell renal cell carcinomas: A systematic review and meta-analysis. Eur Urol 2015;67:740-9.
Kroeger N, Xie W, Lee JL, Bjarnason GA, Knox JJ, Mackenzie MJ, et al. Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: Characterization of survival outcome and application of the International mRCC database consortium criteria. Cancer 2013;119:2999-3006.
Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): A multicentre, open-label, randomised phase 2 trial. Lancet Oncol 2016;17:378-88.
Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 2014;32:2765-72.
Tannir NM, Jonasch E, Albiges L, Altinmakas E, Ng CS, Matin SF, et al. Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): A randomized multicenter phase 2 trial. Eur Urol 2016;69:866-74.
Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81.
Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, et al. Aphase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Eur Urol 2012;62:1013-9.
Lee JL, Ahn JH, Lim HY, Park SH, Lee SH, Kim TM, et al. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Ann Oncol 2012;23:2108-14.
Molina AM, Feldman DR, Ginsberg MS, Kroog G, Tickoo SK, Jia X, et al. Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma. Invest New Drugs 2012;30:335-40.
Koh Y, Lim HY, Ahn JH, Lee JL, Rha SY, Kim YJ, et al. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Ann Oncol 2013;24:1026-31.
Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr., et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 2010;116:1272-80.
Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: An expanded-access trial. Lancet Oncol 2009;10:757-63.
Paglino C, Imarisio I, Ganini C, Morbini P, Vercelli A, Bregant C, et al. Sunitinib in advanced metastatic non-clear cell renal cell carcinoma: A single institution retrospective study. Future Oncol 2012;8:1605-12.
Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 2008;26:127-31.
Matrana MR, Baiomy A, Campbell M, Alamri S, Shetty A, Teegavarapu P, et al. Outcomes of patients with metastatic non-clear-cell renal cell carcinoma treated with pazopanib. Clin Genitourin Cancer 2017;15:e205-8.
Stadler WM, Figlin RA, Ernstoff MS, Curti B, Pendergrass K, Srinivas S, et al. The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial. Safety and efficacy in patients (pts) with non-clear cell (NCC) renal cell carcinoma (RCC). J Clin Oncol 2007;25:5036.
Delahunt B, Eble JN. Papillary renal cell carcinoma: A clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 1997;10:537-44.
Yang XJ, Tan MH, Kim HL, Ditlev JA, Betten MW, Png CE, et al. Amolecular classification of papillary renal cell carcinoma. Cancer Res 2005;65:5628-37.
Mejean A, Hopirtean V, Bazin JP, Larousserie F, Benoit H, Chrétien Y, et al. Prognostic factors for the survival of patients with papillary renal cell carcinoma: Meaning of histological typing and multifocality. J Urol 2003;170:764-7.
Ravaud A, Oudard S, De Fromont M, Chevreau C, Gravis G, Zanetta S, et al. First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: A phase II study (SUPAP) by the French Genitourinary Group (GETUG)†. Ann Oncol 2015;26:1123-8.
Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, et al. Final results of the European advanced renal cell carcinoma sorafenib (EU-ARCCS) expanded-access study: A large open-label study in diverse community settings. Ann Oncol 2011;22:1812-23.
Mian BM, Bhadkamkar N, Slaton JW, Pisters PW, Daliani D, Swanson DA, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol 2002;167:65-70.
Nanus DM, Garino A, Milowsky MI, Larkin M, Dutcher JP. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer 2004;101:1545-51.

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[1] Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005;353:2477-90.

[2] Zisman A, Chao DH, Pantuck AJ, Kim HJ, Wieder JA, Figlin RA, et al. Unclassified renal cell carcinoma: Clinical features and prognostic impact of a new histological subtype. J Urol 2002;168:950-5.

[3] Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: Renal, penile, and testicular tumours. Eur Urol 2016;70:93-105.

[4] Pal SK, Choueiri TK. Systemic therapies for metastatic renal cell carcinoma of variant histology. In: Tannir NM, editor. Renal Cell Carcinoma. 1st ed. Newyork: Oxford American Oncology Library; 2014. p. 109-16.

[5] Sankin A, Hakimi AA, Hsieh JJ, Molina AM. Metastatic non-clear cell renal cell carcinoma: An evidence based review of current treatment strategies. Front Oncol 2015;5:67.

[6] Vera-Badillo FE, Templeton AJ, Duran I, Ocana A, de Gouveia P, Aneja P, et al. Systemic therapy for non-clear cell renal cell carcinomas: A systematic review and meta-analysis. Eur Urol 2015;67:740-9.

[7] Kroeger N, Xie W, Lee JL, Bjarnason GA, Knox JJ, Mackenzie MJ, et al. Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: Characterization of survival outcome and application of the International mRCC database consortium criteria. Cancer 2013;119:2999-3006.

[8] Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): A multicentre, open-label, randomised phase 2 trial. Lancet Oncol 2016;17:378-88.

[9] Motzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 2014;32:2765-72.

[10] Tannir NM, Jonasch E, Albiges L, Altinmakas E, Ng CS, Matin SF, et al. Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): A randomized multicenter phase 2 trial. Eur Urol 2016;69:866-74.

[11] Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81.

[12] Tannir NM, Plimack E, Ng C, Tamboli P, Bekele NB, Xiao L, et al. Aphase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Eur Urol 2012;62:1013-9.

[13] Lee JL, Ahn JH, Lim HY, Park SH, Lee SH, Kim TM, et al. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Ann Oncol 2012;23:2108-14.

[14] Molina AM, Feldman DR, Ginsberg MS, Kroog G, Tickoo SK, Jia X, et al. Phase II trial of sunitinib in patients with metastatic non-clear cell renal cell carcinoma. Invest New Drugs 2012;30:335-40.

[15] Koh Y, Lim HY, Ahn JH, Lee JL, Rha SY, Kim YJ, et al. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Ann Oncol 2013;24:1026-31.

[16] Stadler WM, Figlin RA, McDermott DF, Dutcher JP, Knox JJ, Miller WH Jr., et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 2010;116:1272-80.

[17] Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: An expanded-access trial. Lancet Oncol 2009;10:757-63.

[18] Paglino C, Imarisio I, Ganini C, Morbini P, Vercelli A, Bregant C, et al. Sunitinib in advanced metastatic non-clear cell renal cell carcinoma: A single institution retrospective study. Future Oncol 2012;8:1605-12.

[19] Choueiri TK, Plantade A, Elson P, Negrier S, Ravaud A, Oudard S, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 2008;26:127-31.

[20] Matrana MR, Baiomy A, Campbell M, Alamri S, Shetty A, Teegavarapu P, et al. Outcomes of patients with metastatic non-clear-cell renal cell carcinoma treated with pazopanib. Clin Genitourin Cancer 2017;15:e205-8.

[21] Stadler WM, Figlin RA, Ernstoff MS, Curti B, Pendergrass K, Srinivas S, et al. The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial. Safety and efficacy in patients (pts) with non-clear cell (NCC) renal cell carcinoma (RCC). J Clin Oncol 2007;25:5036.

[22] Delahunt B, Eble JN. Papillary renal cell carcinoma: A clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 1997;10:537-44.

[23] Yang XJ, Tan MH, Kim HL, Ditlev JA, Betten MW, Png CE, et al. Amolecular classification of papillary renal cell carcinoma. Cancer Res 2005;65:5628-37.

[24] Mejean A, Hopirtean V, Bazin JP, Larousserie F, Benoit H, Chrétien Y, et al. Prognostic factors for the survival of patients with papillary renal cell carcinoma: Meaning of histological typing and multifocality. J Urol 2003;170:764-7.

[25] Ravaud A, Oudard S, De Fromont M, Chevreau C, Gravis G, Zanetta S, et al. First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: A phase II study (SUPAP) by the French Genitourinary Group (GETUG)†. Ann Oncol 2015;26:1123-8.

[26] Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, et al. Final results of the European advanced renal cell carcinoma sorafenib (EU-ARCCS) expanded-access study: A large open-label study in diverse community settings. Ann Oncol 2011;22:1812-23.

[27] Mian BM, Bhadkamkar N, Slaton JW, Pisters PW, Daliani D, Swanson DA, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol 2002;167:65-70.

[28] Nanus DM, Garino A, Milowsky MI, Larkin M, Dutcher JP. Active chemotherapy for sarcomatoid and rapidly progressing renal cell carcinoma. Cancer 2004;101:1545-51.

Treatment outcomes of metastatic nonclear cell renal cell carcinoma: A single institution retrospective analysis

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Abstract

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