132P - The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

Background

Anti-vascular endothelial growth factor (VEGF) agents like bevacizumab have improved of outcome in patients with various cancers in the era of immunotherapy, but predictive biomarkers that select patients who will benefit from the addition of such anti-VEGF agents to immune checkpoint blockade have not been elucidated.

Methods

We conducted a preplanned, prospective biomarker study affiliated with the APPLE study (Trial number: UMIN000037326), which was an open-label, randomized phase 3 trial evaluating the efficacy of the bevacizumab in combination with a Programmed-cell death (PD)-1 pathway inhibitor, atezolizumab, plus platinum chemotherapy in metastatic, nonsquamous non-small cell lung cancer (NSCLC) patients. A total of 152 patients were enrolled in this biomarker study. By using newly developed Enzyme-linked immunosorbent assay system, we investigated levels of VEGF-A (total VEGF-A) and its two variant isoforms VEGF₁₆₅ and VEGF₁₂₁ in the peripheral blood serum at baseline before the initiation of treatment. Each VEGF values were defined as high if higher than the median and low if lower than the median in all analyzed populations, and the correlations of those levels with treatment response were analyzed.

Results

We revealed that in epidermal growth factor receptor wild-type (EGFR-WT) patients with the low level of VEGFs, especially total VEGF-A, the addition of bevacizumab to atezolizumab and chemotherapy significantly improved the progression-free survival in comparison to those in patients treated with chemotherapy plus atezolizumab (hazard ratio (HR), 0.46; 95% CI, 0.26 to 0.82) compared with those with high VEGF (HR, 1.40; 95% CI, 0.78 to 2.51).

Conclusions

Our result demonstrates for the first time that measuring VEGF-A and its isoforms in the serum may identify nonsquamous NSCLC patients with EGFR-WT who will obtain improved prognosis by the addition of bevacizumab to the PD-1 pathway inhibitor’s treatment, and further research into a role for VEGF-A in tumor immunity is warranted.

Clinical trial identification

UMIN000037326.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Has not received any funding.

Disclosure

K. Tanaka: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, Takeda Pharmaceutical, Pfizer, MSD, Novartis, Bristol Myers Squibb. Y. Shiraishi: Financial Interests, Personal, Funding: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol Myers Squibb, Taiho Pharmaceutical, Kyowa Kirin. H. Daga: Financial Interests, Personal, Invited Speaker: Chugai pharmaceutical, AstraZeneca. K. Azuma: Financial Interests, Personal, Invited Speaker, Lecture fee: AstraZeneca, MSD, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Takeda Pharmaceutical. K. Nishino: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical CO., LTD., MSD, Amgen, Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Daiichi Sankyo Company, LIMITED, Nippon Kayaku Co.,Ltd., Daiichi Sankyo Co., Ltd., Mochida Pharmaceutical Co., Ltd., Yuyu Teijin Medicare Inc., Varian Medical Systems, Inc.; Financial Interests, Personal, Advisory Board: Pfizer, Janssen Pharmaceutical K.K., AstraZeneca; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceutical CO., LTD., Taiho Pharmaceutical CO., LTD., MSD, AbbVie, Daiichi Sankyo Company, Limited, Amgen, Eli Lilly, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai pharmaceutical, Merus, AstraZeneca. M. Mori: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kyowa hakko Kirin, MSD, Nihon Kayaku, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, AbbVie. H. Saito: Financial Interests, Institutional, Funding: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer. A. Hata: Financial Interests, Institutional, Funding: MSD, Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca. T. Sakaguchi: Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, Chugai Pharmaceutical, Merck, Ono Pharmaceutical, AstraZeneca. T. Kozuki: Financial Interests, Institutional, Funding: Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Kyowa hakko Kirin, Merck, Daiichi Sankyo, Amgen, AbbVie, Sanofi, Labcorp development Japan, IQVIA Services Japan, Gilead Sciences, Pfizer, Bayer; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Pfizer, Daiichi Sankyo, Bayer, AbbVie, Boehringer Ingelheim, Merck, Nihon Kayaku, Novartis, Daiichi Sankyo, Takeda Pharmaceutical, Bayer, Sawai, Amgen, Eisai; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, MSD, Pfizer, Kyowa hakko Kirin. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis, Pfizer Inc., Amgen Inc., Merck biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis; Financial Interests, Institutional, Research Grant: MSD K.K; Financial Interests, Institutional, Local PI: AstraZeneca, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Amgen Inc., Janssen Pharmaceutical K.K., Novartis, Eisai, Eli Lilly Japan; Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Sanofi. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Incyte biosciences Japan, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb Company, Medical Mobile Communications co., Ltd, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Otuka Pharmaceutical Factory, Inc., M3, Inc., Hisamitsu Pharmaceutical Co., Inc., Global Health Consulting Japan Co., Ltd., The Yomiuri Shimbun; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Personal, Writing Engagement: Yodosha Co., Ltd.; Financial Interests, Institutional, Research Grant: Amgen Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Ep-Crsu Co., Ltd., EPS Corporation., Eisai Co., Ltd., GSK K.K., IQVIA Services Japan K.K., Janssen Pharmaceutical K.K., Kobayashi Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd., Pra Healthsciences, srl Medisearch Inc., Syneos Health Clinical K.K., Sanofi K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Pfizer Japan Inc., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin, Ltd, AstraZeneca K. K., AbbVie Inc., A2 Healthcare Corp., Japan Clinical Cancer Research Organization, Thoracic Oncology Research Group. I. Okamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Takeda Pharmaceutical, Daiichi Sankyo, MSD, Pfizer, Taiho Pharmaceutical, Novartis; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, MSD, Taiho Pharmaceutical, Novartis. All other authors have declared no conflicts of interest.