Early tumor shrinkage is independently associated with improved overall survival among patients with metastatic renal cell carcinoma: a validation study using the COMPARZ cohort
- 150 Downloads
Early tumor shrinkage (eTS) has prognostic value in metastatic renal cell carcinoma (mRCC). We aimed to validate the role of eTS in first line treatment from the COMPARZ study (NCT00720941).
1100 patients treated with sunitinib or pazopanib were analyzed for tumor response according to RECIST 1.0. eTS was defined as tumor shrinkage by ≥ 10%. A landmark analysis was performed on day (d) 42 and 90 and Cox proportional hazards regression was computed for the prognostic effect of eTS.
In patients with eTS median OS was 34.1 [CI 95% 28.4; not reached (NR)] and 33.6 (CI 95% 30.1; NR) months (mo) at d 42 and 90, respectively, compared to 19.6 (CI 95% 14.0; 28.9) and 15.1 (CI 95% 12.4; 18.7) mo for patients without eTS. There was no interaction between type of treatment and eTS (d 42 p = 0.79; d 90 p = 0.37). eTS ≥ 10% remained an independent prognostic marker in multivariable analyses at both d 42 and 90.
Similar results were found for eTS at the 42 and 90 days landmarks. eTS ≥ 10% has prognostic relevance in mRCC and reflects a putative tool to guide future clinical treatment.
KeywordsEarly tumor shrinkage Overall survival Predictive factor Prognostic factor Progression-free survival Metastatic renal cell carcinoma
The authors thank the patients and investigators who participated in the COMPARZ trial used for this analysis.
VG had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: VG, GP. Acquisition of data: VG, MD, GP. Analysis and interpretation of data: VG, MD, GP. Drafting of the manuscript: VG. Critical revision of the manuscript for important intellectual content: VG, MD, GP. Statistical analysis: GP. Administrative, technical, or material support: Not applicable. Supervision: VG.
Compliance with ethical standards
The study sponsor (Novartis) shared access to the primary data of the COMPARZ study but was not involved in concept, design, conduct, or analysis of the data. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
Viktor Grünwald has an advisory role at Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Eisai, Roche and has received honoraria from Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Eisai and Roche. Marion Dietrich and Gregory Pond do not have any conflict of interest.
- 4.Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T et al (2015) Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol 16:1473–1482. https://doi.org/10.1016/S1470-2045(15)00290-9 CrossRefPubMedGoogle Scholar
- 9.Powles T, Staehler M, Ljungberg B, Bensalah K, Canfield SE, Dabestani S et al (2016) European association of urology guidelines for clear cell renal cancers that are resistant to vascular endothelial growth factor receptor-targeted therapy. Eur Urol. https://doi.org/10.1016/j.eururo.2016.06.009 PubMedCentralGoogle Scholar
- 13.Collinson FJ, Gregory WM, McCabe C, Howard H, Lowe C, Potrata D et al (2012) The STAR trial protocol: a randomised multi-stage phase II/III study of sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic renal cancer. BMC Cancer 12:598. https://doi.org/10.1186/1471-2407-12-598 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Abel EJ, Culp SH, Tannir NM, Tamboli P, Matin SF, Wood CG (2011) Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol 60:1–7. https://doi.org/10.1016/j.eururo.2011.07.008 CrossRefGoogle Scholar
- 15.Krajewski KM, Guo M, van den Abbeele AD, Yap J, Ramaiya N, Jagannathan J et al (2011) Comparison of four early post therapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol 59:856–862. https://doi.org/10.1016/j.eururo.2011.01.038 CrossRefPubMedGoogle Scholar
- 16.Busch J, Seidel C, Goranova I, Erber B, Peters R, Friedersdorff F et al (2014) Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma. Eur J Cancer 50:563–569. https://doi.org/10.1016/j.ejca.2013.10.017 CrossRefPubMedGoogle Scholar
- 17.Motzer RJ, Sharma P, Escudier BJ, McDermott DF, George S, Srinivas S et al (2016) Correlation of response with overall survival (OS) for nivolumab vs everolimus in advanced renal cell carcinoma (aRCC): results from the phase III CheckMate 025 study. J Clin Oncol 34:4552. https://doi.org/10.1200/JCO.2016.34.15_suppl.4552 CrossRefGoogle Scholar
- 18.McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC et al (2015) Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J Clin Oncol 33:2013–2020. https://doi.org/10.1200/JCO.2014.58.1041 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Krajewski KM, Nishino M, Ramaiya NH, Choueiri TK (2015) RECIST 1.1 compared with RECIST 1.0 in patients with advanced renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. AJR Am J Roentgenol 204:W282–W288. https://doi.org/10.2214/AJR.14.13236 CrossRefPubMedPubMedCentralGoogle Scholar