A global, multicenter phase II trial of lapatinib plus capecitabine in gastric cancer.
Bibliographic record
Abstract
88 Background: Advanced gastric cancer (GC) is an incurable disease. HER2 overexpression has been reportedin 6%–35% of gastric and gastroesophageal tumors, whereas the EGFR is upregulated in about 18%–28%. Clinical studies confirm that targeting HER2 in combination with chemotherapy is an effective strategy, achieving a median survival of ∼13.5 mos. Lapatinib, a dual tyrosine kinase inhibitor of HER2 and the EGFR, inhibits tumor growth and modulates expression of fluoropyrimidine-targeting genes. LPT109747 is an international, multicenter phase II study investigating the combination of lapatinib + capecitabine in patients with advanced gastric or gastroesophageal junction adenocarcinoma. Methods: Primary endpoints of the study included clinical response rate, 5 mo PFS and mRNA and protein expression levels of genes involved in the 5-FU and HER2 pathway. HER2 overexpression was not required at study entry. Oral lapatinib was administered (1,250 mg/d, continuously) during a monotherapy run-in period (day -7 to 0) and in combination with oral capecitabine (1,000 mg/m 2 BID, 14 of 21 days). Patients were treated until disease progression (PD) or study withdrawal. Biopsies were performed on days -7 and 0. Safety was assessed every 3 weeks and response every 6 weeks by RECIST. Results: Sixty-seven patients were included in the current analysis: 25% female, 75% male; 51% Caucasian, 45% Asian; median age 60 y (range: 22-89 y); 75% GC, 25% GEJ. All 67 patients were evaluable for response. The overall response rate was 22.4% (16.4% confirmed). 45% of patients had stable disease, and 24% had PD. No complete responses were observed. PD or death at < 5 mo was 63%. At the time of data cut off, PFS at 5 mo was 28.4% (17.3%–40.5%); median follow up was 26.4 weeks (CI: 22.1; 55.9); 39% of patients remain in follow up. Most frequent grade 3/4 events were anemia (13%), hand-foot syndrome (12%), decreased appetite (10%), and nausea (9%). Conclusions: The combination of lapatinib + capecitabine shows promising efficacy and is well tolerated as 1st line treatment for advanced GC. An analysis of biomarker data may help identify who may benefit most from this regimen. [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 teacher head, 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".