Optimal Sequencing of the First- and Second-line Target Therapies in Metastatic Renal Cell Carcinoma: Based on Nationally Representative Data Analysis from the Korean National Health Insurance System

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2023 May 30

PMID 37254112

Authors

Dong Hyuk Kang

Joo Yong Lee

Yunhee Lee

U-Syn Ha

Affiliations

Soon will be listed here.

Abstract

Background: The authors intend to compare the effects of each targeted therapy (TT) in the treatment of patients with metastatic renal cell carcinoma (mRCC) using big data based on the Korean National Health Insurance System (NHIS) and determine the optimal treatment sequence.

Methods: Data on the medical use of patients with kidney cancer were obtained from the NHIS database from January 1, 2002, to December 31, 2020. Patient variables included age, sex, income level, place of residence, prescribing department, and duration from diagnosis to the prescription date. The primary outcome was overall survival (OS) for each drug and sequencing. We performed propensity score matching (PSM) according to age, sex, and Charlson Comorbidity Index based on the primary TTs.

Results: After 1:1 PSM, the sunitinib (SUN) (n = 1,214) and pazopanib (PAZ) (n = 1,214) groups showed a well-matched distribution across the entire cohort. In the primary treatment group, PAZ had lower OS than SUN (HR, 1.167; p = 0.0015). In the secondary treatment group, axitinib (AXI) had more favorable OS than cabozantinib (CAB) (HR, 0.735; p = 0.0118), and everolimus had more adverse outcomes than CAB (HR, 1.544; p < 0.0001). In the first to second TT sequencing, SUN-AXI had the highest OS; however, there was no statistically significant difference when compared with PAZ-AXI, which was the second highest (HR, 0.876; p = 0.3312). The 5-year survival rate was calculated in the following order: SUN-AXI (51.44%), PAZ-AXI (47.12%), SUN-CAB (43.59%), and PAZ-CAB (34.28%). When the four sequencing methods were compared, only SUN-AXI versus PAZ-CAB (p = 0.003) and PAZ-AXI versus PAZ-CAB (p = 0.017) were statistically significant.

Conclusions: In a population-based RWD analysis of Korean patients with mRCC, SUN-AXI sequencing was shown to be the most effective among the first to second TT sequencing methods in treatment, with a relative survival advantage over other sequencing combinations. To further support the results of this study, risk-stratified analysis is needed.

Citing Articles

Axitinib after Treatment Failure with Sunitinib or Cytokines in Advanced Renal Cell Carcinoma-Systematic Literature Review of Clinical and Real-World Evidence.

Sharma A, Bahl A, Frazer R, Godhania E, Halfpenny N, Hartl K Cancers (Basel). 2024; 16(15).

PMID: 39123435 PMC: 11312084. DOI: 10.3390/cancers16152706.

References

Deng H, Huang Y, Hong Z, Yuan X, Cao Z, Wei Y . Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis. BMC Cancer. 2019; 19(1):489. PMC: 6533682. DOI: 10.1186/s12885-019-5704-3. View

Cho I, Chung J . Current status of targeted therapy for advanced renal cell carcinoma. Korean J Urol. 2012; 53(4):217-28. PMC: 3332131. DOI: 10.4111/kju.2012.53.4.217. View

Escudier B, Sharma P, Mcdermott D, George S, Hammers H, Srinivas S . CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma. Eur Urol. 2017; 72(6):962-971. DOI: 10.1016/j.eururo.2017.02.010. View

Motzer R, Tannir N, Mcdermott D, Frontera O, Melichar B, Choueiri T . Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018; 378(14):1277-1290. PMC: 5972549. DOI: 10.1056/NEJMoa1712126. View

Geczi L, Bodoky G, Rokszin G, Fabian I, Torday L . Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma. Pathol Oncol Res. 2020; 26(4):2201-2207. PMC: 7471136. DOI: 10.1007/s12253-020-00809-z. View

Eichelberg C, Vervenne W, De Santis M, Fischer von Weikersthal L, Goebell P, Lerchenmuller C . 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. DOI: 10.1016/j.eururo.2015.04.017. View

Swift B, Jain L, White C, Chandrasekaran V, Bhandari A, Hughes D . Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care. Clin Transl Sci. 2018; 11(5):450-460. PMC: 6132367. DOI: 10.1111/cts.12559. View

Kim S, Park W, Kim S, Joung J, Seo H, Lee K . Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy. Cancer Res Treat. 2016; 48(3):1092-101. PMC: 4946361. DOI: 10.4143/crt.2015.316. View

Rini B, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson T . Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011; 378(9807):1931-9. DOI: 10.1016/S0140-6736(11)61613-9. View

10.

Racsa P, Whisman T, Worley K . Comparing two tyrosine kinase inhibitors for treatment of advanced renal cell carcinoma in Medicare and commercially insured patients. Curr Med Res Opin. 2015; 31(10):1933-40. DOI: 10.1185/03007995.2015.1081881. View

11.

Hutson T, Escudier B, Esteban E, Bjarnason G, Lim H, Pittman K . Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2013; 32(8):760-7. PMC: 5569683. DOI: 10.1200/JCO.2013.50.3961. View

12.

Choueiri T, Escudier B, Powles T, Mainwaring P, Rini B, Donskov F . Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1814-23. PMC: 5024539. DOI: 10.1056/NEJMoa1510016. View

13.

Ljungberg B, Alamdari F, Rasmuson T, Roos G . Follow-up guidelines for nonmetastatic renal cell carcinoma based on the occurrence of metastases after radical nephrectomy. BJU Int. 1999; 84(4):405-11. DOI: 10.1046/j.1464-410x.1999.00202.x. View

14.

Proskorovsky I, Benedict A, Negrier S, Bargo D, Sandin R, Ramaswamy K . Axitinib, cabozantinib, or everolimus in the treatment of prior sunitinib-treated patients with metastatic renal cell carcinoma: results of matching-adjusted indirect comparison analyses. BMC Cancer. 2018; 18(1):1271. PMC: 6300002. DOI: 10.1186/s12885-018-5157-0. View

15.

Kim D, Park J, Yang W, Doo S, Kim J, Song Y . Changes in diagnosis rate and treatment trends of benign prostatic hyperplasia in Korea: A nationwide population-based cohort study. Prostate Int. 2022; 9(4):215-220. PMC: 8740390. DOI: 10.1016/j.prnil.2021.08.002. View

16.

Motzer R, Hutson T, Cella D, Reeves J, Hawkins R, Guo J . Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013; 369(8):722-31. DOI: 10.1056/NEJMoa1303989. View

17.

Motzer R, Jonasch E, Agarwal N, Alva A, Baine M, Beckermann K . Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20(1):71-90. PMC: 10191161. DOI: 10.6004/jnccn.2022.0001. View

18.

Joung J, Lim J, Oh C, Jung K, Cho H, Kim S . Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea. Cancer Res Treat. 2016; 49(3):607-615. PMC: 5512381. DOI: 10.4143/crt.2016.139. View

19.

Khosla S, White R, Medina J, Ouwens M, Emmas C, Koder T . Real world evidence (RWE) - a disruptive innovation or the quiet evolution of medical evidence generation?. F1000Res. 2018; 7:111. PMC: 6039945. DOI: 10.12688/f1000research.13585.2. View

20.

Facchini G, Rossetti S, Berretta M, Cavaliere C, Scagliarini S, Vitale M . Second line therapy with axitinib after only prior sunitinib in metastatic renal cell cancer: Italian multicenter real world SAX study final results. J Transl Med. 2019; 17(1):296. PMC: 6716812. DOI: 10.1186/s12967-019-2047-4. View