The number of new cases of cancer is estimated to be 1,638,910 in 2012.1 Lung cancer is the second most common cancer, accounting for 14% of new cases. Importantly, lung cancer has the highest occurrence of cancer related death; it accounts for 29% of males and 26% of females whose cause of death is cancer.1 The mortality rate associated with lung cancer remains high even though there have been improvements in treatment. Innovations in the prevention and treatment of lung cancer have accounted for the decline in lung cancer related mortality by as much as 2.6% per year in men and 0.9% per year in women.1 The World Health Organization (WHO) divides lung cancer into two major categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC); NSCLC being the more prevalent type. NSCLC can be subdivided into squamous and non-squamous; non-squamous contains but is not limited to adenocarcinoma, large-cell carcinoma, and adenocarcinoma in situ.
Treatment of advanced, non-squamous NSCLC has become increasingly individualized based on tumor histology and genetic mutations. One of the first line treatments of advanced disease, ignoring genetic mutations, is chemotherapy with a platinum medication, such as carboplatin or cisplatin. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is added to the above regimen as long as the patient does not have squamous cell histology.2 The patient may be tested further to help determine if treatment for mutations in either epidermal growth factor receptor (EGFR) or anaplastic lymphoma receptor (ALK) is beneficial.
The MONET1 trial was undertaken because of the promising results of bevacizumab in the AVAiL and ECOG4599 trials. The ECOG4599 study compared the use of bevacizumab versus placebo in combination with carboplatin and paclitxel in advanced NSCLC. Bevacizumab showed an increase in overall survival (OS) of 12.3 months versus 10.3 months in placebo group (p=0.003), and increased progression free (PFS) survival of 6.2 months versus 4.5 months in placebo (p<0.001).3 In the AVAiL study, bevacizumab was compared to placebo in combination with cisplatin and gemcitabine, though only a significance in PFS (p=0.023) was found, not OS as in the E4599 study.4 Prior studies using bevacizumab showed an increased risk of hemoptysis and early mortality in patients with squamous cell tumors, thus use in this population is avoided.5
Bevacizumab’s mechanism of action is similar to motesanib as they are both inhibitors of the VEGF receptors, though motesanib also inhibits platelet-derived growth factor receptor (PDGFR), and c-kit receptor tyrosine kinase (KIT)5. The MONET1 trial (N=1,090), an international, randomized, placebo-controlled, double blind, phase III study, tested motesanib versus placebo in combination with carboplatin and paclitaxel in patients with advanced nonsquamous NSCLC.5 Patients received either motesanib 125mg once daily or placebo for an average of 4.1 months along with the regimen of paclitaxel 200 mg/m2 and carboplatin AUC 6 mg/ml/min every 21 days. The primary end point of the study was OS with secondary endpoints being PFS, ...