Tolerability of Eribulin and Correlation Between Polymorphisms and Neuropathy in an Unselected Population of Female Patients with Metastatic Breast Cancer: Results of The Multicenter, Single Arm, Phase IV PAINTER Study
Bibliographic record
Abstract
Abstract BACKGROUNDMetastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients (pts) overall survival (OS) and improving their quality of life. eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. Its common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN).METHODSThe PAINTER is a single arm, phase IV study, aimed at surveying eribulin tolerability in MBC pts. Secondary objectives were to explore incidence and severity of PN, its association with genetic polymorphisms, and the description of treatment efficacy and safety. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The associations between PN and SNPs were evaluated by Fisher exact test.RESULTSFrom May 2014 to June 2018 180 pts were enrolled from 20 Italian centers; 170 were evaluable for efficacy and toxicity and 159 for polymorphisms analysis. Median age was 60 years, biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. With a median follow up of 15.4 months, a median number of eribulin cycles of 4.5 (minimum-maximum 1-23), median overall survival was 12 months. 48.8% of pts experienced dose reduction, mainly for neutropenia (23.9%) and liver injury (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7% respectively); other toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver injury (6.6%), pulmonary toxicity (6.5%) and dermatological (3.6%), Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723. CONCLUSIONSEribulin is a well-tolerated treatment in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in NDRG1 gene and rs7214723 (CC and CT) in CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored eribulin treatment in cancer patients.Trial registration: ClinicalTrials.gov ID: NCT02864030EudraCT: 2013-004600-19
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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 | 0.001 | 0.001 |
| 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 | 0.000 | 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 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".