Chouaid Christos, Bosquet Lise, Knott Craig, Li Ziming, Schaeffer Marcy, Lin Xiwu, Schioppa Claudio A, Perualila Nolen Joy, Diels Joris, Caparros Eduardo Quintero, Galea Francesca, Hultén Annika, Greystoke Alastair
CHI Créteil, Créteil, France.
Unicancer, 101 rue de Tolbiac, 75013 Paris, France.
Lung Cancer. 2025 May;203:108548. doi: 10.1016/j.lungcan.2025.108548. Epub 2025 Apr 19.
In PAPILLON, frontline amivantamab + carboplatin + pemetrexed (ACP) demonstrated superior efficacy over carboplatin + pemetrexed in patients with advanced or metastatic non-small-cell lung cancer (aNSCLC) harboring mutations in epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins). Real-world (RW) treatment patterns and comparative effectiveness of ACP versus RW treatments are unknown.
The present study (NECTAR) retrospectively analyzed frontline treatments prescribed 2012-2023 for patients with aNSCLC and confirmed EGFR exon20ins from English (ENG-NCRD), French (FR-ESME), and US (US-COTA and US-ConcertAI) datasets. Overall survival (OS), time to next treatment (TTNT), and progression-free survival (PFS) were assessed in RW pooled and individual treatment classes and in indirect treatment comparisons (ITC) between ACP from PAPILLON and RW treatments using Cox proportional hazards model adjusted for prognostic factors.
NECTAR assessed 208 RW patients: ENG-NCRD, n = 23; FR-ESME, n = 91; US-COTA, n = 39, and US-ConcertAI, n = 55. Common frontline treatment classes were platinum-based chemotherapy (33.7 %), platinum + immunotherapy (23.1 %), EGFR tyrosine kinase inhibitors (TKIs) alone (15.4 %), platinum + VEGF inhibitors (VEGFi) (11.1 %), and immunotherapy alone (7.7 %). Compared with platinum-based chemotherapy, none of the evaluated treatment classes demonstrated improved OS, TTNT, and PFS. Exceptions were platinum + VEGFi in TTNT and PFS and platinum + immunotherapy in TTNT. In ITCs, ACP significantly improved OS over pooled RW treatments (HR = 0.48 [95 % CI, 0.32-0.71]; P < 0.001), platinum-based chemotherapy (HR = 0.48 [0.30-0.77]; P = 0.003), platinum + immunotherapy (HR = 0.41 [0.23-0.73]; P = 0.003), and EGFR TKI alone (HR = 0.48 [0.23-1.02]; P = 0.055). TTNT and PFS results were similar to OS.
In patients with EGFR exon20ins aNSCLC, frontline ACP was superior to common RW treatments, highlighting the need for practice change.
在“蝴蝶”（PAPILLON）研究中，对于携带表皮生长因子受体（EGFR）外显子20插入突变（exon20ins）的晚期或转移性非小细胞肺癌（aNSCLC）患者，一线使用阿米万他单抗+卡铂+培美曲塞（ACP）方案相较于卡铂+培美曲塞方案显示出更优的疗效。真实世界（RW）中的治疗模式以及ACP与RW治疗的对比疗效尚不清楚。
本研究（NECTAR）回顾性分析了2012年至2023年为aNSCLC且确诊EGFR exon20ins的患者开具的一线治疗方案，数据来自英文（ENG-NCRD）、法文（FR-ESME）以及美国（US-COTA和US-ConcertAI）数据集。使用针对预后因素进行调整的Cox比例风险模型，在RW汇总和个体治疗类别以及“蝴蝶”研究中的ACP与RW治疗的间接治疗比较（ITC）中评估总生存期（OS）、下次治疗时间（TTNT）和无进展生存期（PFS）。
NECTAR研究评估了208例RW患者：ENG-NCRD组23例，FR-ESME组91例，US-COTA组39例，US-ConcertAI组55例。常见的一线治疗类别为铂类化疗（33.7%）、铂类+免疫治疗（23.1%）、单独使用EGFR酪氨酸激酶抑制剂（TKI）（15.4%）、铂类+血管内皮生长因子抑制剂（VEGFi）（11.1%）以及单独使用免疫治疗（7.7%）。与铂类化疗相比，所评估的治疗类别均未显示出OS、TTNT和PFS的改善。TTNT和PFS方面的例外情况是铂类+VEGFi以及TTNT方面的铂类+免疫治疗。在ITC中，ACP相较于汇总的RW治疗显著改善了OS（风险比[HR]=0.48[95%置信区间，0.32 - 0.71]；P<0.001）、铂类化疗（HR=0.48[0.30 - 0.77]；P=0.003）、铂类+免疫治疗（HR=0.41[0.23 - 0.73]；P=0.003）以及单独使用EGFR TKI（HR=0.48[0.23 - 1.02]；P=0.055）。TTNT和PFS结果与OS相似。
对于EGFR exon20ins aNSCLC患者，一线ACP方案优于常见的RW治疗，这凸显了改变临床实践的必要性。
