Abstract 1914P
Background
VEGF and FGFR play major roles in MPM tumorigenesis. Bevacizumab(bev)-platinum-pemetrexed (PP) with bev maintenance improved progression-free (PFS) and overall survival (OS) in the MAPS trial. N is an angiokinase inhibitor with antifibrotic properties targeting VEGF1-3, PDGFRA/B, FGFR1-3, SRC, ABL. VEGF inhibitors previously showed encouraging activity and N’s role as switch maintenance remained unknown. During enrolment, the LUME-Meso phase III trial reported no OS improvement for N-PP and N maintenance in epithelioid MPM and cediranib-PP demonstrated no significant PFS benefit (SWOG S0905).
Methods
We enrolled treatment naïve unresectable MPM (all histology), adequate organ function, no unstable co-morbidities, no N contraindication, performance status 0-2 and no progression after 4-6 cycles PP. Patients(pts) were randomized to N 200mg BID or placebo, continued until loss of clinical benefit, toxicity, or death. Primary endpoint was PFS, secondary endpoints were OS, time to treatment failure (TTF), overall response rate (ORR) and safety. 114 pts were planned for recruitment to target PFS HR=0.62.
Results
The study closed due to poor accrual with 37 pts randomized. We present final analyses. Demographics/efficacy shown (Table). Grade≥3 adverse events (AEs) were observed in 27.8%(N) vs 10.5%(placebo), no deaths from toxicity. Commonest AEs were typical for N. Table: 1914P
N, n=18 | Placebo, n=19 | HR (95% CI) | |
Median follow up (mo) | 48.7 | 42.4 | |
M:F (n) | 12:6 | 15:4 | |
Epithelioid (%) | 78 | 79 | |
Median treatment duration (weeks) | 11.8 | 24.3 | |
PFS (mo) | 3.4 | 4.6 | 2.25 (1.07-4.73) |
OS (mo) | 13.1 | 38.9 | 2.38 (1.05-5.43) |
TTF (mo) | 2.0 | 4.6 | 2.55 (1.22-5.32) |
Further anticancer treatment (%) | 72 | 79 | |
Further immunotherapy (%) | 46 | 87 |
Conclusions
Despite closing early, whilst imbalanced by subsequent immunotherapy use, NEMO suggests a detrimental effect of maintenance N compared with placebo (Sponsor, EORTC; Funding, Boehringer Ingelheim/EORTC; NCT02863055).
Clinical trial identification
EORTC-08112-LCG; NCT02863055.
Editorial acknowledgement
Legal entity responsible for the study
EORTC.
Funding
Boehringer Ingelheim.
Disclosure
S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx, AnHeart, Arcus Biosciences, Ellipses, Gilead, IO Biotech, Mirati; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Novocure, PharmaMar; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, GSK, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Committee, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Advisory Board Member, Unpaid: Lung Cancer Europe. All other authors have declared no conflicts of interest.
Resources from the same session
1475TiP - Fruquintinib in combination with sintilimab and CAPEOX as first-line treatment for advanced G/GEJ cancer: A phase Ib/II clinical trial (FUNCTION)
Presenter: Bei-Bei Chen
Session: Poster session 18
1505P - Exploratory biomarker analysis of the NEONAX trial for response prediction to perioperative (PO) and adjuvant (A) Gem-nabPac chemotherapy (CTX) in resectable PDAC patients (rPDAC Pts)
Presenter: Anton Lahusen
Session: Poster session 18
1506P - ctDNA testing based on deep NGS predicts treatment efficacy and prognosis in advanced pancreatic cancer patients
Presenter: Tingting You
Session: Poster session 18
1507P - Revolutionizing clinical trials: Harnessing artificial intelligence for optimized phase III studies in pancreatic cancer
Presenter: Marie-Edith Bonneterre
Session: Poster session 18
1509P - Cytokines and ductal pancreatic adenocarcinoma: Exploring their relationship with prognosis and molecular subtypes
Presenter: Laura Gutierrez Sainz
Session: Poster session 18
1510P - Exploration of circulating free bacterial DNA as a biomarker for therapy response in metastatic and locally advanced pancreatic cancer patients treated with systemic chemotherapy
Presenter: Sai Surendran
Session: Poster session 18
1511P - The influence of intratumoral bacteria and peri-operative antibiotic treatment on the outcome of resected pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy
Presenter: Steffen Ormanns
Session: Poster session 18
1512P - The role of pancreaticoduodenectomy for octogenarians with pancreatic cancer
Presenter: Keita Sonoda
Session: Poster session 18
1513P - Impact of symptom and functional burden on survival in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Omali Pitiyarachchi
Session: Poster session 18