Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC #704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) Trial - E4599

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

“…The results of a phase III study in patients with advanced NSCLC with adenocarcinoma histology (E4599) showed that the addition of bevacizumab to carboplatin and paclitaxel significantly prolonged survival (62,63). A second planned interim analysis for this study reported a higher response rate (10% versus 27%; P < 0.0001) and improved median progression-free survival (4.5 versus 6.4 months; P < 0.0001) and median overall survival (10.2 versus 12.5 months; P = 0.0075) with the addition of bevacizumab to the treatment regimen (63). To date, this is the first trial in lung cancer to show a survival advantage for a triplet over a doublet regimen first-line (62).…”

“…66). Given that bevacizumab has shown clinical activity in the treatment of first-line breast cancer, colorectal cancer, and NSCLC (53,55,63), it is expected that the clinical activity of bevacizumab will be optimized when used in the first-line treatment of renal cell carcinoma. Several phase II and III trials are ongoing to assess the efficacy of bevacizumab monotherapy or bevacizumab in combination with IFN-a and erlotinib in the first-line setting.…”

“…Bevacizumab does have its own specific safety profile including common and easily manageable adverse events such as hypertension, proteinuria, and mild bleeding and also less common but more serious events such as arterial thromboembolic events, wound healing complications, and serious bleeding events (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). Rare cases of gastrointestinal perforation have been observed (55).…”

A Phase I Dose-Escalation Study of ZD6474 in Japanese Patients with Solid, Malignant Tumors

“…6 Pathological angiogenesis is necessary for the progression of solid, malignant tumors, 7 and inhibition of VEGF-dependent signaling has been identified as a key antiangiogenic strategy. 8,9 The clinical value of inhibiting VEGF signaling in colon cancer, 10 non-small cell lung cancer (NSCLC), 11 and breast cancer 12 has been confirmed with bevacizumab, an anti-VEGF antibody.…”

Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first‐line, systemic chemotherapy

“…7 Some of these agents were evaluated previously in Phase III trials; and, when combined with standard chemotherapy regimens, bevacizumab, an antibody directed against vascular endothelial growth factor (VEGF), produced a survival advantage compared with standard chemotherapy alone. 8 Thus, currently, it is believed widely that the development of these newer agents has had a significant impact on the treatment of advanced NSCLC and that the outcomes of patients enrolled in Phase III trials have improved substantially over the years. However, in the history of systemic chemotherapy for advanced NSCLC, few studies have investigated whether the overall survival of patients with advanced NSCLC enrolled in randomized Phase III trials truly has improved over the years.…”