Department of pneumology, hôpital Saint-Joseph, 75014 Paris, France.
Multidisciplinary oncology and therapeutic innovations department, centre hospitalier universitaire de Marseille, 13000 Marseille, France.
Cancer Radiother. 2022 Sep;26(5):670-677. doi: 10.1016/j.canrad.2021.12.005. Epub 2022 Mar 5.
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.
Eligible patients received weekly cetuximab (loading dose 400mg/m day 1; subsequent weekly 250mg/m doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m) and pemetrexed (500mg/m), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint.
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 35.8months (95% CI: 23.5-NR), and median progression-free survival 14.4months (95% CI: 11.2-18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%.
These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.
约 20%的非小细胞肺癌患者表现为局部晚期、不可切除的 III 期疾病。顺铂为基础的同期放化疗是主要治疗方法，随后是维持免疫治疗，但长期预后较差。这项 II 期试验（IFCT-0803）旨在评估在顺铂和培美曲塞放化疗中加入西妥昔单抗是否能提高这些患者的疗效。
符合条件的患者每周接受西妥昔单抗（负荷剂量 400mg/m2，第 1 天；随后每周 250mg/m2，直至放疗后两周）。化疗包括顺铂（75mg/m2）和培美曲塞（500mg/m2），均在 21 天周期的第 1 天给予，最多 4 个周期。放疗从第 22 天开始，最大剂量为 66Gy。16 周时的疾病控制率是主要终点。
共纳入 106 例患者（99 例符合条件的患者）。化疗周期 1 至 4 天 1 日的依从性超过 95%，76%的患者接受了 12 个计划的西妥昔单抗剂量。最大 3 级毒性发生在 63%的患者中，最大 4 级毒性发生在 9.6%的患者中。涉及前 95 例合格患者的主要终点包括 2 例（2.1%）完全缓解，57 例（60.0%）部分缓解，27 例（28.4%）稳定疾病。这一 90.5%的疾病控制率（95%置信区间[95%CI]：84.6%-96.4%）在 16 周时达到。中位随访 63.0 个月后，1 年和 2 年生存率分别为 75.8%和 59.5%。中位总生存期为 35.8 个月（95%CI：23.5-NR），中位无进展生存期为 14.4 个月（95%CI：11.2-18.8），1 年和 2 年无进展生存率分别为 57.6%和 34.3%。
这些生存率与已发表的数据相比具有优势，因此支持进一步开发以西妥昔单抗为基础的诱导放化疗。
