Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer

Purpose: Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. Materials and methods: Eligible patients received weekly cetuximab (loading dose 400 mg/m² day 1; subsequent weekly 250 mg/m² doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75 mg/m²) and pemetrexed (500 mg/m²), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66 Gy started on day 22. Disease control rate at week 16 was the primary endpoint. Results: One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%–96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8 months (95% CI: 23.5–NR), and median progression-free survival 14.4 months (95% CI: 11.2–18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. Conclusion: These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.