Nintedanib and docetaxel provide small PFS advantage in NSCLC

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.

PFS was significantly better both in patients with adenocarcinoma histologies treated with the combination (median 4.0 vs. 2.8 months; HR, 0.77; P = .0193) and with squamous cell carcinomas (2.9 vs. 2.6 months; HR, 0.77; P = .02).

Overall survival did not differ, at a median of 10.1 vs. 9.1 month. Among patients with adenocarcinomas, however, survival was significantly better, at a median of 12.6 vs. 10.3 months, respectively (HR, 0.82; P = .0359). There was also a hint of benefit in patients with adenocarcinomas refractory to prior chemotherapy with a platinum compound (median overall survival, 9.8 vs. 6.3 months; HR, 0.62; P = .0246), although this subanalysis included only 107 patients.

The combination was no better than docetaxel and placebo among patients with squamous cell cancers.

Grade 3 or greater adverse events occurred in 71% of patients on nintedanib/docetaxel, and 64% of controls. In each group, about 22% of patients had adverse events leading to discontinuation of therapy. The most common adverse events were bleeding, thromboembolic events, and hypertension, each of which occurred more frequently with the combination than with docetaxel alone.

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.

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.

PFS was significantly better both in patients with adenocarcinoma histologies treated with the combination (median 4.0 vs. 2.8 months; HR, 0.77; P = .0193) and with squamous cell carcinomas (2.9 vs. 2.6 months; HR, 0.77; P = .02).

Overall survival did not differ, at a median of 10.1 vs. 9.1 month. Among patients with adenocarcinomas, however, survival was significantly better, at a median of 12.6 vs. 10.3 months, respectively (HR, 0.82; P = .0359). There was also a hint of benefit in patients with adenocarcinomas refractory to prior chemotherapy with a platinum compound (median overall survival, 9.8 vs. 6.3 months; HR, 0.62; P = .0246), although this subanalysis included only 107 patients.

The combination was no better than docetaxel and placebo among patients with squamous cell cancers.

Grade 3 or greater adverse events occurred in 71% of patients on nintedanib/docetaxel, and 64% of controls. In each group, about 22% of patients had adverse events leading to discontinuation of therapy. The most common adverse events were bleeding, thromboembolic events, and hypertension, each of which occurred more frequently with the combination than with docetaxel alone.

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.

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.

PFS was significantly better both in patients with adenocarcinoma histologies treated with the combination (median 4.0 vs. 2.8 months; HR, 0.77; P = .0193) and with squamous cell carcinomas (2.9 vs. 2.6 months; HR, 0.77; P = .02).

Overall survival did not differ, at a median of 10.1 vs. 9.1 month. Among patients with adenocarcinomas, however, survival was significantly better, at a median of 12.6 vs. 10.3 months, respectively (HR, 0.82; P = .0359). There was also a hint of benefit in patients with adenocarcinomas refractory to prior chemotherapy with a platinum compound (median overall survival, 9.8 vs. 6.3 months; HR, 0.62; P = .0246), although this subanalysis included only 107 patients.

The combination was no better than docetaxel and placebo among patients with squamous cell cancers.

Grade 3 or greater adverse events occurred in 71% of patients on nintedanib/docetaxel, and 64% of controls. In each group, about 22% of patients had adverse events leading to discontinuation of therapy. The most common adverse events were bleeding, thromboembolic events, and hypertension, each of which occurred more frequently with the combination than with docetaxel alone.

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.