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. 2021 Aug 2;13(15):3887.
doi: 10.3390/cancers13153887.

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

Valéry Refeno  1   2   3 , Michele Lamuraglia  1   4 , Safae Terrisse  5 , Clément Bonnet  5 , Clément Dumont  5 , Ludovic Doucet  6 , Damien Pouessel  7 , Stephane Culine  5
Affiliations

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era

Valéry Refeno et al. Cancers (Basel). .

Abstract

Background: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment.

Methods: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line.

Results: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53-37.6) and the median follow-up duration was 40.83 months (range 11.33-88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line.

Conclusions: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

Keywords: EGFR-genes; TKI; drug therapy; lung cancer; metastasis; survival analysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Selection of patients included in the study.
Figure 2
Figure 2
PFS according to the treatment received in third-line (a) and according to the pattern of treatment (b). PFS according to the choice of third-line for patient which received CT in second-line (c) and received TKI in second-line (d). (e,f) represent respective PFS according to choice of second-line for patient which received TKI in third-line and CT in third-line.
Figure 3
Figure 3
OS according to the treatment received in third-line (a), according to the pattern of treatment (b), according to the choice of third-line for patient which received CT in second-line (c) and according to the choice of third-line for patient who received TKI in second-line (d). (e,f) represent respective OS according to choice of second-line for patient which received TKI in third-line and CT in third-line.
Figure 4
Figure 4
OS according to the presence or absence of the exon 21 mutation.
See this image and copyright information in PMC

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