AI Article Synopsis
- ABT-751, an antimitotic agent, was tested alongside pemetrexed in a study involving 171 patients with advanced non-small-cell lung cancer (NSCLC) to evaluate its effectiveness and safety.
- Patients received either ABT-751 or a placebo over 21-day cycles, with the primary goal of measuring progression-free survival (PFS) and secondary outcomes including overall survival (OS) and pharmacokinetics.
- While overall results showed no significant improvement in PFS for the entire group, a notable benefit in OS was found in the squamous NSCLC subgroup, highlighting ABT-751’s potential in this specific patient population along with identified biomarkers that may predict survival outcomes.
Article Abstract
Purpose: ABT-751 is an antimitotic and vascular disrupting agent with potent preclinical anticancer activity. We conducted a phase I and randomized double-blind phase II study of pemetrexed with ABT-751 or placebo in patients with recurrent advanced or metastatic non-small-cell lung cancer (NSCLC).
Methods: One hundred seventy-one patients received intravenous pemetrexed 500 mg/m(2) day 1 and oral ABT-751 or placebo days 1 to 14 of 21-day cycles. The primary end point was progression-free survival (PFS). Secondary end point included overall survival (OS); pharmacokinetic and pharmacodynamic parameters were also analyzed.
Results: The recommended phase II dose of ABT-751 with pemetrexed is 200 mg. Fatigue, constipation, anemia, nausea, and diarrhea were the most common toxicities in both study arms. No pharmacokinetic interactions were observed. Median PFS in the ABT-751 arm was 2.3 months versus 1.9 for placebo (P = .819, log-rank) for the intention-to-treat population. However, differences in PFS (P = .112, log-rank) and OS (P = .034, log-rank; median 3.3 v 8.1 months) favoring ABT-751 were seen in the squamous NSCLC subgroup. Baseline circulating tumor cell concentrations were predictive of improved OS (P = .013). Changes from baseline of greater than 20% in plasma levels of placenta growth factor (P = .056), squamous cell carcinoma antigen (P = .03), and cytokeratin 19 fragment antigen 21-1 (P = .01) were markers best associated with improved OS.
Conclusion: Addition of ABT-751 to pemetrexed is well-tolerated, but does not improve outcome in unselected patients with recurrent NSCLC. ABT-751 may have therapeutic potential in squamous NSCLC. Exploratory cellular and molecular analyses in this study identified biomarkers that may correlate with survival.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672026 | PMC |
| http://dx.doi.org/10.1200/JCO.2010.32.5944 | DOI Listing |
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