A phase II study of cetuximab (C225) in combination with chemoradiation (CRT) in patients (PTS) with stage IIIA/B non-small cell lung cancer (NSCLC): A report of the 2 year and median survival (MS) for the RTOG 0324 trial

Abstract

7516 Background: C225 is a chimerized monoclonal antibody that targets the epidermal growth factor receptor (EGFR). NSCLC commonly expresses the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Preclinical model systems demonstrate radiosensitization following molecular inhibition of EGFR signaling. Methods: We report a phase II trial testing the combination of C225 with CRT in unresectable stage III NSCLC with a planned sample size of 84 PTS. Eligibility criteria included Zubrod performance status (PS) ≤ 1, weight loss ≤ 5% over past 3 months, FEV1 ≥ 1.2 L, adequate hematologic, hepatic, and renal function. PTS received an initial dose of C225 (400 mg/m2) on day 1 of wk 1, then wkly doses of C225 (250 mg/m2) until completion of therapy (wks 2 - 17). During wk 2, PTS started CRT (63 Gy/35 fractions) with wkly carboplatin (C) AUC 2 and paclitaxel (P) 45 mg/m2 x 6 doses followed by C (AUC 6) and P (200 mg/m2) x 2 cycles (wks 12–17). Interim monitoring for severe (grade ≥ 3) or excessive non-hematologic toxicities occurred after PTS had been treated and followed for at least 90 days after RT. Primary endpoints include safety and compliance of concurrent C225 and CRT. Results: 93 PTS were enrolled with 87 evaluable PTS. PTS characteristics: 57% male, median age 64 years (range 42–85), 47% PS 0, 46% stage IIIA. Median follow-up is 21.6 months (M). Response rate is 62% (n=54), MS is 22.7 M, and 24 M overall survival (OS) is 49.3%(# at risk=40). Adverse events related to treatment include 20%(n=17) of PTS with grade (G) 4 hematologic toxicities, 8% (n=7 PTS) G 3 esophagitis, and 7% (n=6 PTS) G 3–4 pneumonitis. There were 5 G 5 events. Conclusions: The combination of C225 with CRT is feasible and active with MS and OS better than any previously reported by the RTOG. These results warrant confirmation in a randomized trial. Complete compliance, toxicity, and updated survival data will be reported. Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI. This abstract's contents are the sole responsibility of the authors and do not necessarily represent the official views of the NCI. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Incorporated Bristol-Myers Squibb, ImClone Systems Incorporated Bayer, Bristol-Myers Squibb, Eli Lilly