Pemetrexed, oxaliplatin and bevacizumab as first-line treatment in patients with stage IV non-small cell lung cancer.

BACKGROUND: Oxaliplatin has less haematological toxicity than cisplatin and carboplatin. The combination of pemetrexed, oxaliplatin and bevacizumab appeared well tolerated and active as second- or third-line treatment in a previous phase II study. Its role as first-line therapy remains to define. PATIENTS AND METHODS: From August 2008 to May 2011, consecutive chemo-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) received pemetrexed 500mg/m(2), oxaliplatin 100mg/m(2) and bevacizumab 7.5mg/kg every 3 weeks for 6 cycles, in the outpatient setting. Maintenance therapy including pemetrexed and bevacizumab was given to patients with non-progressive disease. The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-eight patients (50% males, median age: 55 years, range 38-76) received a total of 199 cycles (median per patient: 6, range 2-6), plus 98 cycles of maintenance therapy. Twenty patients (52.6%) had a PS of 2, and 6 (15.8%) had brain metastases. The most frequent toxicities were hypertension (all grades: 42.1%) and peripheral neuropathy (grade 2-3: 21.1%). Haematological toxicities included grade 4 neutropenia, grade 3 anaemia and thrombopenia (5.3% each). Neither febrile neutropenia nor arterial thrombo-embolic event occurred. The objective response rate was 55.3% (95%CI: 39.5-71.1). The median PFS and OS were 6.2 (95%CI: 5.4-9.0) and 14.6 (95%CI: 9.8-19.5) months, respectively. CONCLUSIONS: In this single centre experience, the combination of pemetrexed, oxaliplatin and bevacizumab was well tolerated and had promising activity as first-line therapy in unselected patients with stage IV non-squamous NSCLC.