A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

Abstract

Bevacizumab with platinum doublet therapy including paclitaxel+carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel+carboplatin led to Grade>3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel+carboplatin + bevacizumab combination in a Japanese population. Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6cycles of carboplatin (area under the concentration-time curve=6 on Day 1)+nanoparticle albumin-bound paclitaxel (100mg/m2 on Days 1, 8 and 15)+bevacizumab (15mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel+bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade≥3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.