Abstract 349P
Background
Angiogenesis factors have been reported as prognostic and predictive biomarkers of AIs for mCRC, but its significance as a predictor of efficacy in 2L chemo combined with AIs has not been established.
Methods
In 295 enrolled patients (pts) with mCRC receiving chemo plus AI in 2L treatment from Sep 2017 to Dec 2020, serial plasma samples were prospectively collected at the time points of pre- and post-treatment. 17 plasma angiogenesis factors were analyzed by the multiplex assay with Luminex technology. Interactions of their pre-treatment measurements with treatment groups on PFS were assessed via Cox proportional hazards model. The strength of interactions was examined using estimated generalized propensity score as weight, and the continuous plasma angiogenesis variables were dichotomized according to the median. The significance level for the interaction was defined as two-sided p ≤0.1.
Results
283 pts were included in adjusted 2L cohort (chemo plus bevacizumab [BEV [reference]: n=100], FOLFIRI plus ramucirumab [RAM: n=98], FOLFIRI plus aflibercept [AFL: n=85]). Baseline characteristics in this cohort were as follows; median age 67 years; male 57.2%; left-sided tumor 70.3%; RAS mutant 50.2%; prior BEV 72.8%. Propensity-score weighted Cox model for PFS compared RAM with BEV showed significant interactions in HGF (median 174 pg/mL, High: HR 1.278, Low: HR 0.737, interaction p = 0.0485), sVEGFR-1 (median 985 pg/mL, High: HR 0.692, Low: HR 1.419, interaction p = 0.0106), and sVEGFR-3 (median 17200 pg/mL, High: HR 0.658, Low: HR 1.396, interaction p = 0.0065). On the other hand, there were no significant interactions for PFS compared AFL with BEV. Table: 349P
| Below median | Above median | Interaction p-value∗ | |||
| BEV | RAM | BEV | RAM | Below vs above median | |
| HGF | 6.9 m | 6.7 m | 4.0 m | 2.1 m | 0.0485 |
| sVEGFR-1 | 6.2 m | 3.9 m | 5.9 m | 5.8 m | 0.0106 |
| sVEGFR-3 | 6.4 m | 3.7 m | 5.7 m | 6.7 m | 0.0065 |
| Median PFS, ∗defined as p ≤0.1 |
Conclusions
Pre-treatment plasma HGF, sVEGFR-1 and sVEGFR-3 could be biomarkers that contribute to the optimal regimen selection of FOLFIRI plus RAM or chemo+BEV in 2L treatment of mCRC.
Clinical trial identification
UMIN000028616. 2017/09/21.
Editorial acknowledgement
Legal entity responsible for the study
Clinical Research and Medical Innovation Center, Hokkaido University Hospital.
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., Yakult Honsha Co., Ltd., Merck Biopharma Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd.. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol-Byers Squibb, Chugai Pharmaceutical, Takeda, Taiho Pharmaceutical, Merck Biopharma, Daiichi-Sankyo, Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda, Eli Lilly Japan. H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma; Financial Interests, Institutional, Invited Speaker: Takeda, Ono, Daiichi Sankyo. T. Masuishi: Financial Interests, Personal, Invited Speaker: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol myers squibb; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer-Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly. M. Shiozawa: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eli Lilly K.K., Merck Biopharma Co., Ltd., Yakult Honsha Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.. H. Bando: Financial Interests, Institutional, Research Grant: Ono pharmaceutical; Other, Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. T. Nishina: Financial Interests, Personal, Invited Speaker: Taiho pharmaceutical, Ono pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi sankyo, Ono pharmaceutical, Bristol Myers Squibb, Astellas. H. Yasui: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb, Daiichi-Sankyo, Terumo, Eli Lilly Japan, Merck Biopharma, Yakult Honsha, Bayer Yakuhin; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi-Sankyo, Ono Pharmaceutical, Astellas Pharma. T. Ohta: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan, Chugai Pharma, Teijin Pharma, Takeda Pharmaceutical Company Limited., Taiho Pharmaceutical Co., Ltd., Eisai Co., Ltd., Yakult Honsha; Financial Interests, Personal and Institutional, Invited Speaker: Takeda Pharmaceutical Company Limited.. N. Takahashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd.. T. Denda: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., LTD, Daiichi Sankyo Company, Limited; Financial Interests, Institutional, Funding: Ono Pharmaceutical. T. Kato: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical CO., LTD, Eli Lilly and Company, ONO Pharmaceutical Co, Takeda Pharmaceutical Company Limited, Asahikasei; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co. E. Oki: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bayer, Eli Lilly, Bristol-myers squibb. S. Nomura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, KyowaHakko Bio; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Bayer, Ono, MSD; Financial Interests, Institutional, Invited Speaker: Ono, Sanofi, Daiichi Sankyo, Chugai, Pfizer; Financial Interests, Institutional, Research Grant: Taiho, MSD, Ono, Amgen, Genomedia, Sysmex, Daiichi Sankyo, Chugai, Boehringer Ingelheim. All other authors have declared no conflicts of interest.