Motesanib flops again in lung cancer

Motesanib has flunked another phase III trial in advanced nonsquamous non–small-cell lung cancer, this time in East Asian patients.

Compared with placebo, the investigational oral vascular endothelial growth factor (VEGF) inhibitor did not significantly improve progression-free survival (PFS) or the secondary endpoint, overall survival (OS), when added to paclitaxel and carboplatin (P/C), reported Kaoru Kubota, MD, of Nippon Medical School, Tokyo, and his associates. “The findings are consistent with overall findings of the phase III MONET1 study but do not replicate those of the subgroup analysis of Asian patients,” they wrote in Journal of Clinical Oncology.

Motesanib is a small-molecular inhibitor of VEGF receptors 1, 2, and 3. In a phase II trial of patients with advanced nonsquamous non–small-cell lung cancer, motesanib resembled the anti-VEGF-A monoclonal antibody bevacizumab in terms of objective response rate, median PFS, and OS when added to paclitaxel and carboplatin. In the subsequent phase III MONET1 trial, however, motesanib plus P/C did not improve PFS over placebo plus P/C, except in a preplanned subgroup analysis of 227 East Asian patients, where it was associated with a 6.4-month greater median PFS (P = .02) and a 1.7-month greater OS (P = .001).

Based on those findings, Dr. Kubota and his associates randomly assigned 401 patients with advanced nonsquamous non–small-cell lung cancer to receive oral motesanib (125 mg) or placebo once daily plus paclitaxel (200 mg/m² IV) and carboplatin (area under the concentration-time curve, 6 mg/mL per min IV) for up to six 3-week cycles. Patients were from Hong Kong, Korea, Japan, and Taiwan; averaged 65 years of age; and 72% were male (J Clin Oncol. 2017 Sep 13. doi: 10.1200/JCO.2017.72.7297).

After a median follow-up of 10 months, median PFS was 6.1 months in the motesanib plus P/C arm and 5.6 months in the placebo plus P/C arm (hazard ratio, 0.81; P = .08). Respective objective response rates were 60% and 42% (P less than .001), median times to tumor response were 1.4 and 1.6 months, and median durations of response were 5.3 and 4.1 months. Motesanib was associated with a higher rate of serious adverse events (87% versus 68%) and a higher rate of treatment discontinuation due to adverse events (33% versus 14%). Motesanib most often caused gastrointestinal disorders, hypertension, cholecystitis, gallbladder enlargement, and liver disorders.

Takeda Pharmaceuticals makes motesanib and sponsored the trial. Dr. Kubota disclosed honoraria and research funding from numerous pharmaceutical companies excluding Takeda. Four coinvestigators disclosed research funding from Takeda and two coinvestigators reported employment with the company. The remaining five researchers had no conflicts.

Motesanib has flunked another phase III trial in advanced nonsquamous non–small-cell lung cancer, this time in East Asian patients.

Compared with placebo, the investigational oral vascular endothelial growth factor (VEGF) inhibitor did not significantly improve progression-free survival (PFS) or the secondary endpoint, overall survival (OS), when added to paclitaxel and carboplatin (P/C), reported Kaoru Kubota, MD, of Nippon Medical School, Tokyo, and his associates. “The findings are consistent with overall findings of the phase III MONET1 study but do not replicate those of the subgroup analysis of Asian patients,” they wrote in Journal of Clinical Oncology.

Motesanib is a small-molecular inhibitor of VEGF receptors 1, 2, and 3. In a phase II trial of patients with advanced nonsquamous non–small-cell lung cancer, motesanib resembled the anti-VEGF-A monoclonal antibody bevacizumab in terms of objective response rate, median PFS, and OS when added to paclitaxel and carboplatin. In the subsequent phase III MONET1 trial, however, motesanib plus P/C did not improve PFS over placebo plus P/C, except in a preplanned subgroup analysis of 227 East Asian patients, where it was associated with a 6.4-month greater median PFS (P = .02) and a 1.7-month greater OS (P = .001).

Based on those findings, Dr. Kubota and his associates randomly assigned 401 patients with advanced nonsquamous non–small-cell lung cancer to receive oral motesanib (125 mg) or placebo once daily plus paclitaxel (200 mg/m² IV) and carboplatin (area under the concentration-time curve, 6 mg/mL per min IV) for up to six 3-week cycles. Patients were from Hong Kong, Korea, Japan, and Taiwan; averaged 65 years of age; and 72% were male (J Clin Oncol. 2017 Sep 13. doi: 10.1200/JCO.2017.72.7297).

After a median follow-up of 10 months, median PFS was 6.1 months in the motesanib plus P/C arm and 5.6 months in the placebo plus P/C arm (hazard ratio, 0.81; P = .08). Respective objective response rates were 60% and 42% (P less than .001), median times to tumor response were 1.4 and 1.6 months, and median durations of response were 5.3 and 4.1 months. Motesanib was associated with a higher rate of serious adverse events (87% versus 68%) and a higher rate of treatment discontinuation due to adverse events (33% versus 14%). Motesanib most often caused gastrointestinal disorders, hypertension, cholecystitis, gallbladder enlargement, and liver disorders.

Takeda Pharmaceuticals makes motesanib and sponsored the trial. Dr. Kubota disclosed honoraria and research funding from numerous pharmaceutical companies excluding Takeda. Four coinvestigators disclosed research funding from Takeda and two coinvestigators reported employment with the company. The remaining five researchers had no conflicts.

Motesanib has flunked another phase III trial in advanced nonsquamous non–small-cell lung cancer, this time in East Asian patients.

Compared with placebo, the investigational oral vascular endothelial growth factor (VEGF) inhibitor did not significantly improve progression-free survival (PFS) or the secondary endpoint, overall survival (OS), when added to paclitaxel and carboplatin (P/C), reported Kaoru Kubota, MD, of Nippon Medical School, Tokyo, and his associates. “The findings are consistent with overall findings of the phase III MONET1 study but do not replicate those of the subgroup analysis of Asian patients,” they wrote in Journal of Clinical Oncology.

Motesanib is a small-molecular inhibitor of VEGF receptors 1, 2, and 3. In a phase II trial of patients with advanced nonsquamous non–small-cell lung cancer, motesanib resembled the anti-VEGF-A monoclonal antibody bevacizumab in terms of objective response rate, median PFS, and OS when added to paclitaxel and carboplatin. In the subsequent phase III MONET1 trial, however, motesanib plus P/C did not improve PFS over placebo plus P/C, except in a preplanned subgroup analysis of 227 East Asian patients, where it was associated with a 6.4-month greater median PFS (P = .02) and a 1.7-month greater OS (P = .001).

Based on those findings, Dr. Kubota and his associates randomly assigned 401 patients with advanced nonsquamous non–small-cell lung cancer to receive oral motesanib (125 mg) or placebo once daily plus paclitaxel (200 mg/m² IV) and carboplatin (area under the concentration-time curve, 6 mg/mL per min IV) for up to six 3-week cycles. Patients were from Hong Kong, Korea, Japan, and Taiwan; averaged 65 years of age; and 72% were male (J Clin Oncol. 2017 Sep 13. doi: 10.1200/JCO.2017.72.7297).

After a median follow-up of 10 months, median PFS was 6.1 months in the motesanib plus P/C arm and 5.6 months in the placebo plus P/C arm (hazard ratio, 0.81; P = .08). Respective objective response rates were 60% and 42% (P less than .001), median times to tumor response were 1.4 and 1.6 months, and median durations of response were 5.3 and 4.1 months. Motesanib was associated with a higher rate of serious adverse events (87% versus 68%) and a higher rate of treatment discontinuation due to adverse events (33% versus 14%). Motesanib most often caused gastrointestinal disorders, hypertension, cholecystitis, gallbladder enlargement, and liver disorders.

Takeda Pharmaceuticals makes motesanib and sponsored the trial. Dr. Kubota disclosed honoraria and research funding from numerous pharmaceutical companies excluding Takeda. Four coinvestigators disclosed research funding from Takeda and two coinvestigators reported employment with the company. The remaining five researchers had no conflicts.