Abstract LB-75: Concomitant use of panitumumab (Pmab) had no clinically significant effect on irinotecan (Iri) pharmacokinetics (PK)
Bibliographic record
Abstract
Abstract Background: Pmab, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFR), is indicated for treatment of EGFR-expressing, chemorefractory, metastatic colorectal cancer (mCRC). This study examined effects of Pmab on Iri PK when used as combination therapy in patients (pts) with mCRC. Methods: This phase 1, open-label, multicenter, single-arm study enrolled pts with mCRC without prior exposure to an EGFR inhibitor. Pts could not have CYP3A4 inhibiting or inducing medications ≥ 2 weeks before enrollment or UGT1A1*28 TA7/7, TA7/8, and TA8/8 polymorphisms. Pts received Iri (180 mg/m2, 90-min IV infusion) on day 1 cycle 1 followed by Pmab (6 mg/kg, 60-min IV infusion) on day 4 cycle 1. After 2 weeks (day 1 cycle 2), pts received Pmab followed immediately by Iri. Pmab and Iri were administered thereafter every 2 weeks until disease progression or intolerability. Plasma samples for Iri and its active metabolite SN-38 were collected pre-dose and up to 72 hours after Iri infusion in cycles 1 and 2. Primary endpoints were Cmax and AUC of Iri (PK subset), and secondary endpoints included rates of adverse events (AEs). Results: 28 pts enrolled; 19 of 27 pts who received treatment met PK evaluability criteria (dosed per protocol for 2 cycles with no reductions/delays). PK profiles of Iri with or without Pmab were nearly superimposable. 90% confidence intervals for the ratios of geometric means for Iri Cmax and AUC with or without Pmab were within a prespecified 0.70 to 1.43 interval, suggesting that Pmab had no impact on Iri PK. Similar results were seen for SN-38 PK. AEs were as expected for Iri plus Pmab combination therapy. Conclusions: Pmab in combination with Iri was generally well tolerated by pts with mCRC. Pmab had no significant effects on Iri PK.PK Profiles of Iri and SN-38 Ratio of Geometric Means Point Estimate Cycle (N = 19)Geometric Mean(Cycle 2 vs Cycle 1)90% CIIri Cmax (ng/mL)115400.9800.894 - 1.074 21510 AUC0-inf (ng·hr/mL)1112000.8980.819-0.985 210100 SN-38 Cmax (ng/mL)125.90.8230.731-0.926 221.3 AUC0-inf (ng·hr/mL)1a3260.8650.773 - 0.968 2b282 aN = 17; bN = 16; CI, Confidence interval; Iri, Irinotecan Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-75.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".