Abstract 4660: A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small cell lung cancer.
Bibliographic record
Abstract
Abstract Tumor regrowth after chemotherapy may be driven by growth of tumor ‘stem cells’. Telomerase, required for indefinite replication, is upregulated in tumor progenitor cells. Imetelstat is a 13-mer oligonucleotide which is a potent and specific telomerase inhibitor. Progression-free survival (PFS) and the duration of responses after 1st-line chemotherapy for non-small-cell lung cancer (NSCLC) are short, which has led to an interest in developing active maintenance therapies. A randomized phase II study was conducted to assess whether imetelstat, given as maintenance therapy, prolongs PFS in NSCLC. Pts were eligible with advanced NSCLC not progressing after completing 4-6 cycles of platinum-based doublet induction chemotherapy, any NSCLC histology, performance status (PS) ECOG 0 or 1, and not scheduled to receive maintenance with pemetrexed or erlotinib. Pts were randomized 2:1 to imetelstat 9.4 mg/kg (d1 and 8 of a 21d cycle) or observation until progressive disease or unacceptable toxicity (concomitant use of bevacizumab was permitted). The 1o endpoint was PFS; safety/tolerability and objective response rate were 2o endpoints. 116 pts were enrolled between Jul 2010 to Apr 2012, with 114 completing a first visit (i.e. efficacy population). Baseline characteristics of age, gender, PS and number of induction cycles were well balanced. 18.4% had squamous histology; 31.6% received concomitant bevacizumab (bev). The median number of imetelstat maintenance cycles was 3. In the overall analysis of PFS, a non significant improvement in favor of the imetelstat arm was observed (HR = 0.77, P=0.295, 95% CI 0.48 - 1.25). Median PFS was 2.8m for imetelstat and 2.6m for control. In the subgroup of patients who did not receive bevacizumab, the HR was 0.59 (vs. 1.07 for the bevacizumab subgroup; interaction P=0.15). The objective response rate was 4.3% in the imetelstat arm and 2.8% in the control arm. Six month overall survival was 80% for imetelstat and 72% for control (HR = 0.86, P=0.642, 95% CI 0.44 - 1.66). Imetelstat was generally well tolerated although hematologic toxicity, predominantly neutropenia and thrombocytopenia, was increased in the imetelstat arm (grade 3/4 neutropenia 18% for imetelstat vs 0% for control, grade 3/4 thrombocytopenia 37% for imetelstat vs 0% for control). The most frequent non-hematologic toxicities were fatigue (imetelstat 42.1% vs control 18.4%), nausea (43.4% vs 7.9%), vomiting (25.0% vs 5.3%) and anaemia (19.7% vs 5.3%). The overall findings suggest that imetelstat has modest, but not clinically meaningful, activity as a maintenance therapy in pts with NSCLC. A pre-specified exploratory subgroup analysis of PFS by tumor telomere length is reported separately. Citation Format: Alberto Chiappori, Tatjana Kolevska, Bart Burington, David Spigel, Steven Hager, Mark Rarick, Shirish Gadgeel, Normand Blais, Joachim Von Pawel, Lowell Hart, Martin Reck, Joan Schiller. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4660. doi:10.1158/1538-7445.AM2013-4660
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".