Viktor Grünwald1, Xun Lin2, Daniel Kalanovic3, Ronit Simantov4. 1. Hannover Medical School, Hannover, Germany. Electronic address: Gruenwald.Viktor@mh-hannover.de. 2. Pfizer Oncology, La Jolla, CA, USA. 3. Pfizer Oncology, Berlin, Germany. 4. Pfizer Oncology, New York, NY, USA.
Abstract
BACKGROUND: The predictive role of objective remission remains undefined for targeted agents in metastatic renal cell carcinoma (mRCC); however, early tumour shrinkage (eTS) was shown to be predictive and/or prognostic for overall survival (OS) and progression-free survival (PFS) in mRCC in several small studies. OBJECTIVE: To evaluate the degree of eTS following systemic therapy that may predict survival in mRCC. DESIGN, SETTING, AND PARTICIPANTS: Data from 4334 patients with mRCC in phase 2 and 3 clinical trials between 2003 and 2013 were pooled for analyses. Early tumour shrinkage was assessed based on percentage change in sum of the longest diameters of target lesions at first postbaseline scan. Patients were categorised by a more or equal versus less optimal threshold of eTS, assessed using receiver operating characteristic (ROC) analysis. OS and PFS in patients with eTS were summarised using the Kaplan-Meier method. INTERVENTION: Axitinib, bevacizumab, interferon α, sorafenib, sunitinib, or temsirolimus. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured optimal thresholds of eTS and eTS as a predictor of OS or PFS. RESULTS AND LIMITATIONS: Optimal threshold of eTS for the prediction of OS and PFS was determined to be approximately 10%. In Cox proportional hazards models, compared with patients without eTS, those with eTS had significantly longer OS (hazard ratio [HR]: 0.615; p<0.0001; median: 28.5 vs 16.0 mo) and PFS (HR: 0.628; p<0.0001; median: 10.5 vs 5.3 mo). The major limitation was the retrospective nature of our analysis, including different lines and types of therapy, although subset analyses detected a similar predictive pattern for eTS across all lines and types of therapy. CONCLUSIONS: Early tumour shrinkage ≥10% at first postbaseline assessment could serve as a putative early end point in patients with mRCC. A prospective evaluation of eTS in clinical trials is warranted. PATIENT SUMMARY: Early tumour shrinkage may be used to identify patients with metastatic renal cell carcinoma who would benefit from treatment with antitumour agents. TRIAL REGISTRATION: The clinical trials are registered on ClinicalTrials.gov (NCT00267748, NCT00338884, NCT00835978, NCT00065468, NCT00083889, NCT00631371, NCT00920816, NCT00077974, NCT00137423, NCT00054886, NCT00678392, and NCT00474786).
BACKGROUND: The predictive role of objective remission remains undefined for targeted agents in metastatic renal cell carcinoma (mRCC); however, early tumour shrinkage (eTS) was shown to be predictive and/or prognostic for overall survival (OS) and progression-free survival (PFS) in mRCC in several small studies. OBJECTIVE: To evaluate the degree of eTS following systemic therapy that may predict survival in mRCC. DESIGN, SETTING, AND PARTICIPANTS: Data from 4334 patients with mRCC in phase 2 and 3 clinical trials between 2003 and 2013 were pooled for analyses. Early tumour shrinkage was assessed based on percentage change in sum of the longest diameters of target lesions at first postbaseline scan. Patients were categorised by a more or equal versus less optimal threshold of eTS, assessed using receiver operating characteristic (ROC) analysis. OS and PFS in patients with eTS were summarised using the Kaplan-Meier method. INTERVENTION: Axitinib, bevacizumab, interferon α, sorafenib, sunitinib, or temsirolimus. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured optimal thresholds of eTS and eTS as a predictor of OS or PFS. RESULTS AND LIMITATIONS: Optimal threshold of eTS for the prediction of OS and PFS was determined to be approximately 10%. In Cox proportional hazards models, compared with patients without eTS, those with eTS had significantly longer OS (hazard ratio [HR]: 0.615; p<0.0001; median: 28.5 vs 16.0 mo) and PFS (HR: 0.628; p<0.0001; median: 10.5 vs 5.3 mo). The major limitation was the retrospective nature of our analysis, including different lines and types of therapy, although subset analyses detected a similar predictive pattern for eTS across all lines and types of therapy. CONCLUSIONS: Early tumour shrinkage ≥10% at first postbaseline assessment could serve as a putative early end point in patients with mRCC. A prospective evaluation of eTS in clinical trials is warranted. PATIENT SUMMARY: Early tumour shrinkage may be used to identify patients with metastatic renal cell carcinoma who would benefit from treatment with antitumour agents. TRIAL REGISTRATION: The clinical trials are registered on ClinicalTrials.gov (NCT00267748, NCT00338884, NCT00835978, NCT00065468, NCT00083889, NCT00631371, NCT00920816, NCT00077974, NCT00137423, NCT00054886, NCT00678392, and NCT00474786).
Authors: Nizar M Tannir; Robert A Figlin; Martin E Gore; M Dror Michaelson; Robert J Motzer; Camillo Porta; Brian I Rini; Caroline Hoang; Xun Lin; Bernard Escudier Journal: Clin Genitourin Cancer Date: 2017-06-20 Impact factor: 2.872
Authors: Brian I Rini; Victor Gruenwald; Eric Jonasch; Mayer N Fishman; Yoshihiko Tomita; M Dror Michaelson; Jamal Tarazi; Laura Cisar; Subramanian Hariharan; Angel H Bair; Brad Rosbrook; Thomas E Hutson Journal: Target Oncol Date: 2017-06 Impact factor: 4.493
Authors: Elena García-Martínez; Melody Smith; Aitziber Buqué; Fernando Aranda; Francisco Ayala de la Peña; Alejandra Ivars; Manuel Sanchez Cánovas; Ma Angeles Vicente Conesa; Jitka Fucikova; Radek Spisek; Laurence Zitvogel; Guido Kroemer; Lorenzo Galluzzi Journal: Oncoimmunology Date: 2018-02-15 Impact factor: 8.110