Comparison of axitinib and sunitinib as first-line therapies for metastatic renal cell carcinoma: a real-world multicenter analysis
- 203 Downloads
We aimed to compare oncological outcomes and safety of axitinib and sunitinib in patients with treatment-naïve metastatic renal cell carcinoma (mRCC). We retrospectively evaluated 169 patients with mRCC who were treated with axitinib or sunitinib as the first-line therapy in five hospitals between October 2008 and August 2018. Oncological outcomes and safety were compared between axitinib (n = 68) and sunitinib (n = 101) groups. Inverse probability of treatment weighted (IPTW)-adjusted Cox regression analysis was performed to evaluate effects of first-line therapies on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Patients in the axitinib group were significantly older (66 vs. 72 years) than those in the sunitinib group. Median relative dose intensity was significantly higher in the axitinib group (94 ± 62%) than in the sunitinib group (65 ± 20%; P = 0.001). Objective response rate was significantly higher in the axitinib group (21%) than in the sunitinib group (10%; P = 0.042). IPTW-adjusted Cox regression analysis revealed significant differences in CSS and OS but not in PFS between the two groups. Safety in terms of grade ≥ 3 adverse events was significantly different between the axitinib (34%) and sunitinib (55%) groups (P = 0.006). Compared with sunitinib, axitinib significantly prolonged CSS and OS and showed a safer profile as the first-line therapy for treatment-naïve mRCC.
KeywordsAxitinib Sunitinib Metastatic renal cell carcinoma First-line therapy Safety Efficacy
Metastatic renal cell carcinoma
Tyrosine kinase inhibitors
Vascular endothelial growth factor
- ECOG PS
Eastern Cooperative Oncology Group performance status
International Metastatic Renal Cell Carcinoma Database Consortium
Inverse probability of treatment weighted
- 95% CI
95% confidence interval
Relative dose intensity
Mammalian target of rapamycin inhibitor
The authors would like to thank Takuma Narita, Teppei Okamoto, Itsuto Hamano, Hirotaka Horiguchi, Masaaki Oikawa, Daisuke Noro, Kazuhisa Hagiwara, Yuki Fujita, Yukie Nishizawa, and Satomi Sakamoto for their invaluable support in data collection. The authors would also like to thank Enago (http://www.enago.jp) for English language review.
This work was supported by a Grant-in-Aid for Scientific Research (Nos. 17K11118, 17K11119, 17K16768, 17K16770, 17K167711, 18K16681, 18K16682, 18K16717, 18K16718, 18K16719, and 18K09157) from the Japan Society for the Promotion of Science.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest.
- 1.Hutson TE, Lesovoy V, Al-Shukri S, Stus VP, Lipatov ON, Bair AH, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14(13):1287–94. https://doi.org/10.1016/s1470-2045(13)70465-0.CrossRefPubMedGoogle Scholar
- 2.Hutson TE, Al-Shukri S, Stus VP, Lipatov ON, Shparyk Y, Bair AH, et al. Axitinib versus sorafenib in first-line metastatic renal cell carcinoma: overall survival from a randomized phase III trial. Clin Genitourin Cancer. 2017;15(1):72–6. https://doi.org/10.1016/j.clgc.2016.05.008.CrossRefPubMedGoogle Scholar
- 3.Pal SK, Signorovitch JE, Li N, Zichlin ML, Liu Z, Ghate SR, et al. Patterns of care among patients receiving sequential targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the USA. Int J Urol. 2017;24(4):272–8. https://doi.org/10.1111/iju.13314.CrossRefPubMedGoogle Scholar
- 6.Lee JL, Kim MK, Park I, Ahn JH, Lee DH, Ryoo HM, et al. RandomizEd phase II trial of sunitinib four weeks on and two weeks off versus two weeks on and one week off in metastatic clear-cell type REnal cell carcinoma: restore trial. Ann Oncol. 2015;26(11):2300–5. https://doi.org/10.1093/annonc/mdv357.CrossRefPubMedGoogle Scholar
- 7.Iwamoto K, Ishihara H, Takagi T, Kondo T, Yoshida K, Iizuka J, et al. Evaluation of relative dose intensity during the early phase of first-line sunitinib treatment using a 2-week-on/1-week-off regimen for metastatic renal cell carcinoma. Med Oncol. 2018;35(6):78. https://doi.org/10.1007/s12032-018-1139-y.CrossRefPubMedGoogle Scholar
- 9.Mouillet G, Paillard MJ, Maurina T, Vernerey D, Nguyen Tan Hon T, Almotlak H, et al. Open-label, randomized multicentre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma: study protocol of the SURF trial. Trials. 2018;19(1):221. https://doi.org/10.1186/s13063-018-2613-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Kondo T, Takagi T, Kobayashi H, Iizuka J, Nozaki T, Hashimoto Y, et al. Superior tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-week-off in patients with metastatic renal cell carcinoma–comparison to standard dosing schedule of 4-weeks-on and 2-weeks-off. Jpn J Clin Oncol. 2014;44(3):270–7. https://doi.org/10.1093/jjco/hyt232.CrossRefPubMedGoogle Scholar
- 12.Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9. https://doi.org/10.1016/s0140-6736(11)61613-9.CrossRefPubMedGoogle Scholar
- 14.Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmuller C, et al. SWITCH: a randomised, sequential, open-label study to evaluate the efficacy and safety of sorafenib-sunitinib versus sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015;68(5):837–47. https://doi.org/10.1016/j.eururo.2015.04.017.CrossRefPubMedGoogle Scholar
- 15.Oya M, Tomita Y, Fukasawa S, Shinohara N, Habuchi T, Rini BI, et al. Overall survival of first-line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study. Cancer Sci. 2017;108(6):1231–9. https://doi.org/10.1111/cas.13232.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Horiguchi H, Yoneyama T, Hatakeyama S, Tokui N, Sato T, Fujita N, et al. Impact of bacillus Calmette-Guerin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy. Med Oncol. 2018;35(4):41. https://doi.org/10.1007/s12032-018-1102-y.CrossRefPubMedGoogle Scholar
- 18.Momota M, Hatakeyama S, Tokui N, Sato T, Yamamoto H, Tobisawa Y, et al. The impact of preoperative severe renal insufficiency on poor postsurgical oncological prognosis in patients with urothelial carcinoma. Eur Urol Focus. 2018. https://doi.org/10.1016/j.euf.2018.03.003.CrossRefPubMedGoogle Scholar
- 19.Hamano I, Hatakeyama S, Iwamurau H, Fujita N, Fukushi K, Narita T, et al. Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer. Oncotarget. 2017;8(37):61404–14. https://doi.org/10.18632/oncotarget.18248.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Hosogoe S, Hatakeyama S, Kusaka A, Hamano I, Iwamura H, Fujita N, et al. Platinum-based neoadjuvant chemotherapy improves oncological outcomes in patients with locally advanced upper tract urothelial carcinoma. Eur Urol Focus. 2017:231–40. https://doi.org/10.1016/j.euf.2017.03.013.
- 21.Kodama H, Hatakeyama S, Fujita N, Iwamura H, Anan G, Fukushi K, et al. Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. Oncotarget. 2017;8(47):83183–94. https://doi.org/10.18632/oncotarget.20554.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Kubota Y, Hatakeyama S, Tanaka T, Fujita N, Iwamura H, Mikami J, et al. Oncological outcomes of neoadjuvant chemotherapy in patients with locally advanced upper tract urothelial carcinoma: a multicenter study. Oncotarget. 2017;8(60):101500–8. https://doi.org/10.18632/oncotarget.21551.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Kusaka A, Hatakeyama S, Hosogoe S, Hamano I, Iwamura H, Fujita N, et al. Detecting asymptomatic recurrence after radical cystectomy contributes to better prognosis in patients with muscle-invasive bladder cancer. Med Oncol. 2017;34(5):90. https://doi.org/10.1007/s12032-017-0955-9.CrossRefPubMedGoogle Scholar
- 25.Koie T, Ohyama C, Yoneyama T, Yamamoto H, Imai A, Hatakeyama S, et al. Feasibly of axitinib as first-line therapy for advanced or metastatic renal cell carcinoma: a single-institution experience in Japan. BMC Urol. 2015;15:32. https://doi.org/10.1186/s12894-015-0027-4.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Tanaka Y, Hatakeyama S, Hosogoe S, Tanaka T, Hamano I, Kusaka A, et al. Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava. Int J Clin Oncol. 2018;23(1):134–41. https://doi.org/10.1007/s10147-017-1169-z.CrossRefPubMedGoogle Scholar
- 28.Hosogoe S, Hatakeyama S, Kusaka A, Hamano I, Tanaka Y, Hagiwara K, et al. Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma. Oncotarget. 2017. https://doi.org/10.18632/oncotarget.17930.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018;19(4):451–60. https://doi.org/10.1016/s1470-2045(18)30107-4.CrossRefPubMedGoogle Scholar