Final results of the TALENT trial (GETNE1509): a prospective multicohort phase II study of lenvatinib in patients (pts) with G1/G2 advanced pancreatic (panNETs) and gastrointestinal (giNETs) neuroendocrine tumors (NETs).

Jaume Capdevila Medical Oncology Department, Vall d’Hebron University Hospital; Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain info_outline Jaume Capdevila, Nicola Fazio, Carlos Lopez Lopez, Alex Teule, Juan W. Valle, Salvatore Tafuto, Ana B. Custodio, Nicholas Reed, Markus Raderer, Enrique Grande, Rocio Garcia-Carbonero, Paula Jiménez-Fonseca, Vicente Alonso, Lorenzo Antonuzzo, Andrea Spallanzani, Alfredo Berruti, Isabel Sevilla, Adelaida La Casta Munoa, Jorge Hernando-Cubero, Toni Ibrahim

Authors Jaume Capdevila Medical Oncology Department, Vall d’Hebron University Hospital; Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain info_outline Jaume Capdevila, Nicola Fazio, Carlos Lopez Lopez, Alex Teule, Juan W. Valle, Salvatore Tafuto, Ana B. Custodio, Nicholas Reed, Markus Raderer, Enrique Grande, Rocio Garcia-Carbonero, Paula Jiménez-Fonseca, Vicente Alonso, Lorenzo Antonuzzo, Andrea Spallanzani, Alfredo Berruti, Isabel Sevilla, Adelaida La Casta Munoa, Jorge Hernando-Cubero, Toni Ibrahim Organizations Medical Oncology Department, Vall d’Hebron University Hospital; Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, European Institute of Oncology, IRCCS, Milan, Italy, Department of Medical Oncology, H. Marques de Valdecilla, Santander, Spain, Institut Català d’Oncologia, L’Hospitalet, Barcelona, Spain, University of Manchester/The Christie, Manchester, United Kingdom, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy, Hospital Universitario La Paz, Madrid, Spain, Beatson Oncology Centre, Glasgow, United Kingdom, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, MD Anderson Cancer Center Madrid, Madrid, Spain, 12 de Octubre University Hospital, Madrid, Spain, Hospital Universitario Central de Asturias, Asturias, Spain, Medical Oncology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain, Careggi University Hospital, Florence, Italy, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy, Medical Oncology, University of Brescia, Spedali Civili Hospital, Brescia, Italy, Hospital Universitario Virgen de la Victoria, Málaga, Spain, Hospital Universitario Donostia, San Sebastian, Spain, Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), Bracelona, Spain, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Approved systemic therapies for advanced NETs have showed limited tumor shrinkage and no data of activity after progression to prior targeted agents (TA) is available. Lenvatinib, a potent VEGFR1-3 & FGFR1-4 inhibitor may increase efficacy and revert primary and acquired resistance to TA. We report the final results of the TALENT trial. Methods: Two independent cohorts were included: panNETs and giNETs. All pts had baseline documented progression disease (PD) by RECIST. For panNETs, PD to TA was mandatory, regardless of prior therapy with somatostatin analogs (SSAs) or chemotherapy (CHT); and for giNETs, PD on SSAs. Pts were treated with lenvatinib at 24 mg qd until PD or intolerable toxicity. The primary endpoint was overall response rate (ORR) by central radiology review. Progression-free (PFS) and overall survival (OS) were assessed by investigator. With 55 pts per arm, our study was powered to identify an ORR ≥25% (90% power, 5% α-error). Results: We recruited 111 pts: 55 panNETs and 56 giNETs (78% from small intestine). Prior therapies were CHT 32%, SSAs 87%, everolimus 70% and sunitinib 30% for panNETs. ORR was 29%, 42.3% for panNETs and 16.3% for giNETs. With a median follow-up of 19 m, PFS and OS for panNETs were 15.5 m (95% CI 11.3-not reached (NR)) and 29.2 m (95% CI 23.2-NR); and 15.4 m (95% CI 11.5-19.4) and NR for giNETs, respectively. Pts who obtained a response by RECIST had a significantly better PFS compared with non-responders (NR vs 11.2 m in panNETs (p=0.004); 37.2 m vs 14.9 m in giNETs (p=0.005). In the subgroup analyses, all pts obtained the same benefit in PFS and ORR, including tumor grade, prior therapies, hormone release, primary location and tumor burden. The most frequent G3/4 adverse events were hypertension (22%), fatigue (11%) and diarrhea (11%). Dose reductions/interruptions were needed in 91.8% with a median dose of 20 mg qd. Conclusions: To our knowledge, we report the highest ORR by central radiology assessment with a TA in this setting. Lenvatinib showed a promising PFS and OS in a pretreated population with benefit across subgroups. Further development in advanced NETs is warranted. Clinical trial information: NCT02678780