Progression-free survival (PFS) and subgroups analyses of lenvatinib in patients (pts) with G1/G2 advanced pancreatic (panNETs) and gastrointestinal (giNETs) neuroendocrine tumors (NETs): Updated results from the phase II TALENT trial (GETNE 1509).

Authors

Jaume Capdevila

Jaume Capdevila

Medical Oncology Department, Vall d’Hebron University Hospital; Vall d’Hebron Institute of Oncology (VHIO)., Barcelona, Spain

Jaume Capdevila , Nicola Fazio , Carlos López-López , Alexandre 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 , Toni Ibrahim

Organizations

Medical Oncology Department, Vall d’Hebron University Hospital; Vall d’Hebron Institute of Oncology (VHIO)., Barcelona, Spain, European Institute of Oncology, Milan, Italy, Marqués de Valdecilla University Hospital, Santander, Spain, Hereditary Cancer Program, Catalan Institute of Oncology, Barcelona, Spain, The Christie NHS Foundation Trust, Manchester, United Kingdom, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy, Hospital Universitario La Paz, Madrid, Spain, Beatson Oncology Centre, Glasgow, United Kingdom, University Hospital, Vienna, Austria, MD Anderson Cancer Center, Madrid, Spain, Hospital Universitario, Madrid, Spain, Hospital Universitario Central de Asturias, Oviedo, 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

Research Funding

Pharmaceutical/Biotech Company

Background: Pts with advanced G1/G2 NETs have limited treatment options with overall response rates (ORR) with targeted agents (TA) < 10%. Benefit on PFS after TA therapy has not been demonstrated. The mechanism of action of lenvatinib (VEGFR1-3 & FGFR1-4 inhibitor) may increase efficacy and revert primary and acquired resistance to TA. We report the updated results on PFS, safety and subgroups. Methods: This prospective phase II study had two cohorts: G1/G2 panNETs and giNETs. All pts had baseline documented disease progression (PD) by RECIST. For panNETs, PD to TA was mandatory, regardless 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 ORR by central radiology review. PFS was calculated by investigator assessment. Biochemical responses were defined as reduction from baseline > 50%. 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/56 giNETs). Prior therapies were CHT 32%, SSAs 87%, everolimus (E) 70% and sunitinib (S) 30% for panNETs. ORR was 29%, 40% for panNETs and 18.5% for giNETs. With a median follow-up of 17 months (m), PFS for panNETs was 15.8 m (95% CI 11.4-NR) and 15.4 m (95% CI 11.5-19.5) for giNETs. Dose reductions/interruptions were needed in 91.8% with a median dose of 20 mg qd. In the subgroups analyses, all pts obtained the same benefit in PFS and ORR, including grade and prior therapy with S (PFS: 16.4 m, ORR: 43.7%) or E (PFS: 15 m, ORR: 37.1%) (p = ns). A significant correlation of chromogranin A decrease and prolonged PFS in giNETs (17.6 m vs NR, p = 0.032) was observed. The most frequent G3-4 adverse events were hypertension (20.7%), asthenia (13.5%), diarrhea (7.2%) and abdominal pain (5.4%). Conclusions: Lenvatinib showed the highest reported ORR with a TA by central radiology assessment in panNETs and giNETs with promising PFS in a pretreated population. The benefit was observed across subgroups analyses, including pretreated pts with TA. Clinical trial information: NCT02678780

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Abstract Details

Meeting

2019 Gastrointestinal Cancers Symposium

Session Type

Poster Walks

Session Title

Poster Walks: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Sub Track

Multidisciplinary Treatment

Clinical Trial Registration Number

NCT02678780

Citation

J Clin Oncol 37, 2019 (suppl 4; abstr 332)

DOI

10.1200/JCO.2019.37.4_suppl.332

Abstract #

332

Poster Bd #

H10

Abstract Disclosures