Published August 31, 2022
0 views Journal article

Efficacy and Safety of Lanreotide Autogel and Temozolomide Combination Therapy in Progressive Thoracic Neuroendocrine Tumors (Carcinoid): Results from the Phase 2 ATLANT Study.

Creators

  • 1. Multidisciplinary NET Center, Umbria Regional Cancer Network, Perugia, Italy.
  • 2. Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST-Spedali Civili, Brescia, Italy.
  • 3. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, IEO, Milan, Italy.
  • 4. Scientific Institute for Research, Hospitalization and Healthcare
  • 5. Department of Oncology, Medical Oncology, A.O.U. San Luigi Gonzaga, Turin, Italy.
  • 6. Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST), "Dino Amadori", Meldola, Italy.
  • 7. Department of Oncology 2, A.O.U. Pisana, Santa Chiara Hospital, Pisa, Italy.
  • 8. Department of Oncology, Istituto Oncologico del Mediterraneo, Viagrande (Catania), Italy.
  • 9. Medical Oncology 1, Regina Elena National Cancer Institute, IRCCS, Rome, Italy.
  • 10. Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Università Sapienza di Roma, Rome, Italy.
  • 11. Department of Clinical Medicine and Surgery and UNESCO Chair for Health Education and Sustainable Development, Università Federico II di Napoli, Naples, Italy.
  • 12. Department of Oncology, University of Turin, Turin, Italy.
  • 13. University of Turin
  • 14. Ipsen, Assago, Milan, Italy.
  • 15. Ipsen
  • 16. Ipsen, Boulogne-Billancourt, France.

Description

Lanreotide autogel (LAN) and temozolomide (TMZ) are guidelines-recommended monotherapies for thoracic neuroendocrine tumors (carcinoids; T-NETs), but prospective data for both combined and monotherapies are lacking. ATLANT (NCT02698410) evaluated efficacy and safety of LAN/TMZ in progressive T-NETs. ATLANT was a 12-month, Italian, phase 2, single-arm, open-label, multicenter pilot study. Eligible patients had unresectable, locally advanced/metastatic, well-/moderately differentiated T-NETs with radiological progression. Patients received subcutaneous LAN 120 mg every 28 days and oral TMZ 250 mg/day for 5 consecutive days every 28-day cycle. Main endpoints are disease control rate (DCR) at 9 months (primary; investigator-assessed), median progression-free survival (PFS), biomarkers, and safety. The number of patients was 40; 60% were male. Primary tumor site was lung (90%) and thymus (10%). Carcinoid type was typical (20.0%) and atypical (52.5%). DCR at 9 months was 35.0% (95% confidence interval (CI) 20.63-51.68; nonacceptability threshold ≤10%, p < 0.0001; not significantly above clinically relevant threshold ≥30%, p = 0.2968). DCR between 7.5 and 10.5 months (sensitivity analysis) was 45.0% (95% CI: 29.26-61.51) and clinically relevant (p = 0.0320 at ≥30% threshold). Median PFS was 37.1 (95% CI: 24.1-52.9) weeks. No association was observed between biomarker variations (chromogranin A, neuron-specific enolase, somatostatin receptor type-2, Ki-67, 6-O-methylguanine-DNA-methyl-transferase) and DCR or PFS. Most patients (97.5%) had treatment-emergent adverse events (TEAEs); 72.5% had treatment-related TEAEs. TEAEs were mainly grade 1/2. No unanticipated TEAEs were reported. This study showed that the LAN/TMZ combination has promising efficacy in progressive T-NETs, and was well tolerated. Larger studies are warranted to support the clinical benefits of LAN/TMZ in patients with T-NETs. © 2022 S. Karger AG, Basel.
Enabled by The Lens