Abstract 1174P
Background
Most appropriate sequence of all available systemic therapies in advanced pNETs is not well stablished and very often patients (pts) need additional treatments after progression to standard ones. Resistance to antiangiogenic therapies may be a transient mechanism that may allow rechallenge of prior drugs after a washout and under pressure of mechanistically different therapies. The RESUNET trial aimed to evaluate the efficacy and safety of the rechallenge with sunitinib in pts with sunitinib-refractory pNETs.
Methods
Phase II, single-arm, multicentre study in pts with ECOG ≤2 and confirmed G1-2 (Ki67 <20%) metastatic pNETs. Pts received sunitinib at 37.5 mg/day after prior progression to sunitinib and at least one other interspersed systemic therapy with a different mechanism of action (non-antiangiogenic drugs). Primary endpoint was progression-free survival (mPFS).
Results
Eleven pts, median age 55y, were included from Feb-2017 to May-2019. Median Ki67 index was 15%. Most pts had liver involvement (91%), and 63.6% had at least two metastatic sites. Prior systemic treatments before first sunitinib included SSA (100%), chemotherapy (63.6%) and other (27.3%). Mean number of systemic therapies between sunitinib treatments was 1.6 (range: 1-3), being everolimus the most frequent (91%). Median time on sunitinib rechallenge treatment was 23 weeks (range: 8-69). Overall response rate and clinical benefit rate (ORR + SD) were 9.1% and 72.7% (95%CI: 0.0-26.1 and 46.4-99.0), respectively. With a median follow-up of 10 months, mPFS was 7.2 months (95%CI: 4.0-10.5). Most frequent toxicities were asthenia (55%) and neutropenia (27%). Grade 3 toxicities were neutropenia (18%) and hand-foot syndrome, hypercalcemia, diarrhea and stomatitis (9%).
Conclusions
Rechallenge with sunitinib seems active and safe in pts with sunitinib-refractory and progressing pNETs population. This is the first study to evaluate prospectively the hypothesis that resistance to sunitinib may be transient in pNETs. The study needed to stop earlier due to low recruitment rate.
Clinical trial identification
NCT02713763; EudraCT 2015-005774-37.
Editorial acknowledgement
Legal entity responsible for the study
Grupo Español de Tumores Neuroendocrinos (GETNE).
Funding
Pfizer.
Disclosure
E. Grande: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eusa Pharma; Advisory/Consultancy: MSD; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Adacap; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution): Lexicon; Advisory/Consultancy: Celgene; Advisory/Consultancy: Janssen; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MTEM/Threshold. T. Alonso: Advisory/Consultancy: IPSEN; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Janssen-Cilag. J. Capdevila Castillón: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Advanced Accelerator Applications; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: ITM; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sirlex; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Research grant/Funding (institution): AstraZeneca. J. Hernando: Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Angelini. R. Garcia-Carbonero: Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Advanz Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: HMP; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Midatech Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): PharmaMar; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Servier; Research grant/Funding (self): ARMO Biosciences; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Boston Biomedicals; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Sysmex; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Adacap; Research grant/Funding (institution): VCN; Research grant/Funding (institution): Lilly; Leadership role, Senior leadership roles: GETNE, ENETS, SAG-O, EMA; Leadership role, Non-remunerated membership: EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD. All other authors have declared no conflicts of interest.