ESMO 2016: Clinical Benefit Demonstrated With Everolimus and Pasireotide LAR Alone or in Combination in Advanced Lung and Thymic Carcinoids
In patients with advanced lung or thymus carcinoid receiving everolimus, pasireotide LAR, or the combination of the two drugs, statistically significant positive impact was seen on proportion of patients’ progression-free rate at 9 months (primary endpoint) in all three arms, more relevant in the combination arm, according to phase II study findings presented by Ferolla et al at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark (Abstract 416O).
Activity of Everolimus and Pasireotide LAR
Everolimus has shown clinical benefit in a variety of cancer types, including neuroendocrine tumours (NETs), by blocking the mTOR pathway, while pasireotide LAR is a somatostatin analogue.
Piero Ferolla, MD, of the Multidisciplinary NET Group and the Department of Medical Oncology, Umbria Regional Cancer Network and University of Perugia in Perugia, Italy, and the co-investigators pointed out that on the basis of the current ESMO and European Neuroendocrine Tumor Society (ENETS) guidelines, advanced carcinoid of the lung or thymus remains an area of high unmet medical need with few treatment options. No previous study was entirely focused on these tumors. Dr. Ferolla underlines that everolimus showed improved progression-free survival in the phase III RADIANT-4 study in patients with gastrointestinal or lung NETs, and that pasireotide LAR has demonstrated potential antitumor activity in patients with NETs. These observations prompted Dr. Ferolla and colleagues to assess the efficacy and safety of pasireotide LAR and everolimus alone and in combination in patients with progressive carcinoids of lung and thymus.
LUNA Trial
The phase II LUNA trial randomly assigned 41 patients to pasireotide LAR at 60 mg/month intramuscular, 42 patients to oral everolimus at 10 mg/day orally, and 41 patients to pasireotide LAR plus everolimus at the same single-agent doses.
The primary endpoint of the trial was the progression-free rate at 9 months, defined as the proportion of patients with documented complete response, partial response, or stable disease by RECIST v.1.1 criteria at 9 months. Secondary endpoints included progression-free survival, disease control rate, and safety.
Patients had a median age of 64 years. Atypical carcinoid was present in 68.5% of patients, while 31.5% of the patients had typical carcinoid. Primary tumor site was the lung in 93.5% of patients and thymus in 6.5%. World Health Organization (WHO) performance status was 0, 1, or 2 in 64%, 34%, and 2% of patients, respectively. Prior drug treatment had been administered to 44% of patients; radiotherapy to 27%; surgery/locoregional therapy to 97%; and 48% of patients had received prior somatostatin analogues.
Primary Endpoint Reached
The trial’s primary endpoint, progression-free rate at 9 months, was achieved by 39.0% of patients on single-agent pasireotide LAR (95% confidence interval [CI] = 24.2–55.5), 33.3% of patients on sole everolimus (95% CI = 19.6–49.5), and by 58.5% of patients on combined everolimus and pasireotide LAR (95% CI = 42.1–73.7).
Complete response was not observed in any of the three treatment groups. The best overall response at 9 months was partial response, which was achieved by 2% of patients in each treatment arm. Stable disease was attained by 34% of pasireotide LAR patients, 31% of everolimus patients, and by 49% of patients receiving the combination. Progressive disease occurred in 17% receiving pasireotide LAR vs 2% of patients receiving everolimus. None of the patients receiving the combined treatment reported progressive disease.
Study treatment was discontinued by 65% of patients during the 12-month core phase of treatment. Discontinuation due to progressive disease or adverse events was each reported in 27% of patients. Adverse events were mostly grades 1/2 across treatment groups. The most common adverse events (any grade) with combined pasireotide LAR and everolimus were hyperglycaemia, which was reported by 88% of patients, diarrhea in 78%, weight decrease in 56%, asthenia in 37%, and stomatitis in 34%.
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