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

Introduction: 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. Methods: 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: disease control rate (DCR) at 9 months (primary; investigator-assessed), median progression-free survival (PFS), biomarkers and safety. Results: Patients: n=40; 60% male. Primary tumor site: lung (90%); thymus (10%). Carcinoid type: typical (20.0%), atypical (52.5%). DCR at 9 months was 35.0% (95% confidence interval [CI] 20.63–51.68) (non-acceptability 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. Conclusions: This study showed that 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

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

Introduction: 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. Methods: 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: disease control rate (DCR) at 9 months (primary; investigator-assessed), median progression-free survival (PFS), biomarkers and safety. Results: Patients: n=40; 60% male. Primary tumor site: lung (90%); thymus (10%). Carcinoid type: typical (20.0%), atypical (52.5%). DCR at 9 months was 35.0% (95% confidence interval [CI] 20.63–51.68) (non-acceptability 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. Conclusions: This study showed that 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