A phase II study of MK-2206, an allosteric inhibitor of AKT as second-line therapy for advanced gastric and gastroesophageal junction (GEJ) cancer: A SWOG Cooperative Group trial (S1005).
Bibliographic record
Abstract
4041 Background: The PI3K/AKT/MTOR pathway is frequently activated in gastric/GEJ cancers. This study evaluated the activity of single agent MK-2206 at the dose of 60 mg every other day in this tumor type. Methods: Eligible patients (pts) had gastric /GEJ adenocarcinoma with measurable disease, who had had progression after first-line treatment, or recurrence within six months after adjuvant therapy. Other pertinent eligibility criteria included a Zubrod performance status of 0-1, a fasting serum glucose ≤150 mg/dL, and < Grade 2 malabsorption or chronic diarrhea. Adequate hematologic, renal, hepatic, and cardiac function were required. Prior treatment with a PI3, AKT, or mTOR inhibitor was not allowed. MK-2206 (60 mg every other day) was given until progression or intolerable toxicity. Primary endpoint was overall survival (OS), secondary endpoints were safety, progression free survival (PFS) and response rate (RR). The study required 60 evaluable pts and a median OS of 6.5 months (mo) (power of 89%, significance level 0.07) to be considered encouraging for further investigation. Results: Seventy-five pts were enrolled between 1/1/11 to 5/1/13. Eight pts were ineligible and one pt withdrew; 66 pts were included in the analyses. Median age is 60.7 yrs (range 30.4-86.7), Males 70%, White 89% and Asian 6%. There were 2 deaths possibly related to study drug (cardiac arrest and respiratory failure). Gr 4 adverse events (AEs) were hyperglycemia, anemia and lung infection (1 each). Gr 3 AEs were infrequent and < 5% except for fatigue (6%). Other all Gr AEs included anemia 15%, anorexia 27%, diarrhea 24%, fatigue 48%, hyperglycemia 29%, nausea 40%, vomiting 20%, maculopapular rash 30%, and acneiform rash 8%. The RR is 2%, median PFS is 1.8 mo. (95% CI of 1.7- 1.8) and median OS is 5 mo (95% CI 4 - 10 mo). Conclusions: MK-2206 as 2nd line therapy in an unselected group of gastric/GEJ cancers was well tolerated with some evidence of activity (RR 2%, OS 5.0 mo) and in the range of other second line agents (irinotecan, docetaxel, ramucirumab). The primary study endpoint of 6.5 mo was not met. (Support: NIH/NCI cooperative group grants CA32102 and CA38926). Clinical trial information: NCT01260701.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".