Phase 2 study of MK-2206, an allosteric inhibitor of AKT, as second-line therapy for advanced gastric and gastroesophageal junction cancer: A SWOG cooperative group trial (S1005)
Ramesh K Ramanathan, Shannon L McDonough, Hagen F Kennecke, Syma Iqbal, Joaquina C Baranda, Tara E Seery, Howard J Lim, Aram F Hezel, Gina M Vaccaro, Charles D Blanke, Ramesh K Ramanathan, Shannon L McDonough, Hagen F Kennecke, Syma Iqbal, Joaquina C Baranda, Tara E Seery, Howard J Lim, Aram F Hezel, Gina M Vaccaro, Charles D Blanke
Abstract
Background: The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers.
Methods: Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation.
Results: Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4-86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7-1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7-9.4 months)
Conclusions: MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population.
Trial registration: ClinicalTrials.gov NCT01260701.
Keywords: AKT inhibitor; MK-2206; gastric cancer; gastroesophageal junction; phase 2 study.
Conflict of interest statement
CONFLICT OF INTEREST DISCLOSURES
The remaining authors have no conflicts of interest to declare.
© 2015 American Cancer Society.
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Source: PubMed