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A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes

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Abstract

Background

In Europe, few data regarding the characteristics of EGFR exon 20 insertion (20ins) mutations in non-small cell lung cancer (NSCLC) are available.

Objective

Using a large real-world cohort, we assessed the incidence, characteristics, and outcomes of patients with non-squamous (nsq) NSCLC harboring EGFR exon 20ins.

Patients and Methods

The Epidemio-Strategy and Medical Economics advanced and metastatic lung cancer data platform including advanced/metastatic nsqNSCLC patients from January 2015 was analyzed (cut-off date: June 30, 2020). Characteristics, epidermal growth factor receptor (EGFR) mutation and other mutations, treatment patterns, and clinical outcomes were assessed for patients harboring EGFR exon 20ins, common EGFR mutations, other EGFR mutations, and wild-type EGFR. Survival parameters were estimated by the Kaplan-Meier method in these four groups.

Results

Out of 9435 nsqNSCLC patients tested for EGFR, 1549 (16.4%) had a mutation, including 61 with EGFR exon 20ins (3.9% of all mutated EGFR). These 61 patients had a mean age of 63.6 years, were mostly female (68.9%) and non-smokers (55.7%), with de novo stage IV disease (73.8%) and performance status 0–1 (76.9%). Almost all patients (95.1%) with exon 20ins received systemic therapy (median, three lines). First-line systemic treatments consisted mainly of combination chemotherapy (70.7%), single-agent EGFR tyrosine kinase inhibitors (10.3%), and single-agent immunotherapy (5.2%). After a median follow-up of 25.0 (95% confidence interval [CI] 22.3–32.4) months, the median real-world overall survival was 24.3 (19.1–32.6) months in patients with exon 20ins compared to 35.4 (95% CI 32.6–37.5) in patients with common EGFR mutation (n = 1049) (p = 0.049) and 19.6 (95% CI 18.6–20.5) in patients with wild-type EGFR (n = 7866) (p = 0.2).

Conclusions

This large national study in nsqNSCLC patients confirms that EGFR exon 20ins is a rare condition (0.6%). The prognosis associated with exon 20ins appears to be in line with that of wild-type EGFR, but worse than common EGFR mutations, highlighting the need for advancements for this rare population.

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Acknowledgements

We thank the 30 health facilities involved in the ESME ALMC database as of June 30, 2020 for providing the data and each ESME local coordinator for managing the project at local level: Centre François Baclesse, Caen; Institut de Cancérologie de l’Ouest, Angers/Nantes; Centre Leon Bérard, Lyon, Institu Curie, Paris/ Saint-Cloud; Centre Antoine Lacassagne, Nice; Centre Jean Perrin, Clermont Ferrand; Centre Oscar Lambret, Lille; Institut Claude Regaud, Toulouse; Centre Hospitalier Régional Universitaire, Tours; Centre Georges-François Leclerc, Dijon; Institut Paoli-Calmettes, Marseille; Centre Paul Strauss, Strasbourg; Institut de Cancérologie de Lorraine, Nancy; Gustave Roussy, Villejuif; Centre Hospitalier Intercommunal, Créteil; Centre Hospitalier, Mulhouse; Institut Bergonié, Bordeaux; Institut Jean Godinot, Reims; Centre Hospitalier Métropole Savoie, Chambery; Centre Henri Becquerel, Rouen; Centre Hospitalier, Côte Basque, Bayonne; Centre Hospitalier Universitaire, Rennes; Centre Hospitalier Sainte-Musse, Toulon; Centre Hospitalier, Départemental de Vendée, La Roche-sur-Yon; Institut de Cancerologie Mutualiste, Montpellier; HEM, Marseille; Centre Hospitalier, Annecy-Genevois, Annecy; Centre Hospitalier, Saint-Quentin; Centre Hospitalier Universitaire, d’Angers. Moreover, we thank the ESME Scientific Committee members for their ongoing support.

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Authors and Affiliations

  1. Service de Pneumologie, Pneumology, Intercommunal Hospital, 40 avenue de Verdun, 94010, Créteil, France

    Christos Chouaid

  2. Institut Claudius Regaud, Toulouse, France

    Thomas Filleron

  3. GHRMSA, Emile Muller Hospital, Mulhouse, France

    Didier Debieuvre

  4. Centre Léon Bérard, Lyon, France

    Maurice Pérol

  5. Institut Curie, Paris, France

    Nicolas Girard

  6. Centre Oscar Lambret, Lille, France

    Eric Dansin

  7. University Hospital, Rennes, France

    Hervé Lena

  8. Centre François Baclesse, Caen, France

    Radj Gervais

  9. Institut Bergonié, Bordeaux, France

    Sophie Cousin

  10. Centre Antoine Lacassagne, Nice, France

    Josiane Otto

  11. Institut de Cancérologie Strasbourg Europe ICANS, Strasbourg, France

    Roland Schott

  12. Gustave Roussy, Villejuif, France

    David Planchard

  13. Institut Paoli-Calmettes, Marseille, France

    Anne Madroszyk

  14. Centre Georges-François Leclerc, Dijon, France

    Courèche Kaderbhai

  15. Centre Jean Perrin, Clermont-Ferrand, France

    Pascale DUBRAY-Longeras

  16. Institut de Cancérologie de l’Ouest, Angers, Nantes, France

    Sandrine Hiret

  17. University Hospital, Tours, France

    Eric Pichon

  18. Institut de Cancérologie de Lorraine, Nancy, France

    Christelle Clément-Duchêne

  19. Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine, Nancy, France

    Christelle Clément-Duchêne

  20. IQVIA, La Defense, Cedex, France

    Gaëlle Chenuc

  21. Real-world Data, Unicancer, Paris, France

    Gaëtane Simon & Lise Bosquet

  22. Institut Régional du Cancer de Montpellier, Montpellier, France

    Xavier QUantin

Authors
  1. Christos Chouaid
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  2. Thomas Filleron
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  3. Didier Debieuvre
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  4. Maurice Pérol
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  5. Nicolas Girard
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  6. Eric Dansin
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  7. Hervé Lena
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  8. Radj Gervais
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  9. Sophie Cousin
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  10. Josiane Otto
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  11. Roland Schott
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  12. David Planchard
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  13. Anne Madroszyk
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  14. Courèche Kaderbhai
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  15. Pascale DUBRAY-Longeras
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  16. Sandrine Hiret
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  17. Eric Pichon
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  18. Christelle Clément-Duchêne
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  19. Gaëlle Chenuc
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  20. Gaëtane Simon
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  21. Lise Bosquet
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  22. Xavier QUantin
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Corresponding author

Correspondence to Christos Chouaid.

Ethics declarations

Funding

The ESME AMLC database receives financial support from an industrial consortium (AstraZeneca, MSD, BMS, Janssen, Amgen, and Roche). Data collection, analysis, and publication are fully managed by Unicancer independently of the industrial consortium.

Conflicts of interest

CC: Grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Sanofi, BMS, MSD, Lilly, Novartis, Takeda, Bayer, and Amgen. TF received fees from Cellectis that were compensated by his institution. DD: No conflict of interest. MP: Grants, personal fees, and non-financial support from AstraZeneca, Roche, Boehringer Ingelheim, and Takeda, outside the submitted work. NG: Research/grant support from MS, AstraZeneca, AbbVie, Amgen, Boehringer-Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, and Trizell and consultative services for BMS, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, and Sivan. ED: No conflict of interest. HL: Consulting fees from BMS, AstraZeneca, Takeda, Roche, Pfizer, Novartis, and Lilly. JO: No conflict of interest. DP: Consulting, advisory role or lectures for AstraZeneca, AbbVie, Bristol-Myers Squibb, Celgene, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung, and Janssen; travel, accommodation, and expenses for meetings for AstraZeneca, Roche, Novartis, prIME Oncology, and Pfizer; and advisory role for AstraZeneca, AbbVie, Bristol-Myers Squibb, Celgene, Merck, Novartis, Pfizer, Roche, Samsung, and Janssen. CK: No conflict of interest. SH: Fees from Takeda and AstraZeneca to participate in review activities. EP: Consulting fees from Roche, Astra Zeneca, BMS, MSD, and Takeda and support for meetings from Takeda and MSD. CCD: No conflict of interest. GC: No conflict of interest. GS: No conflict of interest. LB: No conflict of interest. XQ: No conflict of interest. RG, SC, RS, AM, and PDL did not report conflicts of interest.

Ethics approval

Unicancer manages the ESME AMLC data platform in accordance with current best practice guidelines. In compliance with French regulations, the ESME data platform was authorized by the French data protection authority (initial authorization no. DE-2017-397 and subsequent amendment dated October 14, 2019 in accordance with General Data Protection Regulation). Data are updated on a yearly basis and run into a data-management process aimed at ensuring the quality of the data analyzed.

Informed consent

Not applicable.

Data availability

Individual participant data that underlie the reported results will not be made available.

Authors’ contributions

Conceptualization: CC, TF, DD, and XQ. Formal analysis: GC. Methodology: CC, TF, DD, GS, LB, and XQ. Project administration: GS and LB. Resources: GS and LB. Software: GC. Supervision: CC, TF, DD, and XQ. Validation: GS and LB. Visualization: GC. Writing—original draft: CC and LB. Writing—review and editing: TF, DD, MP, NG, ED, HL, RG, SC, JO, RS, DP, AM, CK, PDL, SH, EP, CCD, LB, and XQ.

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Chouaid, C., Filleron, T., Debieuvre, D. et al. A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes. Targ Oncol 16, 801–811 (2021). https://doi.org/10.1007/s11523-021-00848-9

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  • DOI: https://doi.org/10.1007/s11523-021-00848-9

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