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 Vaccaro, Charles Blanke

Research output: Contribution to journalArticle

35 Citations (Scopus)

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. Cancer 2015;121:2193-2197.

Original languageEnglish (US)
Pages (from-to)2193-2197
Number of pages5
JournalCancer
Volume121
Issue number13
DOIs
StatePublished - Jul 1 2015

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Esophagogastric Junction
Stomach
Survival
Neoplasms
Exanthema
Hyperglycemia
Fatigue
Anemia
Diarrhea
Confidence Intervals
Therapeutics
Anorexia
Heart Arrest
Respiratory Insufficiency
Nausea
Disease-Free Survival
Vomiting
Fasting
Heart Failure
MK 2206

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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). / 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; Blanke, Charles.

In: Cancer, Vol. 121, No. 13, 01.07.2015, p. 2193-2197.

Research output: Contribution to journalArticle

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 ; Blanke, Charles. / 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). In: Cancer. 2015 ; Vol. 121, No. 13. pp. 2193-2197.
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title = "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)",
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. Cancer 2015;121:2193-2197.",
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author = "Ramanathan, {Ramesh K.} and McDonough, {Shannon L.} and Kennecke, {Hagen F.} and Syma Iqbal and Baranda, {Joaquina C.} and Seery, {Tara E.} and Lim, {Howard J.} and Hezel, {Aram F.} and Gina Vaccaro and Charles Blanke",
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T1 - Phase 2 study of MK-2206, an allosteric inhibitor of AKT, as second-line therapy for advanced gastric and gastroesophageal junction cancer

T2 - A SWOG cooperative group trial (S1005)

AU - Ramanathan, Ramesh K.

AU - McDonough, Shannon L.

AU - Kennecke, Hagen F.

AU - Iqbal, Syma

AU - Baranda, Joaquina C.

AU - Seery, Tara E.

AU - Lim, Howard J.

AU - Hezel, Aram F.

AU - Vaccaro, Gina

AU - Blanke, Charles

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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. Cancer 2015;121:2193-2197.

AB - 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. Cancer 2015;121:2193-2197.

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