Cetuximab (Erbitux®, Eli Lilly and Company)

Compared to bevacizumab, fewer clinical trials were conducted to evaluate the efficacy and/or safety of cetuximab in the treatment of lung cancer. Results from the phase 3 FLEX trial demonstrated a modest but statistically significant survival benefit with chemotherapy plus cetuximab compared with chemotherapy alone (hazard ratio [HR] 0.871, 95% CI 0.762–0.996; P=0.044) as first-line treatment for patients with EGFR-expressing NSCLC.7

The FLEX trial results were published in 2009. In a later study, published in early 2012, data from the FLEX trial were analyzed retrospectively to determine if the level of EGFR expression impacted survival.8 The investigators reported that high EGFR expression (ie, overexpression) was observed in 345 (31%) evaluable patients and low expression was observed in 776 (69%) patients. For the overexpressing cohort, median overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (12 months [95% CI 10.2–15.2] vs 9.6 months [7.6–10.6]; HR 0.73, 0.58–0.93; P = 0.011). These results suggested that NSCLC patients that overexpress EGFR would benefit more from treatment with cetuximab as first-line therapy.   

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Another trial evaluated the possibility of adding cetuximab to regimens containing pemetrexed in patients with recurrent or progressive NSCLC who had completed platinum-based therapy. Results of this phase 3 trial, known as SELECT, were presented at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting.9 In this study, the investigators sought to improve progression-free survival in this patient population that had previously failed platinum-based therapy.

In this multi-center, open-label, randomized phase 3 trial, patients received either pemetrexed (500mg/m2; n = 605) or docetaxel (75mg/m2; n = 333) on day 1, and were then randomized within each group to chemotherapy (pemetrexed or docetaxel) plus cetuximab (400/250mg/m2) or chemotherapy alone. Therapy was administered in six 3-week cycles. PFS results were reported for pemetrexed-cetuximab (PC) vs pemetrexed (P) only, not for docetaxel. Patients were followed until the primary end point of progression-free survival (PFS) for PC vs. P was reached; secondary end points were overall survival (OS), objective response rate (ORR), and duration of response (DOR).

No difference in median PFS was observed: 2.89 months for the PC-arm vs. 2.76 months for pemetrexed arm (HR = 1.03 [95% CI=0.87–1.21]; P = 0.76). A similar result was observed for median OS: 6.93 months for PC vs. 7.79 months for pemetrexed (HR = 1.01 [95% CI=0.86–1.20]; P = 0.86). ORR for PC was 6.6% vs. 4.3% for pemetrexed (odds ratio = 1.59 [95% CI = 0.78–3.26]; P = 0.20). Median DOR for PC was 4.17 months vs. 6.93 months for pemetrexed (HR = 1.58 [95% CI = 0.74–3.36]; P = 0.24).