Abstract 104P
Background
Previous studies showed that angiogenesis-related factors could play a key role in the development of immunosuppressive microenvironment and may serve as predictors for chemotherapy. This biomarker study was focused on the dynamics of angiogenesis-related factors in clinical trial of combination therapy with PTX, RAM plus Nivo for AGC as 2nd-line treatment, with expected antitumor activity [Kadowaki S, et al, Ann Oncol, 2019 Jul;30 Suppl4].
Methods
We evaluated plasma concentrations of angiogenesis-related factors in plasma at baseline, 4 weeks after treatment, and progression and the association with clinical outcomes in patients with available samples. PlGF, VEGF-A/D, HGF, IL-6/8, angiopoietin-2, sNeurophilin-1, sICAM-1, sVCAM-1, sVEGFR-1/2/3, and INF-γ were measured by magnetic bead panel Milliplex xMAP kits, Flt3L and sPD-L1 by ELISA. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Fisher’s exact test was used to compare IL-6 level and response.
Results
Forty-one of 43 AGC pts were enrolled: median age, 66 years; male, 82.9%; ECOG PS 1, 48.8%; and diffuse type, 43.9%. Plasma average levels of PlGF, VEGF-A/D, and sVCAM-1 significantly increased after treatment; whereas angiopoietin-2 exhibited a decrease during treatment. When the median value was adopted as cut-off value, high levels of IL-8 and sICAM-1 at baseline were significantly associated with shorter OS [HR 2.69 (95%CI 1.28-5.92), p = 0.009; HR 3.50 (95%CI 1.63-8.16), p = 0.001, respectively]; whereas, comparable PFS. The elevation of IL-6 level at 4 weeks were detected in 8 (35%) of 23 responders and in only 2 (15%) of 13 non-responders (P = 0.21). Moreover, it was significantly associated with favorable OS [HR 0.20 (95%CI 0.05-0.60), p = 0.002], but not PFS.
Conclusions
This study identified baseline plasma levels of IL-8 and sVCAM-1 as potential prognostic markers corresponding to favorable OS for combination therapy of PTX, RAM plus Nivo in patients with AGC. In addition, the increase in IL-6 level at 4 weeks may predict clinical benefit from the combination therapy.
Clinical trial identification
UMIN000025947.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ono pharmaceutical company.
Disclosure
N. Izawa: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd ; Research grant/Funding (institution): Eli Lilly Japan. S. Ohta: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd . S. Kadowaki: Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan. K. Minashi: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd. Y. Sunakawa: Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan. K. Muro: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd ; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly Japan; Advisory/Consultancy: Nihon Kayaku. T. Nishina: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): ONO Pharmaceutical CO.,Ltd; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly Japan; Honoraria (self): Nihon kayaku. S. Hironaka: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd. T.E. Nakajima: Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Ono Pharmaceutical Co., LTD ; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Nihon kayaku. Y. Kawakami: Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.