Prognostic ability of early tumor shrinkage on overall survival (OS) in metastatic renal cell carcinoma (mRCC) – a validation study

Abstract

Background: Early tumor shrinkage (eTS) of 10% has been identified as a putative prognostic marker in mRCC, which could serve as an early read-out in clinical trials. We aimed to validate the prognostic role of eTS in first line TKI treatment using data from the COMPARZ study (NCT00720941). Methods: A retrospective analysis on data of 1100 1st line patients treated with sunitinib or pazopanib was performed. Tumor response was measured according to RECIST 1.1. eTS was a priori defined as tumor shrinkage by >10%. The Kaplan-Meier method was used to estimate time-to-event outcomes. A landmark analysis was performed on day (d) 42 and d 90 after randomization. Cox proportional hazards regression was performed to evaluate the effect of prognostic factors on overall survival after d 42 and d 90. Results: At d 42 and 90, 582 and 1007 patients were evaluable for landmark analysis, of whom 56.5% and 65.2% achieved eTS, respectively. In patients with eTS median OS was 34.1 (CI95% 28.4; not reached(NR)) and 33.6 (CI95% 30.1; NR) mo. at d 42 and d 90, respectively, compared to 19.6 (CI95% 14.0; 28.9) and 15.1 (CI95% 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). In multivariable analyses, adjusted for age, sex, performance status, nephrectomy, anemia, neutrophils, platelets, LDH, organs involved, liver metastases, time from diagnosis, calcium, treatment, and baseline tumor burden, eTS >10% remained an independent prognostic marker of OS for both d 42: HR 0.53 (0.41; 0.69), p 10% has prognostic relevance in mRCC and reflects a valid early endpoint in clinical trials. (Table Presented).