Results of the prospective phase 2 ATLANT study indicate that lanreotide autogel (LAN) plus temozolomide (TMZ) combination therapy was efficacious and well-tolerated in patients with progressive thoracic neuroendocrine tumors (NETs).
The ATLANT study was a prospective, 12-month, multicenter, single-arm, open-label phase 2 pilot study that evaluated the safety and efficacy outcomes of LAN + TMZ combination therapy in patients with progressive thoracic NETs; study results were reported at the European Society for Medical Oncology Virtual Congress 2020.
Eligible patients enrolled from 13 third-level Italian NET centers had unresectable; locally advanced or metastatic; well- or moderately differentiated NETs of the lung or thymus (typical or atypical carcinoid) with imaging progression documented in the previous 12 months, and World Health Organization performance status ≤2. Patients were administered subcutaneous LAN 120 mg in combination with oral TMZ 250 mg over 5 days every 28 days. The primary end point was disease control rate (DCR) at 9 months, with ≥30% deemed clinically relevant and ≤10% unacceptable. Secondary end points included progression-free survival, time to progression, duration of response, best overall response, overall response rate at 9 and 12 months, and DCR at 12 months.
A total of 40 patients were enrolled in the study; the majority of patients were male (60%), with a mean (standard deviation) age of 64.9 years and lung as primary tumor sites (90%). The majority of tumors had a mitotic count (mitoses/2 mm2) <2 (30%) or ≥2 to <10 (42.5%) and Ki67 expression 4 to <25% (80%). In terms of TNM staging, 46.2% of primary tumors were staged as T0, 7.7% as T1, 12.8% as T2, 10.3% as T3, and 17.9% as T4.
The investigator-assessed DCR at 9 months in the intent-to-treat population was 35.0% (95% confidence interval [CI], 20.63-51.68), which included 1 partial response and 13 stable disease; the DCR achieved (35.0%) was significantly higher than the prespecified 10% (P <.0001) but not superior to 30% (P = .297). Using investigator assessments between 7.5 months and 10.5 months, the DCR was 45% (95% CI, 29.26-61.51), which was significantly higher than 10% (P <.0001) and 30% (P = .0320). Median progression-free survival was 37.1 weeks (95% CI, 24.1-52.9).
Treatment-emergent adverse events (TEAEs) were reported in 97.5% of patients, the majority of which were grade 1/2. Grade 3 TEAEs were reported in 30% of patients, and grade 4 in 10%; 2 deaths occurred. Nine (22.5%) patients experienced serious TEAEs, of which 2 were treatment-related. Two TEAEs led to withdrawal of study treatment, 13 led to interruption of study medication, and 1 led to dose reductions. The safety profile of the combination was consistent with previously described drug profiles of LAN and TMZ. The most common TEAEs included nausea (52.5%), vomiting (32.5%), diarrhea (30.0%), constipation (20%), and asthenia (20%).
Based on the results of this prospective study, it was concluded that the LAN and TMZ combination was generally well-tolerated and efficacious, and may represent a treatment option for the management of progressive thoracic NETs.
Source: Ferolla P, et al. Ann Oncol. 2020;31(suppl 4). Abstract 1161MO.
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