Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)
Bibliographic record
Abstract
7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".