A phase II study of RAD001 (R) (everolimus) monotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Bibliographic record
Abstract
7589 Background: R is an oral inhibitor of mammalian target of rapamycin (mTOR) with anti-tumor activity. Single-agent R and in combination with other anticancer agents showed efficacy in in vitro and in vivo NSCLC models. In a phase I study, 4 disease stabilizations (SD) and 1 partial response (PR) were reported from 14 NSCLC pts treated with R monotherapy. Methods: Advanced NSCLC pts with adequate organ function, performance status ≤ 2, failing either ≤ 2 C (arm 1) or ≤ 2 C and an EGFR-I (arm 2) were treated with R at 10 mg qd if tolerable until progression (PD). Study applied a Simon-2-stage design with primary endpoint of objective tumor response rate (RR) according to RECIST. CT scans were performed every 28 days until month 4 and then every 2 months thereafter. Adverse events (AE) were assessed using NCI CTC v. 2.0. Results: This analysis is based on data acquired up to 20 Sep 2006. 85 pts were enrolled between 08/2005 and 05/2006. Demographics and patient disposition were (arm 1/arm 2): 42/43 (7 pts ongoing), female 38.1%/51.2%, never smoker 14.3%/44.2%, adenoca. 57.1%/62.8%, squamous cell ca. 21.4%/14.0%, BAC 2.4%/16.3%, others 19.1%/6.9%. Median age was 60 years (range 21–74). R was given on arm 1 as 2nd line therapy in 64.3% of pts., as 3rd line in 35.7% and on arm 2 as 3rd line in 58.1%, as 4th line in 41.9%. 90.6% pts had stage IV disease. The trial did not proceed to stage 2 based on RR for 74 pts in the efficacy population. Best overall tumor response (arm 1/2 in %): confirmed PR (5.3/2.8), SD (44.7/44.4); SD ≥ 12 weeks (34.2/41.7), duration of SD in days arm 1 (58 –267) and arm 2 (68 –231). Median PFS on arm 1 is 11.3 weeks (95% CI: 8.1; 12.4) and on arm 2 is 9.7 weeks (7.3; 13.0). Most frequent AEs (pts, all grades/grade 3 and 4): stomatitis/mucositis (43/5), cough (27/1), dyspnea (33/8), rash (26/0), fatigue (25/10), anorexia (25/1), nausea (20/0), anemia (18/3), epistaxis (18/0), diarrhea (17/2). Analyses of molecular markers in tumor tissue samples are ongoing. Conclusions: 10 mg qd R monotherapy is well tolerated and shows limited activity in pretreated advanced NSCLC pts. Combination trials with both standard chemotherapy and targeted agents are in progress. 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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".