Early Tumor Shrinkage and Depth of Response as Predictors of Favorable Treatment Outcomes in Patients with Metastatic Colorectal Cancer Treated with FOLFOX Plus Cetuximab (JACCRO CC-05)

Abstract

Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy (UMIN000004197).

Early tumor shrinkage and depth of response in patients with advanced gastric cancer: a retrospective analysis of a randomized phase III study of first-line S-1 plus oxaliplatin vs. S-1 plus cisplatin

“…In the recent years, several retrospective studies [1][2][3][4][5] and one prospective study [6] have shown that early tumor shrinkage (ETS), defined as a % decrease in the sum of the longest diameters of the target lesions at the first evaluation (usually week 6 or 8), is a good predictor of the long-term outcomes of the first-line treatment for metastatic colorectal cancer (mCRC). In most of these reports, ETS of 20% was used to classify as responders or non-responders [2][3][4][5][6]. ETS is considered as an on-treatment marker that reflects tumor sensitivity to anticancer therapy [2,7,8] and thus could be a useful clinical decision-making tool.…”

“…ETS is considered as an on-treatment marker that reflects tumor sensitivity to anticancer therapy [2,7,8] and thus could be a useful clinical decision-making tool. In addition, depth of response (DpR) defined as the maximum tumor shrinkage of individual patient during the treatment has been reported to be associated with survival in mCRC patients [5,6].…”

The importance of the initial response to cancer treatment in predicting longer overall survival

“…In a prospective study of 54 Japanese patients with mCRC (KRAS wildtype) treated with FOLFIRI plus cetuximab, Tsuji et al demonstrated that DepOR was associated with OS and postprogression survival (PPS) on a study level. They also determined that the association between DepOR and OS and PPS in patients with the largest lesions (≥5.05 mm) was driving this response [16]. In another example, Cremolini et al demonstrated that DepOR and ETS were significantly associated with survival in mCRC patients treated with FOLFOXIRI + bevacizumab or FOLFIRI + bevacizumab and that the patients treated with FOLFOXIRI + bevacizumab had a larger DepOR and better survival, and DepOR was equivalent to RECIST in predicting survival [17].…”

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

“…14 An association between both ETS and DpR and survival outcomes has also been observed in retrospective and prospective trials of cetuximab. 13,[17][18][19] In the CRYSTAL and OPUS trials, which evaluated cetuximab with and without FOLFIRI and FOLFOX4, respectively, ETS was significantly associated with progression-free survival in both the cetuximab plus chemotherapy and chemotherapy-alone treatment arms. 13 In retrospective analysis of the TRIBE trial, treatment with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab versus FOLFIRI plus bevacizumab improved ETS and DpR, and both response parameters predicted survival.…”

“…13 In retrospective analysis of the TRIBE trial, treatment with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab versus FOLFIRI plus bevacizumab improved ETS and DpR, and both response parameters predicted survival. 13,15,[17][18][19] Tumor location has also been highlighted as an important factor to consider in treatment decisions for mCRC. Left-sided tumors are more common and are associated with a better prognosis and increased response to anti-EGFR treatment.…”