RECIST 1.1 for Response Evaluation Apply Not Only to Chemotherapy-Treated Patients But Also to Targeted Cancer Agents: A Pooled Database Analysis

Saskia Litière, Gaëlle Isaac, Elisabeth G. E. de Vries, Jan Bogaerts, Alice Chen, Janet Dancey, Robert Ford, Stephen Gwyther, Otto Hoekstra, Erich Huang, Nancy Lin, Yan Liu, Sumithra Mandrekar, Lawrence H. Schwartz, Lalitha Shankar, Patrick Therasse, Lesley Seymour, RECIST working group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: The mode of action of targeted cancer agents (TCAs) differs from classic chemotherapy, which leads to concerns about the role of RECIST in evaluating tumor response in trials with TCAs. We investigated the performance of RECIST using a pooled database from 50 clinical trials with at least one TCA. METHODS: We examined the impact of the number of target lesions (TLs) on within-patient variability of tumor response. The prognostic effect of TL response (at 12 weeks or on study on the basis of a maximum five TLs) on survival was studied through landmark and time-dependent Cox models adjusted for baseline tumor load, occurrence of new lesions, or unequivocal progression of nontarget disease. RESULTS: Data were obtained from 23,259 patients with cancer (36% lung, 28% colorectal, 11% breast, and 25% other); 15,620 received TCAs, predominantly transduction or angiogenesis inhibitors, as a single agent (37%), combined with other TCAs (7%), or as chemotherapy (56%); 28% received chemotherapy only; and 5% received best supportive care or placebo. A total of 17,222 patients contributed to the analyses. Within-patient variability decreased with increasing number of TLs, similarly for TCAs (with/without chemotherapy) and chemotherapy only. Mixed responses occurred proportionally in all treatment classes. Landmark analyses showed an ordinal relationship between percentage change from baseline to 12 weeks and overall survival, and demonstrated a clear distinction between tumor shrinkage and progressive disease according to RECIST. Time-dependent analysis showed no marked improvement in the ability to predict survival on the basis of TL tumor growth compared with nontarget progression or new lesion occurrence, regardless of treatment. Similar results were seen for major tumor types and different classes of TCAs. CONCLUSION: This work reinforces that RECIST version 1.1 perform well for response assessment of TCAs.
Original languageEnglish
Pages (from-to)1102-1110
JournalJournal of Clinical Oncology
Volume37
Issue number13
DOIs
Publication statusPublished - 1 Jan 2019

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