A phase II trial of first-line bevacizumab in combination with pemetrexed and carboplatin in advanced nonsquamous non-small cell lung cancer (NSCLC)

Abstract

e19091 Background: Combining bevacizumab (Bev) with platinum doublet yields a survival benefit in previously untreated patients with advanced nonsquamous non-small cell lung cancer. Carboplatin with pemetrexed is an efficient combination that is potentially less toxic. This phase II trial evaluates the efficacy and the safety of adding bevacizumab to carboplatin and pemetrexed in advanced non-small cell lung cancer. Methods: This is a single arm, open-label phase II trial. Eligibility stipulated enrollment of patients with stage IIIB/IV non-squamous non-small cell lung cancer with an ECOG PS 0–1 and no other contraindications to Bev. Treatment consisted of pemetrexed 500 mg/m2, carbo AUC 6 and Bev 15mg/kg on day 1, repeated every 3 weeks. If clinical benefit was proven, patients received Bev maintenance until progression. The response was evaluated every two cycles. The primary endpoint was time to progression (TTP); secondary endpoints included overall survival, response rate (RR) and grade 3–4 toxicities. Results: As of September 2008, 27 out of 42 projected patients were enrolled of which, 14 were males and 13 females; median age 68 (72% older than 60); IIIB/IV 5/22; median number of cycles 9 (range 2–33). At the time of analysis, 25 patients were evaluable. Preliminary results show a median time to progression of 7.25 months (95% CI, 6.4 to 8.2). 23 patients (92%) had disease control (95%, CI 82–96%) with an overall response rate of 36% (95%, CI 25–47%).14 patients had stable disease (56%), 8 had partial response (32%) and one achieved a complete response (4 %). Median survival has not yet been reached. Grade 3/4 adverse events include: Cerebral ischemic event (N=1), Anorexia (Gr 3: N= 5/ Gr 4: N= 4), gastrointestinal fistula (N=1), hypertension (Gr3: N=3), epistaxis (Gr 3 N=1), vomiting (Gr 3; N= 3), fever (Gr 4: N=1) and neuropathy (Gr 3: N=2). Conclusion: The addition of bevacizumab to carboplatin and pemetrexed appears to be an active first line treatment with a high disease control rate and an acceptable toxicity profile in the setting of advanced non-small cell lung cancer. No significant financial relationships to disclose.