Nintedanib plus docetaxel shows second-line efficacy in recurrent NSCLC

Feb 19 2014

By Joanna Lyford, Senior medwireNews Reporter

Nintedanib plus docetaxel offers significant efficacy in patients with non-small-cell lung cancer (NSCLC) who experience disease progression after first-line chemotherapy, phase III study results show.

The LUME-Lung 1 trial, reported in The Lancet Oncology, suggests that nintedanib in combination with docetaxel is a valuable second-line option for patients with advanced NSCLC following platinum-based therapy, particularly those with adenocarcinoma.

The trial recruited 1314 patients from 211 centres in 27 countries. All had stage IIIB/IV recurrent NSCLC following first-line chemotherapy. They were randomly assigned to receive docetaxel 75 mg/m² by intravenous infusion on day 1 plus either nintedanib 200 mg orally twice daily (n=655) or matching placebo (n=659) on days 2–21, every 3 weeks.

The study’s primary endpoint was progression-free survival (PFS), assessed after a median of 7.1 months. PFS was 3.4 months, on average, with docetaxel plus nintedanib versus 2.7 months with docetaxel plus placebo, a statistically significant difference with a hazard ratio (HR) of 0.79.

In the subgroup of patients with adenocarcinoma histology, docetaxel plus nintedanib was also associated with a significant improvement in overall survival, measured after 31.7 months of follow-up, at a median of 12.6 months versus 10.3 months with docetaxel plus placebo (HR=0.83).

In this subgroup, the survival curves separated at 6 months and remained separate throughout the 36-month study observation period, note Martin Reck (Lung Clinic Grosshansdorf, Germany) and fellow researchers.

In the total study population, however, the combination of docetaxel plus nintedanib was not superior to docetaxel plus placebo with respect to overall survival (HR=0.94).

The treatment combination had a manageable safety profile, say the study authors. Grade 3 or worse adverse events included diarrhoea (6.6%) and reversible increases in alanine aminotransferase (7.8%) and aspartate aminotransferase (3.4%), all of which were significantly more common with the combination than with docetaxel plus placebo.

Fatal adverse events possibly unrelated to disease progression occurred in 35 (5.4%) of 652 patients taking docetaxel plus nintedanib and 25 (3.8%) of 655 patients taking docetaxel plus placebo. These events included sepsis, pneumonia, respiratory failure and pulmonary embolism.

Reck and co-authors say that future research should include correlative biomarker analyses to try to identify the biological rationale underpinning the response to nintedanib in combination with docetaxel in NSCLC, in particular for patients with adenocarcinoma refractory to first-line therapy.

“The results in these patients might be correlated to the biology of rapidly progressing tumours,” they note.

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