Lung cancer is one of the most common malignant tumors in the world, and the latest statistics show that there are more than 800,000 new cases of lung cancer in mainland China, which has become the first cause of malignant tumor death in the urban population of mainland China. Non-small cell lung cancers account for about 80% of all lung cancers, about 30% have reached stage III at the time of presentation, and most have lost the best time for surgical treatment. The current treatment plan is gradually transitioning from synchronous radiotherapy and chemotherapy to immunotherapy, targeted therapy and other methods.
Mutation in the EGFR gene in patients with non-small cell lung cancer
Studies have shown that lung cancer is caused by multi-gene involvement, including the activation of oncogenes, the inactivation of tumor suppressor genes, and miRNA alterations. Non-small cell lung non-squamous cell carcinoma (adenocarcinoma), mainly including EGFR, ALK, ROS1, MET and other mutations, in the known variety of NSCLC driver gene mutations, EGFR mutation is the most important type of mutation, especially in Asian non-smoking women EGFR mutation rate of 60%. Therefore, EGFR mutations have become a key target for targeted therapy in patients with non-scaly non-small cell lung cancer, and further studies have shown that exon 19 deletion and 21st exon L858R mutations are the most common types in East Asian populations. Patients with such gene mutations can benefit from corresponding targeted drugs, and the use of three generations of EGFR-TKI targeted drugs such as osetinib and ametinib is currently recommended in China. The "19th China Lung Cancer Summit Forum" that ended in March this year has a new consensus on adjuvant targeted therapy for patients with stage III non-small cell lung cancer mutations.
Chinese experts agree on adjuvant targeted therapy for stage III non-small cell lung cancer
The 19th China Lung Cancer Summit Forum reached a six-point consensus on the choice of adjuvant targeted therapy for stage III non-small cell lung cancer (see table below):
Note: Drugs for EGFR exon 19 deletion and exon 21 L858R mutations
Generation of targeted drugs: gefitinib, erlotinib, extinib
Three generations of targeted drugs: osimettinib, ametinib, voltemitenib
The second point of this year's expert consensus (the dark part in the figure above) has strong clinical guidance:
It is clear that patients must have EGFR and PD-L1 tests before treatment, which can be a good guide to targeted therapy or the use of PD-1 immune checkpoint inhibitor drugs; avoid inappropriate treatments.
The regimen recommended in previous guidelines has been changed to not necessarily use chemotherapy after surgery in patients with stage III non-small cell lung cancer with EGFR mutations, and can be treated with appropriate targeted drugs according to the patient's situation.
For EGFR-TKI first-generation gefitinib (class 1B evidence), exetinib (class 1B evidence) or erlotinib (class 2 evidence)] and third-generation osimtinib (class 1A evidence) that are also suitable for adjuvant therapy, it is more recommended to give priority to osiminib (or a third-generation drug of the same class).
More critically, also based on the results of genetic testing, if there are co-mutant RB1 and EGFR mutations, adjuvant targeted therapy is not recommended, and adjuvant chemotherapy is recommended.
What other mutations coexist with EGFR that are not suitable for targeted therapy?
Lung cancer is often not caused by a single mutation, and patients also carry other mutations, such as TP53, RB1, PTEN, MDM2, CTNNB1, PIK3CA and so on. There are currently no suitable targeted drugs for such mutations. Some studies have found that when EGFR mutations coexist with these mutations, the time to benefit patients from EGFT-TKI-targeted drugs is shortened. The following are the cases where EGFR mutations coexist with TP53, RB1, PTEN, and MDM2 mutations, respectively, and patients are treated with EGFR-TKI targeted drugs, and patients will develop drug resistance problems in a short period of time.
Even if there are three mutations of EGFR +TP53 + RB1 at the same time, the probability of such patients turning into small cell lung cancer is 18%.
What should I do if I have EGFR co-mutation or stage III non-small cell lung cancer with a negative EGFR mutation?
According to the results of the biomarker study of CTONG1104 in China, EGFR-TKI is less effective and more suitable for chemotherapy in patients with EGFR-positive mutations of RB1 and TP53.
For some non-inoperable patients with stage III non-small cell lung cancer with a negative EGFR mutation, immuno-booster therapy is recommended after synchronized chemoradiotherapy, while after sequential chemoradimab, only sugemalimab is recommended for immunotrophic therapy.
Write at the end
As the first PD-L1 drug to enter the mainland, duvalliumab was approved for use in patients with stage III non-small cell lung cancer that cannot be surgically removed. At present, the drug has not entered the 2022 national drug collection list.
Author | U.S.-China Jia and Cancer Prevention
Article Review | Director of Department of Oncology, Guangzhou Taihe Cancer Hospital, Liu Huixia
Director kang Shijun, Department of Oncology, Guangzhou Taihe Cancer Hospital