Nintedanib Plus Docetaxel Improves PFS and OS for Patients with Stage IIIB/IV or Recurrent Lung Adenocarcinoma

Maria Vinall

doi:10.1177/155989771306008

Summary

Nintedanib plus docetaxel significantly improved progression-free survival independent of histology, and prolonged overall survival for non-small cell lung cancer (NSCLC) with adenocarcinoma histology. Adverse events were generally manageable with dose reductions and symptomatic treatment. This article reports on results from the BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in Second-Line Non-Small Cell Lung Cancer study [LUME-Lung 1; NCT00805194; Reck M et al. J Clin Oncol 2013 (suppl; abstr LBA8011)], a placebo-controlled Phase 3 trial of nintedanib plus docetaxel in patients with locally advanced/metastatic NSCLC progressing after first-line therapy.

Oncology Clinical Trials
Cancer
Respiratory Cancers

Oncology Clinical Trials
Cancer
Oncology
Respiratory Cancers

Nintedanib plus docetaxel significantly improved progression-free survival (PFS) independent of histology, and prolonged overall survival (OS) for non-small cell lung cancer (NSCLC) with adenocarcinoma histology. Adverse events (AEs) were generally manageable with dose reductions and symptomatic treatment.

No targeted agent has been shown to prolong OS in combination with second-line chemotherapy in NSCLC. Inhibition of tumor-related angiogenesis has been identified as an attractive target for antitumor therapy. Nintedanib is an oral angiokinase inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and fibroblast growth factors. Martin Reck, MD, PhD, Hospital Grosshandorf, Grosshansdorf, Germany, reported results from the BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in Second-Line Non-Small Cell Lung Cancer study [LUME-Lung 1; NCT00805194; Reck M et al. J Clin Oncol 2013 (suppl; abstr LBA8011)], a placebo-controlled Phase 3 trial of nintedanib plus docetaxel in patients with locally advanced/metastatic NSCLC progressing after first-line therapy.

Patients with histologically or cytologically confirmed locally advanced (stage IIIB), metastatic stage IV or recurrent NSCLC in whom first-line chemotherapy failed, were randomized to oral nintedanib 200 mg BID on Days 2 to 21 plus intravenous docetaxel 75 mg/m² Q21D (n=655) or placebo plus docetaxel (n=659). The number of docetaxel cycles was not restricted. Monotherapy was permitted after ≥4 cycles of combination therapy.

The primary study endpoint was PFS assessed by independent central review using RECIST v1.0. Imaging was performed every 6 weeks. The key secondary endpoint of OS was analyzed hierarchically first in adenocarcinoma patients <9 months since start of first-line therapy (T <9 months; identified as a prognostic/predictive biomarker), followed by all adenocarcinoma patients, and then all patients. Additional secondary analyses included response rate, safety, and patient reported outcomes.

The study participants were mostly men (73%), with a mean age of ∼68 years; ∼75% of participants were current or past smokers. Approximately 50% of patients had adenocarcinoma histology and 42% had squamous cell carcinoma. At randomization ∼90% of patients had metastatic disease and >90% had received platinum-based chemotherapy as first-line treatment.

Nintedanib plus docetaxel significantly prolonged PFS versus placebo plus docetaxel (HR, 0.79; 95% CI, 0.68 to 0.92; p=0.0019; median 3.4 vs 2.7 months) regardless of histology (squamous HR, 0.77; p=0.0200; adenocarcinoma HR, 0.77; p=0.0193). The results were also consistent among all previously specified subgroups.

There was no difference in OS in the intention-to-treat population of all patients. OS was significantly prolonged in patients with adenocarcinoma histology (HR, 0.83; p=0.0359; median 12.6 vs 10.3 months) but not those with squamous cell carcinoma. Tumor response was comparable between both arms and between the major histologies; however, there was a significant increase in disease control rates (complete response+partial response+stable disease) with nintedanib plus docetaxel in patients with adenocarcinoma (OR, 1.93; p<0.0001) and squamous cell carcinoma (OR, 1.78; p<0.0009).

There was a higher incidence of drug-related adverse events (AEs) and severe drug-related AEs in the combination-therapy group. However, there was no difference in the number of AEs leading to drug discontinuation or the incidence of serious AEs. The most common AEs associated with combination therapy were gastrointestinal (diarrhea 42.3% vs 21.8%, and nausea) and transient elevation of transaminases (28.5% vs 8.4%). The side effects were mostly low to moderate in intensity, and nearly all were reversible. Further investigations are warranted to identify molecular and clinical determinants of benefit for nintedanib in NSCLC.

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