Advances in postoperative adjuvant targeted therapy for patients with stage ⅠB-ⅢA non-small cell lung cancer

doi:10.3969/j.issn.1674-8115.2022.11.014

Abstract

Abstract:

As the cancer with the highest mortality rate in the world, the treatment of lung cancer has always been a difficult problem for a wide range of patients and physicians alike. Based on the degree of differentiation, morphological features and biological characteristics, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). The incidence of NSCLC accounts for 80%?85%. Clinically, the treatment options of NSCLC include surgery, chemotherapy, radiotherapy, targeted drug therapy, immunotherapy, etc. For the patients with stage ⅠB?ⅢA NSCLC, in addition to the first choice of surgical treatment, postoperative adjuvant therapy is applied to reduce tumor recurrence and metastasis. Studies have shown that targeted drugs are efficient and safe in the adjuvant therapy for NSCLC patients, and the most attention has been given to agents that target mutations in the epidermal growth factor receptor (EGFR) gene, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). At present, three generations of EGFR TKIs have been approved for clinical use. Among them, the first generation EGFR-TKIs are dominant in the research and application of adjuvant therapy. For example, erlotinib and gefitinib can prolong the disease-free survival (DFS) and overall survival (OS) of patients after surgery, and icotinib has been approved for postoperative adjuvant therapy in China because of its obvious improvement of patients' DFS. Compared with the placebo, the third generation EGFR-TKIs drug osimertinib demonstrated a more significant DFS advantage in the ADAURA trial, decreased tumor recurrence in central nervous system and brought greater benefits in DFS to patients previously treated with standard chemotherapy regime. Osimertinib or chemotherapy combined with osimertinib has therefore become the standard of care for the patients with postoperative adjuvant therapy of stage ⅠB?ⅢA NSCLC. As the third generation EGFR-TKIs new drugs, the clinical trials of almonertinib and furmonertinib for postoperative adjuvant therapy are also underway. This article systematically summarizes the structure of EGFR, the types and detection methods of EGFR gene mutations, introduces the treatment strategies of clinical use of EGFR-TKIs, and discusses the problems that may be encountered in the clinical use of EGFR-TKIs.

Key words: non-small cell lung cancer (NSCLC), targeted therapy, adjuvant therapy, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib

CLC Number:

R655.3

LI Ruonan, CHEN Xiaoke, XU Yuanyuan, TAN Qiang. Advances in postoperative adjuvant targeted therapy for patients with stage ⅠB-ⅢA non-small cell lung cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(11): 1612-1619.

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References 43

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Trial	Phase	Stage	Number of enrolled patient/n	Adjuvant regimen	EGFR-TKIs duration	Primary endpoint	DFS/month	OS/month
ADJUVANT^［18-19］	Ⅲ	Ⅱ‒ⅢA （N1‒N2）（7^th TNM）	222	Adjuvant gefitinib vs VP	2 years	Median DFS	30.8 vs 19.8， HR （95%CI）=0.51 （0.36‒0.72）	75.5 vs 62.8， HR （95%CI）=0.92 （0.62‒1.36）
IMPACT^［20］	Ⅲ	Ⅱ‒ⅢA （N1‒N2）（7^th TNM）	234	Adjuvant gefitinib vs VP	2 years	Median DFS	35.9 vs 25.0， HR （95%CI）=0.92 （0.67‒1.28）	NR vs NR， HR （95%CI）=1.03 （0.65‒1.65）
EVIDENCE^［21］	Ⅲ	Ⅱ‒ⅢA （7^th TNM）	322	Adjuvant icotinib vs VP or cis/pem	2 years	Median DFS	47.0 vs 22.1， HR （95%CI）=0.36 （0.24‒0.55）	NR vs NR， HR （95%CI）=0.91 （0.42‒1.94）
ADAURA^［22］	Ⅲ	ⅠB‒ⅢA （N1‒N2）（7^th TNM）	682	Adjuvant chemotherapy （optional） followed by osimertinib vs adjuvant chemotherapy followed by placebo	3 years	Median DFS Ⅱ‒ⅢA	NR vs 20.4， HR （95%CI）=0.17 （0.11‒0.26）	NR vs NR， HR （95%CI）=0.40 （0.18‒0.90）

Trial	Phase	Stage	Number of enrolled patient/n	Adjuvant regimen	EGFR-TKIs duration	Primary endpoint	DFS/month	OS/month
ADJUVANT^［18-19］	Ⅲ	Ⅱ‒ⅢA （N1‒N2）（7^th TNM）	222	Adjuvant gefitinib vs VP	2 years	Median DFS	30.8 vs 19.8， HR （95%CI）=0.51 （0.36‒0.72）	75.5 vs 62.8， HR （95%CI）=0.92 （0.62‒1.36）
IMPACT^［20］	Ⅲ	Ⅱ‒ⅢA （N1‒N2）（7^th TNM）	234	Adjuvant gefitinib vs VP	2 years	Median DFS	35.9 vs 25.0， HR （95%CI）=0.92 （0.67‒1.28）	NR vs NR， HR （95%CI）=1.03 （0.65‒1.65）
EVIDENCE^［21］	Ⅲ	Ⅱ‒ⅢA （7^th TNM）	322	Adjuvant icotinib vs VP or cis/pem	2 years	Median DFS	47.0 vs 22.1， HR （95%CI）=0.36 （0.24‒0.55）	NR vs NR， HR （95%CI）=0.91 （0.42‒1.94）
ADAURA^［22］	Ⅲ	ⅠB‒ⅢA （N1‒N2）（7^th TNM）	682	Adjuvant chemotherapy （optional） followed by osimertinib vs adjuvant chemotherapy followed by placebo	3 years	Median DFS Ⅱ‒ⅢA	NR vs 20.4， HR （95%CI）=0.17 （0.11‒0.26）	NR vs NR， HR （95%CI）=0.40 （0.18‒0.90）

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