Phase II trial of cetuximab (C225) in combination with monthly carboplatin (Cb) and weekly paclitaxel (Pac) in patients with advanced NSCLC: Promising early results.

8104 Background: C225, a monoclonal antibody targeting epidermal growth factor receptor and standard q 3 week PacCb yielded a median survival of nearly 11 months in a large phase II SWOG trial (Thienelt, JCO, 2005). We mounted a phase II trial of C225 in combination with monthly Cb and weekly Pac, to capitalize on potential synergy between taxane and C225, and to mitigate taxane-induced neuropathy.,Enrollees received Cb AUC 6 day 1, Pac 100 mg/m2 days 1, 8, and 15 every 4 weeks, and C225 400 mg/m2 d1, then 250 mg/m2 Q wk. In patients without disease progression or limiting toxicity, C225 was continued as a single agent after 6 full cycles of therapy. Eligibility stipulated advanced NSCLC (Stage IV, 'wet' IIIB or recurrence after prior surgery/radiation); ECOG performance status 0-1; measurable tumor, and adequate physiologic indices.,53 patients were accrued: median age 63 years (range, 41 to 86); 51% male, 85% Caucasian; 47% Performance Status-0; 15% prior RT. 31 pts (58%) had sufficient tissue for EGFr (IHC); 87% proved (+), 32% were 3+. Overall response rate (RR) was 57% including 3 CR. 23% had stable disease as best response. Median time to progression (TTP) was 5.5 months (18 patients), Median survival was 13.8 mos; 1 yr OS 53%, 2 yr OS 18%. 13 completed 6 cycles and went onto maintenance therapy with C225 alone. Respective MS for men and women was 7.6 and 16.1 mo (p=0.003), for prior RT vs none, 6.1 and 14.1 mo (p=0.0056), and PS 0 vs 1, 7.6 and 16.0 mo (p=0.0173). Age had no bearing on outcome. Those without EGFr expression did worse (p=0.03). Chief grade 3 and 4 toxicities included neutropenia in 20, HSR in 3, fatigue in 8, sensory neuropathy in 5, hypomagnesemia in 6 and rash in 15. Cumulative paronychia, nail lysis, and digital fissures frequently led to cessation of maintenance therapy Conclusions: C225 in combination with monthly Cb and weekly Pac is highly active in advanced NSCLC. Response and survival data are promising, the best we have observed to date in the Fox Chase Cancer Center Extramural Research Program through the Oncology Physician Network. [Table: see text].