American Association for Cancer Research
15357163mct160196-sup-164545_2_supp_3562296_595r3z.docx (54.36 kB)

Supplementary Table S2 from TP53 Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics

Download (54.36 kB)
journal contribution
posted on 2023-04-03, 14:40 authored by Jennifer J. Wheler, Filip Janku, Aung Naing, Yali Li, Bettzy Stephen, Ralph Zinner, Vivek Subbiah, Siqing Fu, Daniel Karp, Gerald S. Falchook, Apostolia M. Tsimberidou, Sarina Piha-Paul, Roosevelt Anderson, Danxia Ke, Vincent Miller, Roman Yelensky, J. Jack Lee, David Hong, Razelle Kurzrock

Multivariate analysis of factors affecting treatment outcomes in 106 patients with TP53 molecular alterations versus 82 patient with TP53 wild-type, by individual factors of MDACC score vs MDACC score (only factors with p value< 0.02 in univariate were included in multivariate analysis)*


Foundation Medicine, Inc.



TP53 tumor-suppressor gene mutations are among the most frequent abnormalities in cancer, affecting approximately 40% of patients. Yet, there is no accepted way to target these alterations in the clinic. At the same time, antagonists of VEGFR or its ligand are best-selling oncology drugs, with multiple, expensive compounds approved. Although only a subset of patients benefit from these antiangiogenesis agents, no relevant biomarker has been identified. Interestingly, TP53 mutations upregulate VEGF-A and VEGFR2. We prospectively enrolled 500 patients, to be interrogated by comprehensive genomic profiling (CGP) (next-generation sequencing, 236 genes), and to be matched, whenever possible, with targeted agents. Herein, we analyze outcomes based on VEGF/VEGFR inhibitor treatment and presence of TP53 mutations. Of the 500 patients, 188 (37.6%; with ≥1 alteration) were treated; 106 (56% of 188) had tumors that harbored TP53 mutations. VEGF/VEGFR inhibitor therapy was independently associated with improvement in all outcome parameters [rate of stable disease (SD) ≥6 months/partial and complete remission (PR/CR); (31% versus 7%; TP53-mutant patients (who received no other molecular-matched agents) treated with versus without VEGF/VEGFR inhibitors), time-to-treatment failure, and overall survival (multivariate analysis: all P ≤ 0.01)] for the patients harboring TP53-mutant cancers, but improvement was not seen in any of these parameters for patients with TP53 wild-type neoplasms. We conclude that TP53 mutations predict sensitivity to VEGF/VEGFR inhibitors in the clinic. TP53 alterations may therefore be a ready biomarker for treatment with antiangiogenesis agents, a finding of seminal importance across the cancer field. Mol Cancer Ther; 15(10); 2475–85. ©2016 AACR.