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)

作者：Ramanathan Ramesh K^*; McDonough Shannon L; Kennecke Hagen F; Iqbal Syma; Baranda Joaquina C; Seery Tara E; Lim Howard J; Hezel Aram F; Vaccaro Gina M; Blanke Charles D

来源：Cancer, 2015, 121(13): 2193-2197.

DOI：10.1002/cncr.29363

• AKT inhibitor
• gastric cancer
• gastroesophageal junction
• MK-2206
• phase 2 study

BACKGROUNDThe AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers.
METHODSPatients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level150 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.
RESULTSSeventy 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)
CONCLUSIONSMK-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. Cancer 2015;121:2193-2197.

• 出版日期2015-7-1