Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer

Abstract

Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH-negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.

Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

“…However, subset analyses by Spigel et al in the trail showed a benefit in EGFR WT and EGFR FISH-negative patients for the combination of erlotinib/ sorafenib compared with single-agent erlotinib with respect to PFS and OS (Spigel et al, 2011). Similarly, a multicenter phase II study of erlotinib and sorafenib in chemotherapy-naive patients with advanced non-small cell lung cancer also suggested that patients with wildtype EGFR had a higher ORR than previously reported for single-agent erlotinib/sorafenib (Lind et al, 2010).…”

“…In previouslytreated NSCLC patients, sorafenib also failed to show additional benefits in combination with pemetrexed in a phase II trial (Molina et al, 2011). In a randomized, double-blind, placebo-controlled Phase II trial of sorafenib and erlotinib or erlotinib alone, sorafenib did not statistically improve DCR , PFS and OS when combined with erlotinib in patients with relapsed NSCLC (Spigel et al, 2011). Nevertheless, another Phase III clinical trial NExUS still showed a clinically modest but statistically significant prolongation in progression-free survival for the sorafenib plus cisplatin/gemcitabine arm compared to cisplatin/ gemcitabine alone (6.1 versus 5.5 months, p<0.001) (PazAres LG et al, 2012).…”

“…There were 1409 and 1339 patients randomized to SBT and to the control arms, respectively. Of the included studies, two studies compared sorafenib alone vs. placebo (Paz-Ares L et al, 2012;Wakelee et al, 2012), one study compared sorafenib plus EGFR-TKIS vs. EGFR-TKIS (Spigel et al, 2011), three studies compared sorafenib plus chemotherapy vs. chemotherapy (Scagliotti et al, 2010;Molina et al, 2011;Paz-Ares LG, et al, 2012). The process of study selection is shown in a flow chart (Figure 1).…”

“…It has been approved for advanced renal cell carcinoma and hepatocellular carcinoma (Escudier et al, 2007;Llovet et al, 2008 ). Many clinical trials have been conducted to evaluate sorafenib in the treatment of advanced NSCLC, either as a single agent, in combination with chemotherapy or targeted agents, but the results on the efficacy of such trials are inconsistent (Scagliotti et al, 2010;Molina et al, 2011;Spigel et al, 2011;Paz-Ares L et al, 2012;Wakelee et al, 2012). Therefore, we have undertaken this meta-analysis to evaluate the available evidence from the relevant RCTs.…”

Anti-angiogenetic therapies for central nervous system metastases from non-small cell lung cancer

“…Drug-related bleeding was observed in four patients and hemorrhagic/bleeding and neurological events were more common in patients with SCC (37.5% and 75%, respectively) compared to other histology. A phase II trial evaluated the efficacy of sorafenib plus erlotinib vs. placebo plus erlotinib in patients with advanced NSCLC, pretreated with one or two regimens (63 …”