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Nintedanib and docetaxel provide small PFS advantage in NSCLC


AT THE ASCO ANNUAL MEETING 2013


Vitals

Major finding: Median progression-free survival was 3.4 months for patients randomized to nintedanib and docetaxel, compared with 2.7 months for patients assigned to placebo and docetaxel (P = .019)

Data source: Randomized, placebo controlled trial in 1,314 patients, 1,134 of whom were included in the primary endpoint analysis.

Disclosures: The LUME-Lung 1 trial was sponsored by Boehringer Ingelheim. Dr. Reck disclosed serving as an advisor and lecturer for Hoffman-La Roche, Lilly, AstraZeneca, Pfizer, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Besse reported serving as an uncompensated advisor to Boehringer Ingelheim.

CHICAGO – A combination of docetaxel and nintedanib, a novel inhibitor of multiple tumor growth factors, was associated with a small but significant improvement in progression-free survival in patients with advanced non–small cell lung cancer as compared with docetaxel alone.

In the phase III LUME-Lung I trial in patients with previously treated stage IIIB/IV or recurrent non–-small cell lung cancer (NSCLC), median progression-free survival (PFS) was 3.4 months for patients randomized to nintedanib and docetaxel, compared with 2.7 months for patients assigned to placebo and docetaxel (hazard ratio, 0.79; P = .0019), reported Dr. Martin Reck of the department of thoracic oncology at Hospital Grosshansdorf, Germany.

In addition, "we have seen a significant improvement of overall survival in patients with adenocarcinoma," Dr. Reck said at the annual meeting of the American Society of Clinical Oncology.

However, when patients with squamous cell NSCLC were included in the analysis, there was no significant difference in overall survival between the treatment groups, he said.

Nintedanib is an oral kinase inhibitor that targets vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-3, platelet-derived growth factor receptors alpha and beta, and the RET tyrosine kinase.

In clinical trials, nintedanib has been delivered safely in combination with various chemotherapy agents, including docetaxel, paclitaxel, platinum comp2ounds, and gemcitabine, and as a single agent had clinical activity in a phase II trial against recurrent NSCLC.

Dr. Reck and his colleagues enrolled 1,314 patients with stage IIIB or IV or recurrent NSCLC after first-line chemotherapy and randomly assigned them in a double-blinded fashion to receive intravenous docetaxel 75 mg/m2 on day 1 of a 21-day cycle plus either oral nintedanib 200 mg or placebo twice daily on days 2 through 21 of each cycle. The number of potential docetaxel cycles was unlimited, and docetaxel monotherapy could continue after four cycles of the combination at the investigator’s discretion.

Patients were stratified by performance status, prior bevacizumab (Avastin) use, squamous or nonsquamous histology, and presence or absence of brain metastases.

As of the February 2013 data cutoff, 6 of the 652 patients assigned to the combination and 6 of the 655 assigned to docetaxel/placebo remained on study.

In the intention-to-treat analysis, the trial met its primary endpoint of a centrally reviewed PFS advantage for the combination.

Continued...

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Data lacking for 14% of study group

The progression-free survival analysis was performed in 1,134 (86%) of the 1,314 patients randomized, because the PFS data cutoff occurred 3 months before the actual completion of trial accrual. Also, there was a 2-year gap between the final PFS analysis and the overall survival analysis.

Although the study was reported as being positive, the lack of PFS data on 14% of the population precluded a full intention-to-treat analysis. It would be interesting to see whether the survival benefit with nintedanib in patients with adenocarcinomas would remain if this subgroup of patients were further stratified by prior bevacizumab exposure. Further, the apparent advantage for the combination in patients with platinum-refractory adenocarcinomas needs to be validated in larger studies.

Dr. Benjamin Besse is a thoracic oncologist at the Institut Gustave-Roussy in Villejuif, France. Dr. Besse, who was the invited discussant of the study, reported serving as an uncompensated advisor to Boehringer-Ingelheim.

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