1161MO - Lanreotide autogel (LAN) and temozolomide (TMZ) combination therapy in progressive thoracic neuroendocrine tumours (TNETs): ATLANT study results

Background

LAN and TMZ are among the main therapies recommended for progressive TNETs but prospective data are lacking. We present safety and efficacy outcomes of this combination in progressive TNETs.

Methods

ATLANT was a 12-month, phase II, multicentre, single-arm, open-label study. Eligible patients had unresectable, locally advanced or metastatic, well-differentiated TNETs (bronchial or thymic, typical or atypical carcinoid) with baseline radiological progression (RECIST v1.1) in the previous 12 months. Patients received subcutaneous LAN 120 mg and oral TMZ 250 mg/day over 5 days, every 28 days. Primary endpoint: disease control rate (DCR) at 9 months (RECIST v1.1 complete response, partial response or stable disease [clinically relevant: ≥30%, unacceptable: ≤10%]). Data were analysed using exact binomial proportion tests for one-way tables.

Results

Patients (N=40; 60% male) had a mean (SD) age of 64.9 (11.8) years. The primary tumour site was: lung, 90%; thymus, 10% (typical, 20.0%; atypical, 52.5%; carcinoid, 27.5%). Mitotic count (mitoses/2 mm²): <2: 30%; ≥2–<10: 42.5%; ≥10: 2.5%; not done: 25%. Ki-67 expression (N=20): <4%: 10%; 4–<25%: 80%; ≥25%: 10%. TNM staging: primary tumour TX: 5.1%, T0: 46.2%, T1: 7.7%, T2: 12.8%, T3: 10.3%, T4: 17.9%; regional lymph node N0: 56.4%, N1: 2.6%, N2: 23.1%, N3: 17.9%; distant metastasis M0: 5.1%, M1: 94.9%. Locally assessed DCR at 9 months (ITT population; N=40) was 35.0% (95% CI: 20.63; 51.68) (significantly higher than 10% p<0.0001 but not superior to 30% p=0.297). Median progression-free survival was 37.1 (95% CI: 24.1; 52.9) weeks. In total, 97.5% of patients had treatment-emergent adverse events (TEAEs; >90% of TEAEs were Grade 1/2), 9 (22.5%) patients had serious TEAEs (of which 2 were treatment related), 2 TEAEs led to withdrawal of study treatment, and 2 led to death. The observed TEAEs were in line with the known individual drug profiles, and there were no new or unexpected AEs. Most common TEAEs included nausea (52.5%), vomiting (32.5%) and diarrhoea (30.0%).

Conclusions

These results suggest that the LAN and TMZ combination was generally well tolerated and could be an effective regimen for managing progressive TNETs.

Clinical trial identification

NCT02698410; EudraCT: 2014-005579-10.

Editorial acknowledgement

Cara Valvona, PhD, on behalf of Watermeadow Medical, an Ashfield company, provided medical writing support, which was funded by the study sponsor in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

P. Ferolla: Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono. A. Berruti: Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. F. Spada: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck. M.P. Brizzi: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Celgene. T. Ibrahim: Advisory/Consultancy: Eisai; Research grant/Funding (institution): Novartis. A. Colao: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen. A. Faggiano: Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Novartis. D. Giuffrida: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: Ipsen; Speaker Bureau/Expert testimony: Pfizer; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Roche. S. Ghizzoni: Full/Part-time employment: Ipsen. A. Houchard: Full/Part-time employment: Ipsen. N. Fazio: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy: Advanced Accelerator Applications; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.