Abstract 2376: Improved progression-free survival (PFS) in patients with short tumor telomere length: Subgroup analysis from a randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced NSCLC .
Bibliographic record
Abstract
Abstract Tumor regrowth after chemotherapy may be driven by growth of tumor ‘stem cells’. Telomerase, required for indefinite replication, is upregulated both in putative ‘stem cells’ and bulk tumor cells. Imetelstat, a lipidated 13-mer oligonucleotide, is a potent and specific inhibitor of telomerase. A randomized phase II study was conducted to assess whether imetelstat, given as maintenance therapy, prolongs PFS in advanced NSCLC: results for the primary and secondary endpoints are reported separately. NSCLC cell lines and other tumor cells with short telomeres appear to be more sensitive to imetelstat in vitro than those with long telomeres. A planned exploratory analysis to determine PFS as a function of tumor telomere length (TL) was performed. Tumor TL was assessed in archival tumor specimens from pts by quantitative PCR (qPCR). TL data were available for 57 of the 116 pts accrued in the clinical trial. PFS was evaluated in patients grouped into the shortest 1/2, shortest 1/3 and shortest 1/4 of TL. In 19 pts with the shortest 1/3 TL measured by qPCR, imetelstat maintenance increased PFS with a HR in favor of the imetelstat arm of 0.32 (95% CI 0.1 to 1.0), p=0.042 (un-stratified log rank). Median PFS was 4.0 months for the imetelstat-treated short TL sub-group and 1.5 months for the control short TL sub-group. In the 38 pts with the longest 2/3 TL HR was 0.83 (95% CI 0.36 to 1.9). Results in the group with the shortest 1/4 of TL were similar to the shortest 1/3 TL group, and in the shortest 1/2 group, results were consistent but attenuated, indicating that a smaller subset may contain patients with the most potential to benefit. In the control arm, short TL was associated with shorter median PFS (1.48 months) compared to patients with long TL (2.7 months), suggesting that short TL has a negative prognostic value. These findings suggest that imetelstat given as maintenance therapy prolongs PFS in pts with advanced NSCLC whose tumors have short telomeres as measured by qPCR. The data are consistent with the hypothesis that clinical benefit from telomerase inhibition is greater in patients with tumors possessing short telomeres. Prospective confirmation of these results in solid tumors and hematologic neoplasms is planned. Citation Format: Alberto Chiappori, Ekaterina Bassett, Bart Burington, Tatjana Kolevska, David R. Spigel, Steven Hager, Mark Rarick, Shirish Gadgeel, Normand Blais, Joachim Von Pawel, Lowell Hart, Hui Wang, Kevin Eng, Martin Reck, Joan Schiller. Improved progression-free survival (PFS) in patients with short tumor telomere length: Subgroup analysis from a randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced NSCLC . [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 2376. doi:10.1158/1538-7445.AM2013-2376
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.004 | 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 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".