Lessons learned: This single-arm, phase II study shows that concurrent EGFR-tyrosine kinase inhibitor plus thoracic radiotherapy as the first-line treatment for stage IV non-small cell lung cancer harboring EGFR active mutations provides long-term control for the primary lung lesion, and 1-year progression-free survival (PFS) rate and median PFS are numerically higher than those of the erlotinib monotherapy.Serious adverse events are acceptable, although grade >3 radiation pneumonitis occurred in 20% of patients.
Background: Studies show effective local control by EGFR-tyrosine kinase inhibitor (TKI) combined with radiotherapy at metastatic sites in advanced lung cancer harboring EGFR active mutations. Salvage local radiotherapy is associated with prolonged progression-free survival (PFS) in local disease during EGFR-TKI treatment. However, no prospective study has been reported on concurrent EGFR-TKI and radiotherapy for primary lung lesions. This study investigated the efficacy and safety of first-line EGFR-TKI combined with thoracic radiotherapy in treating stage IV non-small cell lung cancer (NSCLC) harboring EGFR active mutations.
Methods: We conducted a single-arm, phase II clinical trial. Each patient received EGFR-TKI (erlotinib 150 mg or gefitinib 250 mg per day) plus thoracic radiotherapy (54-60 Gy/27-30 F/5.5-6 w) within 2 weeks of beginning EGFR-TKI therapy until either disease progression or intolerable adverse events (AEs) appeared.
Results: From January 2015 to March 2018, 401 patients were screened, and 10 patients (5 male and 5 female) were eligible. These patients had a median age of 55 years (40-75) and median follow-up of 19.8 months (5.8-34). The 1-year PFS rate was 57.1%, median PFS was 13 months, and median time to progression of irradiated lesion (iTTP) was 20.5 months. Objective response rate (ORR), was 50% and disease control rate (DCR) was 100%. The most common grade ≥3 AEs were radiation pneumonitis (20%) and rash (10%). One patient died after rejecting treatment for pneumonitis. The others received a full, systematic course of glucocorticoid therapy. Pneumonitis was all well controlled and did not relapse.
Conclusion: Concurrent EGFR-TKI plus thoracic radiotherapy as the first-line treatment for stage IV NSCLC harboring EGFR active mutations shows a long-term control of primary lung lesion. The 1-year PFS rate and median PFS of this combined therapy are numerically higher than those of the erlotinib monotherapy. The risk of serious adverse events is acceptable.
经验总结
本项研究为单臂 II 期研究，结果表明胸部放疗联合 EGFR‐酪氨酸激酶抑制剂在 EGFR 活性突变的 IV 期非小细胞肺癌患者一线治疗中，可以长期控制原发肺病灶，而且 1 年无进展生存 (PFS) 率和中位 PFS 高于厄洛替尼单药治疗。
严重不良事件的发生率可接受，尽管3 级以上放射性肺炎发生率为 20%。
摘要
背景。研究表明，EGFR 酪氨酸激酶抑制剂 (TKI) 联合放疗可有效局部控制 EGFR 活性突变的晚期肺癌转移部位。在 EGFR‐TKI 治疗过程中，挽救性局部放疗可延长局部疾病的无进展生存期 (PFS)。然而，目前还没有 EGFR‐TKI 联合放疗治疗原发肺病灶的前瞻性研究报道。本研究探讨了 EGFR‐TKI 联合胸部放疗在 EGFR 活性突变的 IV 期非小细胞肺癌 (NSCLC) 一线治疗中的疗效和安全性。
方法。研究为单臂 II 期临床试验。所有患者在开始 EGFR‐TKI 治疗后 2 周内接受 EGFR‐TKI(每天厄洛替尼 150 mg或 吉非替尼250 mg)联合胸部放疗(54‐60 Gy/ 27‐30 F/ 5.5‐6 w)，直到出现疾病进展或无法忍受的不良事件 (AE)。
结果。筛查 2015 年 1 月至 2018 年 3 月期间的 401 例患者，其中 10 例患者符合条件(男性 5 例，女性 5 例)。这些患者的中位年龄为 55 岁(40‐75 岁)，中位随访时间为 19.8 个月(5.8‐34 个月)。1 年 PFS 率为 57.1%，中位 PFS 为 13 个月，中位放射病灶至进展时间 (iTTP) 为 20.5 个月。客观有效率 (ORR) 为 50%，疾病控制率 (DCR) 为 100%。最常见的 3 级以上AE为放射性肺炎 (20%) 和皮疹 (10%)。1 例患者在拒绝接受肺炎治疗后死亡。其他患者接受了完整、系统的糖皮质激素治疗。肺炎得到很好的控制，没有复发。
结论。EGFR‐TKI 联合胸部放疗在 EGFR 活性突变的 IV 期 NSCLC 患者一线治疗中，可以长期控制原发肺病灶。这种联合疗法的 1 年 PFS 率和中位 PFS 数值上高于厄洛替尼单药治疗。严重不良事件的发生率可接受。
Trial registration: ClinicalTrials.gov NCT02353741.
© AlphaMed Press; the data published online to support this summary are the property of the authors.