NANETS2022 15th Annual Multidisciplinary NET Medical Symposium NANETS 2022 Clinical – Chemo/SSA/Biologics (13 abstracts)
Progression-Free Survival in Patients with Bronchopulmonary Neuroendocrine Tumors Treated with Lanreotide or Placebo: Adjustment for Crossover Effects in Placebo Arm
Simron Singh 1,2 , Wieneke Buikhuisen 3 , Jaume Capdevila 4 , Martyn E Caplin 5 , Christian Grohe 6 , Dieter Hörsch 7 , Markus Raderer 8 , Diane Reidy-Lagunes 9 , Edward M Wolin 10 , Christelle Pommie 11 , Xuan Mai Truong 11 & Eric Baudin 12
1Division of Medical Oncology, University of Toronto; 2Sunnybrook Odette Cancer Center, Sunnybrook HSC, Toronto, Ontario, Canada; 3Department of Thorax Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; 4Medical Oncology Department, Vall d'Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), IOB Quirón-Teknon, Barcelona, Spain; 5Neuroendocrine Tumour Unit, Royal Free Hospital School of Medicine, London, UK; 6Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin, Germany; 7ENETS Centre of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany; 8Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; 9Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, NY, USA; 10Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 11Ipsen, Boulogne-Billancourt, France; 12Endocrine Oncology Unit, Gustave Roussy, Villejuif, France.
Background: SPINET was a phase 3 trial (NCT02683941) in patients with well-differentiated, advanced bronchopulmonary neuroendocrine tumors (NETs; typical and atypical carcinoids [TCs and ACs]). During the double-blind (DB) period, patients were randomized (2:1) to receive lanreotide autogel/depot (LAN; 120 mg) or placebo (PBO) every 28 days; in the optional open-label (OL) phase, all patients received LAN. Recruitment was stopped early due to slow accrual; all eligible patients transitioned to OL-LAN. The adapted primary endpoint was centrally confirmed progression-free survival (PFS) during the DB or OL phases in patients randomized to LAN. The aim of this post hoc analysis was to compare PFS data during the DB and OL phases between PBO and LAN, adjusting for the crossover using the rank-preserving structural failure time (RPSFT) model.
Methods: RPSFT is one of the most common statistical methods used to adjust overall survival (OS) data for crossover in oncology trials (Jack Ishak K et al. Pharmacoeconomics 2014;32:533; Bennett I et al. Value Health 2018;21:105) and has been used previously in a post hoc analysis of a phase 3 study in pancreatic NETs (Faivre S et al. Ann Oncol 2017;28:339). RPSFT is a non-parametric model that provides a treatment-effect estimate that is corrected for the confounding effect of crossover. Kaplan-Meier estimates were generated and the hazard ratio (HR) estimated using the multivariate Cox proportional-hazards model, stratified for tumor subtype.
Results: Overall, 77 patients were randomized; this analysis accounted for the 19/26 patients in the PBO arm (73%) who transitioned to OL-LAN. Over the DB+OL-LAN phase, median (95% CI) centrally assessed PFS based on RPSFT was 13.5 (11.0; not calculable [NC]) months for PBO and 16.6 (11.3; 21.9) months for LAN (HR [95% CI]: 0.78 [0.48; 1.52]; P=0.601). Data by NET subtype are shown in the table.
| LAN (observed; DB+OL) | PBO (with RPSFT) | HR (95% CI) | |
| All patients | 16.6 (11.3; 21.9) [n=50] | 13.5 (11.0; NC) [n=26] | 0.78 (0.48; 1.52) P=0.601 |
| TCs | 21.9 (12.8; NC) [n=28] | 13.9 (13.4; NC) [n=16] | – |
| ACs | 13.8 (5.4; 16.6) [n=22] | 11.0 (2.8; 16.9) [n=10] | – |
Conclusions: The risk of disease progression or death was lower with LAN vs PBO in patients with advanced, well-differentiated bronchopulmonary NETs (HR=0.78). However, despite adjusting for PBO crossover, the HR 95% CI included 1.00, reflecting the lack of statistical significance in this small sample. LAN may provide some clinical activity for TCs.
Abstract ID 21377
Volume 89
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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