NSCLC... could be an opportunity. could be a complication.
Combined targeted therapy led to almost a 50% increase in PFS in patients with previously untreated advanced NSCLC who had activating EGFR mutations, a randomized trial showed.
First-line treatment with the combination of erlotinib (Tarceva) and bevacizumab (Avastin) was associated with a median PFS of 16.0 months compared with 9.7 months with erlotinib alone. The combination had a moderately higher rate of grade =3 adverse events, as reported in The Lancet Oncology.
"Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC," Nobuyuki Yamamoto, MD, PhD, of Wakayama Medical University in Wakayama, Japan, and co-authors concluded. "Further investigation of the regimen is warranted."
A substantial proportion of patients with NSCLC have tumors with EGFR mutations. For those patients, treatment with an EGFR inhibitor, such as erlotinib, has been standard. Despite improved PFS with EGFR inhibitors, most patients' tumors eventually develop resistance to the agents, leading to relapse within 1 year in most cases, the authors noted.
Bevacizumab is an angiogenesis inhibitor that targets the VEGF signaling pathway and has been shown to improve outcomes in nonsquamous NSCLC when added to first-line platinum-based chemotherapy. Some lung cancer authorities have speculated that simultaneous targeting of EGFR and VEGF might lead to further improvement in PFS, the authors continued.
To evaluate first-line treatment with the two targeted agents, Yamamoto and colleagues performed a phase II multicenter randomized trial involving 154 patients with previously untreated advanced (stage IIIB/IV) nonsquamous NSCLC. Patients received either erlotinib alone or in combination with bevacizumab. In all cases, tumor specimens were screened to confirm the presence of EGFR activating mutations.
The primary endpoint was PFS, and secondary endpoint included OS, tumor response, disease control, and duration of response. Patient accrual was based on the assumption of a median PFS of 13 months for patients treated with erlotinib alone.
Analysis of the primary endpoint demonstrated a significant advantage in PFS for patients treated with the combination (P=0.0015). Subgroup analysis did not identify patients who appeared to benefit more or less with the combination, the authors reported.
Patients whose tumors had exon 19 deletions (half of each group) had better PFS. The combination arm had a median PFS of 18.0 months versus 10.3 months with erlotinib alone (HR 0.41, P=0.0011).
