Predictability of survival outcome by early tumor shrinkage (ETS) at 8 weeks with cutoff value of 20% in metastatic colorectal cancer (mCRC) patients treated with mFOLFOX6 plus bevacizumab (bev) or FOLFIRI plus bev as first-line chemotherapy (1st-CTx): Validation in the phase III WJOG4407G trial.

Abstract

729 Background: We reported that ETS at 8 weeks with cutoff value of 20% is the best candidate for predicting overall survival (OS) in mCRC patients who received 1st-CTx in the retrospective study (Kito, ESMO, 2015), where ETS was estimated by the tumor growth inhibition model (Claret, JCO, 2013). The objective of the study was to validate our proposed evaluation time and cutoff value for ETS in the phase III WJOG4407G trial which showed equivalent efficacy of mFOLFOX6+bev and FOLFIRI+bev as 1st-CTx for mCRC (Yamazaki, Ann Oncol, 2016). Methods: Tumor shrinkage ratio (TSR), which is the relative change in the sum of the longest diameters of target lesions according to the RECIST between before and during 1st-CTx, was calculated using actually measured tumor size data. Cutoff values of TSR for ETS and allowance ranges for measurement time of tumor size were evaluated. The association between ETS and OS was investigated by Cox regression model. In multivariate analyses, the general prognostic factors of mCRC, such as ECOG performance status (PS), prior history of adjuvant chemotherapy (AC), baseline tumor size (bTS), serum alkaline phosphatase (ALP) and white blood cell (WBC), were adjusted. Results: Of 402 enrolled patients, 305 patients had tumor size data measured within 8 +- 2 weeks. Patient characteristics were: mFOLFOX6+bev/FOLFIRI+bev 153/152; PS 0/1 244/61; AC Yes/No 49/256; median bTS 79 mm (range 10-512); median ALP 274 IU/L (110-1,200); median WBC 6400/mm3(3,030–12,000). In multivariate analyses, ETS at 8 weeks with cutoff value of 20% was most significantly associated with OS showing hazard ratio (HR) of 0.53 (95%CI: 0.38-0.74, p < 0.001). Moreover, HR of ETS was 0.47 (95%CI: 0.33-0.67, p < 0.001) in using the data during 8 +- 1 weeks (n = 257), while HR was 1.03 (95%CI: 0.41-2.62, p = 0.95) in using the data earlier or later than 8 +- 1 weeks (6 to 7 or 9 to 10 weeks) (n = 48). Conclusions: This analysis supported that ETS with cutoff value of 20% using data within 8 +- 1 weeks is optimal for predicting OS in mCRC patients who received 1st-CTx. Clinical trial information: UMIN000001396.