The combination of nintedanib and docetaxel “is an effective second-line option” for patients with advanced non–small cell lung cancer (NSCLC) who have received previous treatment with one line of platinum-based therapy, according to results from the phase III LUME-Lung 1 study published in The Lancet Oncology. The combination improved progression-free survival for patients with refractory NSCLC irrespective of histology when compared to docetaxel (Taxotere) plus placebo, and “significantly prolonged overall survival of patients with adenocarcinoma, including patients with poor prognosis (ie, those who had progressed within 9 months of start of first-line therapy),” Martin Reck, MD, Lung Clinic Grosshansdorf, Germany, and colleagues reported for the LUME-Lung 1 Study Group.
Nintedanib (formerly BIBF 1120) is an oral angiokinase inhibitor previously shown to have antitumor activity in patients with solid tumors (including NSCLC), a manageable safety profile, and limited drug-drug interactions. The phase III trial involved patients from 211 centers in 27 countries. The median age was 60 years, and all patients had stage IIIB/IV recurrent NSCLC that had progressed after first-line chemotherapy.
Patients were randomly assigned to receive docetaxel with nintedanib (655 patients) or with placebo (659 patients). “Patients were assigned to docetaxel 75 mg/m² by intravenous infusion on day 1 plus nintedanib 200 mg twice daily orally or matching placebo on days 2 to 21, every 3 weeks. Treatment was continued until unacceptable adverse events or disease progression,” the investigators explained. “The study was jointly designed by academic investigators and representatives of the sponsor, Boehringer Ingelheim,” the authors noted.
As determined by central independent review, progression-free survival was significantly longer in the docetaxel-plus-nintedanib group than in the docetaxel-plus-placebo group (median, 3.4 months [95% confidence interval (CI) = 2.9–3.9] vs 2.7 months [2.6–2.8], hazard ratio [HR] = 0.79 [95% CI = 0.68–0.92], P = .0019), the investigators reported. “Similar results were noted both in patients with adenocarcinoma and patients with squamous-cell carcinoma.”
For all patients combined, there was no difference in overall survival between the two treatment groups, but for patients with adenocarcinoma, overall survival was significantly longer in the docetaxel/nintedanib group than in the docetaxel/placebo group (median, 12.6 months [95% CI = 10.6–15.1] vs 10.3 months [95% CI = 8.6–12.2], HR = 0.83 [95% CI = 0.70–0.99], P =.0359).
“The combination of nintedanib and docetaxel seems to be especially beneficial in adenocarcinoma patients with poor prognosis, for whom there is a high unmet need, such as patients with progressive disease in the first-line setting,” or those who have progression within 9 months after the initiation of first-line therapy, the authors commented. Among those patients, overall survival was significantly longer in the docetaxel/nintedanib group than in the docetaxel/placebo group (median, 10.9 months [95% CI = 8.5–12.6] vs 7.9 months [6.7–9.1], HR = 0.75 [95% CI = 0.60–0.92], P = .007.
Several adverse events were more common in the docetaxel/nintedanib group than in the docetaxel/placebo group. These include diarrhea, which occurred in 42.3% of the combination group vs 21.8% of the placebo group; nausea, 24.2% vs 18.0%; decreased appetite, 22.2% vs 15.6%; and vomiting, 16.9% vs 9.3%. “Most of these adverse events were manageable with supportive treatment or dose reduction,” the authors wrote.
Adverse events leading to death related to disease progression occurred in 72 (11.0%) of 652 patients in the docetaxel plus nintedanib group and in 52 (7.9%) of 655 patients in the docetaxel plus placebo group. Adverse events leading to death possibly unrelated to disease progression were reported in 35 patients (5.4%) in the docetaxel/nintedanib group and in 25 patients (3.8%) in the docetaxel/placebo group.
The authors noted that to the best of their knowledge, none of the antiangiogenic compounds tested in the first- or second-line setting have shown any effect on overall survival in advanced NSCLC. “Up to now, bevacizumab [Avastin] was the only antiangiogenic drug shown to prolong overall survival in advanced NSCLC when combined with chemotherapy (paclitaxel or carboplatin) in the first-line setting,” they wrote. ■