Combination Therapy for Advanced Lung and Thymus Carcinoids
A European phase II trial has shown activity of long-acting pasireotide, everolimus (Afinitor), or their combination in patients with advanced lung and thymus carcinoids. These study findings were reported by Ferolla et al in The Lancet Oncology.
Study Details
In the study, 124 patients from 36 sites in 9 countries with unresectable or metastatic well-differentiated carcinoid tumors of the lung or thymus and radiologic disease progression within the prior 12 months were randomized between August 2013 and September 2014 to receive long-acting pasireotide at 60 mg intramuscularly every 28 days (n = 41), everolimus at 10 mg once daily (n = 42), or the combination (n = 41) for 12 months. Overall, 93% to 95% of patients across the groups had a carcinoid of the lung.
The primary endpoint was the proportion of patients who were progression free (complete or partial response or stable disease) at 9 months. The minimum number of patients required to be progression free at month 9 to consider the treatment effective was 13 in the pasireotide group, 14 in the everolimus group, and 13 in the combination group.
9-Month Outcome
At 9 months, the proportions of patients who were progression free were 39.0% (n = 16) in the long-acting pasireotide group, 33.3% (n = 14) in the everolimus group, and 58.5% (n = 24) in the combination group. No patients had a complete response, and partial response was observed in one patient in each group.
Adverse Events
The most common grade 3 or 4 adverse events suspected to be related to treatment were increased γ-glutamyltransferase (10%), diarrhea (7%), and hyperglycemia (7%) in the long-acting pasireotide group; hyperglycemia (17%), stomatitis (10%), and diarrhea (7%) in the everolimus group; and hyperglycemia (22%) and diarrhea (10%) in the combination group. Three deaths during or up to 56 days after the 12-month treatment phase were suspected to be related to everolimus: one in the everolimus group due to acute kidney injury associated with diarrhea, and two in the combination group, associated with diarrhea and urinary sepsis in one patient and acute renal failure and respiratory failure in one patient.
The investigators concluded: “The study met the primary endpoint in all three treatment groups. Safety profiles were consistent with the known safety profiles of these agents. Further studies are needed to confirm the antitumour efficacy of the combination of a somatostatin analogue with everolimus in lung and thymic carcinoids.”
The study was funded by Novartis Pharma AG.
Piero Ferolla, MD, of the Multidisciplinary NET Group, Umbria Regional Cancer Network and the University of Perugia, is the corresponding author of The Lancet Oncology article.
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