1097O - The AXINET trial (GETNE1107): Axitinib plus octreotide LAR improves PFS by blinded central radiological assessment vs placebo plus octreotide LAR in G1-2 extrapancreatic NETs

Background

Angiogenesis plays an important role in NET development and progression. Axitinib is a potent and selective VEGFR-1,2,3 inhibitor with proven activity against other vascular-dependent solid tumors. The aim of this double-blind phase II/III randomized study was to assess the efficacy of axitinib in patients (pts) with advanced G1-2 extra-pancreatic NETs.

Methods

Pts were randomized 1:1 to receive octreotide LAR (30 mg IM q4w) with axitinib (5 mg BID) or placebo BID until disease progression or unacceptable toxicity. Randomization was stratified by time from diagnosis to study entry (> or ≤ 12m), primary tumor site (GI tract vs non-GI) and Ki-67 index (≤ 5% vs > 5%). Prior therapy with SSA, IFN and up to 2 lines of systemic treatment was allowed, but not prior VEGF- or VEGFR-targeted drugs. Clinical and/or radiological disease progression within 12 months prior to study entry was required. The primary endpoint was progression-free survival (PFS). PFS results per investigator assessment were presented at ASCO GI 2021. Blinded independent central assessment of PFS is now presented.

Results

256 pts were enrolled, 126 randomized to axitinib and 130 to placebo (G1-2: 29%-71%). Most common primary tumor sites were SI (47%), lung (28%), rectum (6%), UK (8%), gastric (3%) and colon (2%). Prior therapies included SSA (48%), everolimus (13%), chemotherapy (13%), LR tx (7%) and PRRT (3%). ORR per independent radiological assessment was significantly greater in axitinib- vs placebo-treated patients (13.2% vs 3.2%, p=0.0045). PFS per blinded independent central review also significantly favored axitinib-treated patients (median PFS of 16.6 vs 9.9 months in the axitinib vs placebo arms, respectively, HR 0.687, p=0.01). Toxicity was manageable, as previously reported (ASCO GI 2021).

Conclusions

Axitinib demonstrated a significant improvement in PFS in combination with octreotide LAR in pts with advanced progressive G1-2 extra-pancreatic NETs as per independent radiological assessment blinded to treatment allocation, with a tolerable safety profile.

Clinical trial identification

NCT01744249.

Editorial acknowledgement

Daniela Morales-Espinosa MD, MSc.

Legal entity responsible for the study

GETNE (Grupo Español de Tumores Neuroendocrinos).

Funding

Pfizer.

Disclosure

R. Garcia-Carbonero: Financial Interests, Personal, Speaker’s Bureau, Scientific advice: AAA; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Advanz Pharma; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Bayer; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: BMS; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: HMP; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Ipsen; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Merck; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Midatech Pharma; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: MSD; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Novartis; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: PharmaMar; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Pfizer; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Roche; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Sanofi; Financial Interests, Personal, Speaker’s Bureau, Scientific advice: Servier; Financial Interests, Personal, Funding, Financial support to IIT evaluating Axitinib in NETs: Pfizer; Financial Interests, Personal, Funding, Financial support to IIT evaluating Nivolumab in NECs: BMS; Financial Interests, Personal, Funding, Financial support to IIT evaluating Pembrolizumab-Olaparib in CRC: MSD; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: ARMO Biosciences; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Astra Zeneca; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Pfizer; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Novartis; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Ipsen; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Roche; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Pharmacyclics; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Boston Biomedicals; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Merck; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: MSD; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Amgen; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Sanofi; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Bayer; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Bristol-Myers-Squibb; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Boerhinger Ingelheim; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Sysmex; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Gilead Sciences; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Servier; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Adacap; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: VCN; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: Lilly; Financial Interests, Institutional, Funding, Financial support for the conduct of clinical trials or for molecular diagnostic platforms: PharmaMar; Non-Financial Interests, Personal, Leadership Role, Member of the executive committee: GETNE (Spanish Neuroendocrine Tumor Cooperative Group; Non-Financial Interests, Personal, Leadership Role, Member of the executive committee: ENETS; Non-Financial Interests, Personal, Principal Investigator, Global PI of clinical trial of Axitinib in NETs: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Global PI of clinical trial of nivolumab and chemotherapy in NETs: BMS; Non-Financial Interests, Personal, Principal Investigator, Global PI of clinical trial of pembrolizumab-olaparib in CRC: MSD; Non-Financial Interests, Personal, Member: EORTC; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: SEOM; Non-Financial Interests, Personal, Member: TTD; Non-Financial Interests, Personal, Member: GEMCAD. M. Benavent: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role: PFIZER; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: ROCHE; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: Ipsen. D. Castellano: Financial Interests, Personal, Invited Speaker: full DOI at ESMO profile. T. Alonso-Gordoa: Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Ipsen; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Janssen-Cilag; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: BMS; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Eisai; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Astra Zeneca; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Ipsen; Financial Interests, Institutional, Principal Investigator: GSK-Novartis; Financial Interests, Institutional, Principal Investigator: Clovis; Financial Interests, Institutional, Principal Investigator: Nektar Therapeutics; Financial Interests, Institutional, Principal Investigator: Janssen-Cilag; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Bayer; Non-Financial Interests, Institutional, Project Lead: Pfizer; Non-Financial Interests, Institutional, Project Lead: Roche; Non-Financial Interests, Institutional, Project Lead: Ipsen. A. Teulé: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Astra Zeneca; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Astra Zeneca; Financial Interests, Personal, Advisory Role: AAA; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Other, Travel grants: Novartis; Financial Interests, Personal, Other, Travel grants: Ipsen; Financial Interests, Personal, Other, Travel grants: Astra Zeneca; Financial Interests, Personal, Other, Travel grants: AAA; Financial Interests, Personal, Other, Travel grants: Pfizer. A. Custodio: Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: IPSEN; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Pfizer; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Novartis; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: MSD; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: BMS; Financial Interests, Personal, Invited Speaker, Consultancy or advisory role: Lilly; Financial Interests, Institutional, Principal Investigator: Ipsen; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: EISAI; Financial Interests, Institutional, Principal Investigator: Astra Zeneca; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: BeiGene; Non-Financial Interests, Personal, Leadership Role, Member of the GETNE tumor board: GETNE. S. Tafuto: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Principal Investigator: Ipsen; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: PFIZER; Financial Interests, Personal, Principal Investigator: Novartis. F. Spada: Financial Interests, Personal, Advisory Board, Travel grant: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Institutional, Principal Investigator: GETNE; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: MSD; Non-Financial Interests, Personal, Leadership Role, Coordinator of Neuroendocrine Neoplasms guidelines: Italian Association of Medical Oncology (AIOM); Non-Financial Interests, Personal, Leadership Role, Executive board meamber: Italian Association of Neuroendocrine Tumors (ITANET). C. López: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AAA; Non-Financial Interests, Personal, Principal Investigator: Ipsen; Non-Financial Interests, Personal, Principal Investigator: ROCHE; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: Novartis. T. Ibrahim: Financial Interests, Personal, Other, Consultancy: EISAI; Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel grant: Ipsen; Financial Interests, Personal, Other, Travel grant: Pharmamar; Financial Interests, Personal, Other, Travel grant: Novartis. M.J. Villanueva Silva: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Glaxo-Smithkline; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Pfizer; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Roche; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Novartis; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Sanofi; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Celgene; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: AstraZeneca; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: BMS; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Merck Serono; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Merck Sharp and Dohme; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Janssen-Cilag; Financial Interests, Institutional, Funding, Institutional research funding for conducting phase II and III clinical trials: Bayer. V. Iranzo: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications; Financial Interests, Personal, Invited Speaker: Astra Zeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche. P. García-Alfonso: Financial Interests, Personal, Invited Speaker: Ipsen. E. González-Flores: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: AAA; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis. E. Grande: Financial Interests, Personal, Invited Speaker: Adecap; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Astra Zeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Caris Life Sciences; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Eusa Pharma; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck KGa; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: ONCODNA (Biosequence); Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Non-Financial Interests, Institutional, Research Grant: Astellas; Non-Financial Interests, Institutional, Research Grant: Astra Zeneca; Non-Financial Interests, Institutional, Principal Investigator: Ipsen; Non-Financial Interests, Institutional, Research Grant: Lexicon; Non-Financial Interests, Institutional, Research Grant: MTEM/Threshold; Non-Financial Interests, Institutional, Research Grant: Nanostring Technologies; Non-Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Roche. G. Crespo: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: IPSEN; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: EISAI; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: EUSA Pharma; Financial Interests, Personal, Invited Speaker: Pierre Fabre. A. Carmona-Bayonas: Financial Interests, Personal, Project Lead: Lilly; Financial Interests, Personal, Project Lead: BMS. J. Capdevila: Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Amgen; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Bayer; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: AAA; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: Eisai; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: Ipsen; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: ITM; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Hudchinson Pharma; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Lilly; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Merck; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: NOVARTIS; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker - Research grant: Pfizer; Financial Interests, Personal, Speaker’s Bureau, Advisory Board - Invited speaker: Sanofi. All other authors have declared no conflicts of interest.