“Thus, in common with every other superiority trial undertaken to compare a novel agent or regimen to standard therapy in second-line NSCLC, improvement of OS has proven to be an elusive goal,” the researchers conclude in their report in the Journal of Clinical Oncology online September 10.
Dr. Rodryg Ramlau, at Poznan University of Medical Sciences in Poland, and colleagues point out that despite advances in first-line therapy, most NSCLC patients experience progression and may benefit from second-line treatment with agents that include docetaxel, pemetrexed, gefitinib, or erlotinib. Still, overall survival remains about 7 to 9 months.
Aflibercept (ziv-aflibercept in the US) is a recombinant human fusion protein that blocks the VEGF pathway by binding to the VEGF-A and –B isoforms, and it has shown good tolerability in combination with docetaxel in a phase I trial involving heavily pretreated patients with solid tumors, according to the report.
In the current trial, the team compared the efficacy of docetaxel plus aflibercept to docetaxel alone in a randomized phase III trial involving 913 platinum-pretreated patients with advanced or metastatic nonsquamous NSCLC.
Median overall survival, the primary outcome, was 10.1 months in the aflibercept arm compared with 10.4 months in the docetaxel-only arm (hazard ratio 1.01; p=0.90), the investigators report.
They did find an indication of benefit with aflibercept treatment compared to docetaxel alone in terms of progression free survival (5.2 vs 4.1 months; hazard ratio 0.82; p=0.0035) and overall response rate (23.3% vs 8.9%; p<0.001).
However, adverse events of grade 3 or higher occurred more often in the aflibercept arm. For example, rates of neutropenia were 28.0% with aflibercept compared to 21.1% without, and respective rates of stomatitis were 8.8% versus 0.7%)
In fact, “The addition of (ziv-)aflibercept led to 3% more progression-unrelated fatalities,” Dr. Ramlau and colleagues report.
“In conclusion,” they write, “the addition of (ziv-)aflibercept to standard docetaxel therapy did not improve OS of pretreated patients with NSCLC.”