Phase II Study of Paclitaxel, Carboplatin, and Cetuximab as First Line Treatment, for Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Results of OPN-017

Background: Cetuximab has demonstrated synergy with taxanes in preclinical models; as well as single agent activity. We assessed the activity of cetuximab with carboplatin and paclitaxel given on a 4-week schedule, in advanced, chemo-naive non-small cell lung cancer. Patients and Methods: This phase II, single arm, multi-institution day 1, then Study featured standard dosage of cetuximab 400 mg/m(2) 250 mg/m(2) with paclitaxel (100 mg/m(2)/wk, For 3 weeks), and carboplatin (area under curve = 6) day 1 of each 28 clay cycle. After 4 to 6 cycles, in the absence of disease progression or excess toxicity, cetuximab was Continued weekly. Primary end point was response rate. Results: Fifty-three patients (median age 63, 51% male) participated. Response rate was 57% (3 complete response and 27 partial response). At a median follow-up of 12.5 months, the estimated overall Survival is 13.8 months (95% CI: 9.08-16.02) with an event-free survival rate of 5.53 months (95% CI: 4.77-7.99) 18.9% remain free from progression at 1 year. Improved survival was associated with female gender, absence of prior radiation, PS 0 and epidermal growth factor receptor expression. Toxicities included rash (28% grade 3), nail changes (3.7% grade 3). hypomagnesemia (7.5% grade 3 and 3.7% grade 4), and neutropenia (25% grade 3 and 13% grade 4) in addition to other typical side effects anticipated with paclitaxel/carboplatin. There were no grade 5 toxicities. Conclusion: Combination of cetuximab/paclitaxel/carboplatin in non-small cell lung cancer was well tolerated and clinically active with manageable toxicities. This unique schedule, integrating weekly paclitaxel and cetuximab has not yet been tested in a randomized trial.