Cancer Res Treat.  2022 Jul;54(3):817-826. 10.4143/crt.2021.822.

The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non–Small Cell Lung Cancer

• Kang N
• Kim KH
• Jeong BH
• Lee K
• Kim H
• Kwon OJ
• Ahn MJ
• Cho J
• Lee HY
• Um SW

• KMID: 2531327
• DOI: http://doi.org/10.4143/crt.2021.822

Abstract

Purpose
The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).
Materials and Methods
Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).
Results
A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).
Conclusion
Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Keyword

EGFR-TKI; Subsolid nodule; Ground-glass nodule; Non-small-cell lung carcinoma; Size

Figure

• 

  Fig. 1 A schematic flow chart of size changes in the SSNs according to initial EGFR-TKI and subsequent therapies. EGFR-TKI, epidermal growth factor receptor–tyrosine kinase inhibitor; SSN, subsolid nodule. a)The initial EGFR-TKIs were gefitinib (n=60) and erlotinib (n=17), b)The regimens used after cessation of the initial EGFR-TKI (n=2); osimertinib (n=1) and erlotinib (n=1), c)The regimens used after cessation of the initial EGFR-TKI (n=15); afatinib (n=2), erlotinib (n=1), gefitinib (n=3), olmutinib (n=2), and osimertinib (n=7), d)The regimens used after cessation of the initial EGFR-TKI (n=6); pemetrexed/cisplatin (n=2), crizotinib (n=1), gemcitbaine/carboplatin (n=2), and vinorelbine (n=1).

• 

  Fig. 2 Representative cases of SSNs showing the response to EGFR-TKIs over time (A) and responding to the initial and subsequent EGFR-TKI therapies over time (B). (A) The primary tumor was positive for the EGFR L858R mutation. A pure ground-glass nodule in the right upper lobe decreased markedly in size after initiating gefitinib. (B) The primary tumor was positive for the EGFR exon 19 deletion. A part-solid nodule in the left upper lobe decreased markedly in size after initiating gefitinib. The size of the nodule increased after stopping gefitinib and initiating gemcitabine. However, the size of nodule decreased again after initiating erlotinib. EGFR, epidermal growth factor receptor; SSN, subsolid nodule; TKI, tyrosine kinase inhibitor.

Reference

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