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Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study.

Christos Chouaid·Lise Bosquet·Craig Knott·Ziming Li·Marcy Schaeffer·Xiwu Lin·Claudio A Schioppa·Nolen Joy Perualila·Joris Diels·Eduardo Quintero Caparros·Francesca Galea·Annika Hultén·Alastair Greystoke
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Abstract

INTRODUCTION: In PAPILLON, frontline amivantamab&#xa0;+&#xa0;carboplatin&#xa0;+&#xa0;pemetrexed (ACP) demonstrated superior efficacy over carboplatin&#xa0;+&#xa0;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. MATERIALS AND METHODS: 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. RESULTS: NECTAR assessed 208 RW patients: ENG-NCRD, n&#xa0;=&#xa0;23; FR-ESME, n&#xa0;=&#xa0;91; US-COTA, n&#xa0;=&#xa0;39, and US-ConcertAI, n&#xa0;=&#xa0;55. Common frontline treatment classes were platinum-based chemotherapy (33.7&#xa0;%), platinum&#xa0;+&#xa0;immunotherapy (23.1&#xa0;%), EGFR tyrosine kinase inhibitors (TKIs) alone (15.4&#xa0;%), platinum&#xa0;+&#xa0;VEGF inhibitors (VEGFi) (11.1&#xa0;%), and immunotherapy alone (7.7&#xa0;%). Compared with platinum-based chemotherapy, none of the evaluated treatment classes demonstrated improved OS, TTNT, and PFS. Exceptions were platinum&#xa0;+&#xa0;VEGFi in TTNT and PFS and platinum&#xa0;+&#xa0;immunotherapy in TTNT. In ITCs, ACP significantly improved OS over pooled RW treatments (HR&#xa0;=&#xa0;0.48 [95&#xa0;% CI, 0.32-0.71]; P&#xa0;<&#xa0;0.001), platinum-based chemotherapy (HR&#xa0;=&#xa0;0.48 [0.30-0.77]; P&#xa0;=&#xa0;0.003), platinum&#xa0;+&#xa0;immunotherapy (HR&#xa0;=&#xa0;0.41 [0.23-0.73]; P&#xa0;=&#xa0;0.003), and EGFR TKI alone (HR&#xa0;=&#xa0;0.48 [0.23-1.02]; P&#xa0;=&#xa0;0.055). TTNT and PFS results were similar to OS. CONCLUSIONS: In patients with EGFR exon20ins aNSCLC, frontline ACP was superior to common RW treatments, highlighting the need for practice change.

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HumansCarcinoma, Non-Small-Cell LungLung NeoplasmsMaleFemaleErbB ReceptorsAntineoplastic Combined Chemotherapy ProtocolsMiddle AgedAgedRetrospective StudiesExonsPemetrexedCarboplatinMutationPrognosisMutagenesis, InsertionalAdultAged, 80 and overAmivantamabEGFR mutationsNSCLCRWEexon 20 insertionsexon20insJournal ArticleComparative StudyResearch Support, Non-U.S. Gov't

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Christos Chouaid, Lise Bosquet, Craig Knott, Ziming Li, Marcy Schaeffer, Xiwu Lin, Claudio A Schioppa, Nolen Joy Perualila, Joris Diels, Eduardo Quintero Caparros, Francesca Galea, Annika Hult&#xe9;n, Alastair Greystoke. 2025-04-19. Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study.. https://doi.org/10.1016/j.lungcan.2025.108548

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