Clinical Outcomes Beyond 1L EGFR-TKI Progression in mNSCLC: Final Results of the Real-World Study 'LUNGFUL'

Giannis Mountzios; Anna Koumarianou; Helena Linardou; Anastasios Boutis; Dimitrios Mavroudis; Epaminondas Samantas; Ippokratis Korantzis; Elias Athanasiadis; Evangelos G Fergadis; Sofia Lampaki; Vassilis Georgoulias; Sofia Baka; Michalis V Karamouzis; Ioannis Boukovinas; Charalampos Andreadis; Aggeliki Rapti; Nikolaos Koulouris; George Pentheroudakis; Marios E Froudarakis; Alvertos Somarakis; Eleftheria Anastasopoulou; Alexandra Karadimou; Foteini Papageorgiou; Zoe Paparepa; Aristeidis Nikolaou; Christina Papista; Konstantinos N Syrigos

doi:10.21873/anticanres.16388

Clinical Outcomes Beyond 1L EGFR-TKI Progression in mNSCLC: Final Results of the Real-World Study 'LUNGFUL'

Anticancer Res. 2023 May;43(5):2243-2258. doi: 10.21873/anticanres.16388.

Authors

Giannis Mountzios¹, Anna Koumarianou², Helena Linardou³, Anastasios Boutis⁴, Dimitrios Mavroudis⁵, Epaminondas Samantas⁶, Ippokratis Korantzis⁷, Elias Athanasiadis⁸, Evangelos G Fergadis⁹, Sofia Lampaki¹⁰, Vassilis Georgoulias¹¹, Sofia Baka¹², Michalis V Karamouzis¹³, Ioannis Boukovinas¹⁴, Charalampos Andreadis¹⁵, Aggeliki Rapti¹⁶, Nikolaos Koulouris¹⁷, George Pentheroudakis¹⁸, Marios E Froudarakis¹⁹, Alvertos Somarakis²⁰, Eleftheria Anastasopoulou²⁰, Alexandra Karadimou²⁰, Foteini Papageorgiou²¹, Zoe Paparepa²², Aristeidis Nikolaou²⁰, Christina Papista²⁰, Konstantinos N Syrigos²³

Affiliations

¹ Fourth Oncology Department and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece; [email protected].
² Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
³ 4 Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital, Athens, Greece.
⁴ First Department of Clinical Oncology, Theagenio Hospital, Thessaloniki, Greece.
⁵ Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.
⁶ 2 Oncology Department, Metropolitan Hospital, Athens, Greece.
⁷ Oncology Department, "Saint Luke" Private Hospital, Thessaloniki, Greece.
⁸ Department of Medical Oncology, Mitera Hospital, Athens, Greece.
⁹ Medical Oncology Department, Metaxa Cancer Hospital, Piraeus, Greece.
¹⁰ Pulmonary Department, General Hospital 'G. Papanikolaou', Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹¹ First Department of Medical Oncology, Metropolitan General, Athens, Greece.
¹² Oncology Department, "Interbalkan" European Medical Center, Thessaloniki, Greece.
¹³ Molecular Oncology Unit, Department of Biological Chemistry Medical School, Athens, Greece.
¹⁴ BIOCLINIC of Thessaloniki, Thessaloniki, Greece.
¹⁵ Second Department of Clinical Oncology, Theagenio Hospital, Thessaloniki, Greece.
¹⁶ Second Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Sotiria Hospital, Athens, Greece.
¹⁷ First Department of Respiratory Medicine, National & Kapodistrian University of Athens Medical School, "SOTIRIA" Hospital for Chest Diseases, Athens, Greece.
¹⁸ Department of Medical Oncology, Medical School University of Ioannina, Ioannina, Greece.
¹⁹ Department of Respiratory Medicine, Medical School of Alexandroupolis Democritus University of Thrace, Alexandroupolis, Greece.
²⁰ Medical Affairs Department, AstraZeneca, Athens, Greece.
²¹ Diagnostics Function Oncology, AstraZeneca, Athens, Greece.
²² Clinical Operations, AstraZeneca, Athens, Greece.
²³ Third Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Sotiria Hospital, Athens, Greece.

PMID: 37097667
DOI: 10.21873/anticanres.16388

Abstract

Background/aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed.

Patients and methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting.

Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment.

Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.

Keywords: Biopsy; EGFR-tyrosine kinase inhibitor; T790M mutation; epidermal growth factor receptor; non-small-cell lung cancer.

Publication types

Observational Study

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
ErbB Receptors / genetics
ErbB Receptors / therapeutic use
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Mutation
Protein Kinase Inhibitors / therapeutic use

Substances

ErbB Receptors
Protein Kinase Inhibitors
EGFR protein, human