The eagerly awaited first prospective phase III trial in KRAS-mutant non-small-cell lung cancer (NSCLC; N=510), evaluating selumetinib plus docetaxel versus docetaxel alone as second-line treatment (‘SELECT-1’), has failed to meet its primary endpoint of improvement in progression-free survival (PFS).
Dr Pasi Jänne from Dana-Farber Cancer Institute, Boston, Massachusetts, USA, presented the findings in a Late-Breaking Abstract presentation yesterday (Abstract LBA47_PR). He noted that despite observing a significant improvement in PFS and response with the MEK1/2 inhibitor combination in an earlier phase II study,1 the phase III data were disappointing in this KRAS-mutant population that is associated with a particularly poor prognosis and is notoriously difficult to treat. Median PFS was 3.9 months with selumetinib plus docetaxel and 2.8 months with placebo plus docetaxel (hazard ratio 0.93; 95% confidence interval 0.77–1.12; p=0.44). Similarly, the combination did not show a significant effect on overall survival, while a trend towards a higher objective response rate was observed with selumetinib compared with placebo (20.1% versus 13.7%; odds ratio 1.61; p=0.051). The selumetinib plus docetaxel combination was associated with a higher incidence of grade ≥3 adverse events (AEs), serious AEs, and AEs leading to hospitalisation compared with the docetaxel arm.
Selumetinib was granted Orphan Drug Designation by the US FDA in May 2016 for the adjuvant treatment of thyroid cancer and is being further investigated as an adjuvant treatment option for high-risk thyroid cancer (for its capacity to re-sensitise tumour cells to radioactive iodine) and other tumour types.
- Jänne PA, et al. Lancet Oncol 2013;14:38–47
This article appeared in the Tuesday edition of the Daily Reporter