Abstract 463P
Background
Plasma angiogenesis factors are known to be a prognostic factor for mCRC, but its significance as a predictor of efficacy in 2nd-line (2L) chemotherapy (chemo) combined with angiogenesis inhibitors has not been established.
Methods
In this prospective longitudinal study, serial plasma sample collections were done at the time points of pre- and post-treatments in mCRC patients (pts) receiving biologics in either 1st-line or 2L chemo. In this analysis, we investigated the effects of VEGF-A, VEGF-D, and PlGF analyzed by the multiplex assay with Luminex® technology on progression-free survival (PFS) in pts for 2L cohort. The cut-off value in this analysis was defined as the median value of each factor. Statistical analyses were conducted by using log-rank test compared with high and low of each factor.
Results
From Sep 2017 to Dec 2020, 498 patients were enrolled in this study. Among them, 284 pts were included in 2L cohort (Chemo plus bevacizumab [BEV group, n=100], FOLFIRI plus ramucirumab [RAM group, n=99], FOLFIRI plus aflibercept [AFL group, n=85]). Baseline characteristics were similar among groups. Median baseline value of VEGF-A, VEGF-D, and PlGF in 2L cohort were 30.0, 342.5, 18.4 pg/ml, respectively. In the BEV group, patients with low PlGF had significantly longer PFS (7.5 vs 4.2 m, HR 2.35, p<0.01), and patients with high VEGF-A or low VEGF-D tended to have a better PFS, although the difference was not significant. On the other hand, in the RAM and AFL groups, there was no trend toward a difference in PFS between patients with high and low levels of each angiogenesis factor. Table: 463P
| BEV group | RAM group | AFL group | |||||
| Low | High | Low | High | Low | High | ||
| VEGF-A | Median PFS | 5.1 m | 6.4 m | 4.5 m | 4.0 m | 3.8 m | 4.6 m |
| HR, p-value | 0.70, 0.09 | 1.34, 0.20 | 1.05, 0.86 | ||||
| VEGF-D | Median PFS | 6.2 m | 5.6 m | 4.4 m | 4.0 m | 4.5 m | 4.1 m |
| HR, p-value | 1.51, 0.06 | 1.19, 0.45 | 1.09, 0.75 | ||||
| PlGF | Median PFS | 7.5 m | 4.2 m | 5.1 m | 4.0 m | 4.1 m | 4.5 m |
| HR, p-value | 2.35, <0.01 | 1.25, 0.34 | 1.04, 0.88 |
Conclusions
The measurement of VEGF-A, VEGF-D and PlGF may contribute to predicting the efficacy of the 2L chemotherapy plus bevacizumab for mCRC. A final report will be scheduled after the overall survival has matured.
Clinical trial identification
UMIN000028616. 2017/09/21
Editorial acknowledgement
Legal entity responsible for the study
SCRUM-Japan GI-SCREEN.
Funding
Japan Agency for Medical Research and Development.
Disclosure
S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Eli Lilly K.K.; Takeda Pharmaceutical Co., Ltd.; Bayer Yakuhin, Ltd; Bristol-Myers Squibb Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; MSD K.K.; Ono Pharmaceutical Co., Ltd.; Medical & Biological Laboratories Co., Ltd.; Yakult Honsha Co., Ltd.; Merck Biopharma Co., Ltd.; Sanofi K.K.. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Yakult Honsha Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Bayer Yakuhin, Ltd.; Merck Biopharma Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; Eli Lilly K.K.; Sanofi K.K.; Ono Pharmaceutical Co., Ltd.; MSD K.K.; Bristol-Myers Squibb Co., Ltd.; Financial Interests, Institutional, Funding: Taiho Pharmaceutical Co., Ltd.. H. Yasui: Financial Interests, Institutional, Funding: MSD K.K.; Ono Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Astellas Pharma Inc.; BeiGene; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Bristol-Myers Squibb Co., Ltd.; Terumo Corporation; Eli Lilly K.K.; Merck Biopharma Co., Ltd.; Yakult Honsha Co., Ltd.; Bayer Yakuhin, Ltd.; Takeda Pharmaceutical Co., Ltd.. Y. Sunakawa: Financial Interests, Institutional, Funding: Takeda Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; Sanofi K.K.; Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Co., Ltd.; Eli Lilly K.K.; Chugai Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; Bristol-Myers Squibb Co., Ltd.; Sanofi K.K.. H. Satake: Financial Interests, Institutional, Funding: Ono Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd.; Bristol-Myers Squibb Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Eli Lilly K.K.; Merck Biopharma Co., Ltd.; MSD K.K.; Ono Pharmaceutical Co., Ltd.; Sanofi K.K.; Taiho Pharmaceutical Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.. T. Yoshino: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly K.K.; Merck Biopharma Co., Ltd.; Bayer Yakuhin, Ltd.; Ono Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Funding: Taiho Pharmaceutical Co., Ltd.; Sumitomo Dainippon Pharma Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Amgen Inc.; Ono Pharmaceutical Co., Ltd.; Parexel International Corporation; MSD K.K.; Daiichi Sankyo Co., Ltd.; Sanofi K.K.. All other authors have declared no conflicts of interest.