Phase 2 study of single agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer Full Text
Clinical Cancer Research,
Rudin CM et al. – Bcl-2 targeting by navitoclax demonstrates limited single agent activity against advanced and recurrent SCLC. Correlative analyses suggest several putative biomarkers of clinical benefit. Preclinical models support that navitoclax may enhance sensitivity of SCLC and other solid tumors to standard cytotoxics.Methods
- 39 patients received navitoclax 325mg daily, following an initial lead-in of 150mg daily x 7 days.
- Study endpoints included safety and toxicity assessment, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates.
- The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade 3-4 in 41% of patients.
- Partial response was observed in one (2.6%) patient and stable disease in 9 (23%).
- Median PFS was 1.5 months, and median OS 3.2 months.
- A strong association between plasma pro-gastrin releasing peptide (pro-GRP) level and tumor Bcl-2 copy number (R=0.93) was confirmed.
- Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, pro-GRP, and circulating tumor cell number as correlates of clinical benefit.