421PD - Impact of prior therapies on everolimus treatment in the subgroup of patients with advanced lung neuroendocrine tumors (NET) in the RADIANT-4 trial

Date 10 October 2016
Event ESMO 2016 Congress
Session Endocrine and neuroendocrine tumours
Topics Neuroendocrine Tumours
Presenter Roberto Buzzoni
Citation Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369
Authors R. Buzzoni1, G.D. Fave2, J. Strosberg3, M. Voi4, A. Ridolfi5, L. Bubuteishvili-Pacaud6, F. Herbst7, E. Wolin8, N. Fazio9
  • 1Department Of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Medical Oncology, Azienda Ospedaliera St. Andrea - Roma, Roma/IT
  • 3Department Of Medicine, Moffitt Cancer Center, Tampa/US
  • 4Ogd Ocd, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 5Oncology, Novartis Pharma S.A.S., Rueil-Malmaison/FR
  • 6Clinical Research, Novartis Pharma AG, Basel/CH
  • 7Medical Affairs, Novartis Pharma AG, Basel/CH
  • 8Department Of Medical Oncology, Montifiore Einstein Center for Cancer Care, Bronx/US
  • 9Unit Of Gastrointestinal Medical Oncology And Neuroendocrine Tumors, Istituto Europeo di Oncologia, 20141 - Milano/IT

Abstract

Background

Treatment paradigms in lung NET have conventionally relied on therapies such as chemotherapy, radiotherapy and somatostatin analogs (SSA) although evidence from randomized clinical trials remains limited. In the recent subgroup analysis of a large, phase 3, RADIANT-4 study everolimus (EVE), an mTOR inhibitor showed clinically meaningful 6-month improvement in PFS [EVE vs placebo (PBO): 9.2 (6.8-10.9) vs 3.6 (1.9-5.1) mos] and reduced tumor progression risk by 50% (HR, 0.50; 95% CI, 0.28-0.88) in patients with advanced, progressive, nonfunctional lung NET compared to PBO (Fazio et al. 2016 ENETS). This post-hoc analysis evaluates the impact of prior-therapies on EVE treatment in lung NET patients from the RADIANT-4 study.

Methods

Patients with advanced non-functional lung or GI NET were randomized (2:1) to EVE 10 mg/d or PBO, both with best supportive care. Subgroups of patients who received SSA, chemo-, radio- or no prior therapy within the lung NET subgroup were analyzed.

Results

Of the 90 patients with lung NET enrolled in the RADIANT-4 study; 63 patients were randomized to the EVE arm and 27 patients to the PBO arm. Median age, 65 years; males: 52%; most pts (99%) had well-differentiated disease; Caucasian: 86%; WHO PS 0/1/2: 71%/28%/1%. Prior therapies (EVE vs PBO) included: SSA (mostly for tumor growth control; 43% vs 41%), radiotherapy including peptide receptor radionuclide therapy (PRRT; 40% vs 48%), chemotherapy (40% vs 48%) and no prior therapy (14% vs 11%). Median PFS in the subgroups of patients receiving each of the prior-therapies is listed in the Table. The most common drug-related adverse events (AEs; ≥ 30% incidence in either arm for the whole lung subgroup) were stomatitis, rash and fatigue.

Prior-therapies EVE Median PFS, mos (95% CI) PBO Median PFS, mos (95% CI)
Chemotherapy 8.5 (5.6,11.7) 2.9 (1.8,3.7)
Radiotherapy* 9.2 (5.7,NE) 3.0 (1.9,5.1)
SSA therapy 9.5 (6.0,11.7) 3.7 (1.0,11.2)
No prior therapy 9.7 (0.9,NE) 3.6 (1.7,NE)

*Includes PRRT

Conclusions

EVE showed PFS benefit in patients with advanced lung NET regardless of prior-therapies, consistently with the overall RADIANT-4 study. No prior-therapy specific safety signal was seen in any of the subgroups.

Clinical trial identification

NCT01524783

Legal entity responsible for the study

Novartis Pharmaceuticals

Funding

Novartis Pharmaceuticals

Disclosure

R. Buzzoni: Grants and non-financial support from Novartis, grants from Otsuka, grants and non-financial support from Italfarmaco, non-financial support from Ipsen, during the conduct of the study.

J. Strosberg: Grants and personal fees from Novartis, grants from Pfizer, personal fees from Bayer, Genentech, during the conduct of the study; personal fees from Ipsen, Lexicon, Novartis, outside the submitted work.

M. Voi, A. Ridolfi, L. Bubuteishvili-Pacaud: Employment- Novartis.

F. Herbst: Employment- Novartis, Stock options- Novartis.

E. Wolin: Advisory Board- Advanced accelerator applications.

N. Fazio: Grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from Ipsen, during the conduct of the study; personal fees from Italfarmaco, Ipsen, Lexicon, outside the submitted work .

All other authors have declared no conflicts of interest.