Since the advent of targeted therapy, many patients with advanced lung cancer have been able to prolong their survival, and even some patients can live with the tumor for a long time. It is not uncommon for them to survive for more than ten years. For EGFR gene mutations, the mutation rate of Asian non-smoking women reaches 60%, which is much higher than that of white Europeans and Americans. Therefore, some people say that targeted drugs are gifts for Asian lung cancer patients.
The most common types of EGFR mutations are exon 19 mutation and exon 21 L858R mutation, especially exon 19 mutation, known as “golden mutation”. Targeted therapy is the first choice for lung cancer patients. Whether it is advanced lung cancer or postoperative patients with stage IB to III lung cancer, as long as there are the above two mutations, the third-generation targeted drug osimertinib is preferred. Since the advent of the ADAURA study, adjuvant targeted therapy for lung cancer has been included in major guideline recommendations in 2021.
On March 5, 2022, the 19th China Lung Cancer Summit Forum was grandly held in Guangzhou. In the expert consensus of the “19th China Lung Cancer Summit Forum”, adjuvant targeting for stage III NSCLC The choice of treatment is defined as follows:
1. Routine detection of EGFR and PD-L1 status before treatment in stage III NSCLC (evidence level: strong; recommendation level: strong);
2. Adjuvant chemotherapy after complete resection of stage III NSCLC with EGFR mutation is not necessary (level of evidence: moderate; level of recommendation: moderate);
3. Both first-generation EGFR TKI and third-generation EGFR TKI osimertinib can be used for postoperative adjuvant therapy, and osimertinib is preferred (evidence level: strong; recommendation level: strong) ;
4. For postoperative patients with stage III lung cancer with co-mutation of RB1 and EGFR, adjuvant chemotherapy is preferred (level of evidence: moderate; level of recommendation: moderate).
From the second point of view, patients with stage III lung cancer with EGFR mutation can only consider targeted therapy after surgery, not necessarily targeted therapy after chemotherapy. But we can find from point 4 that if there is co-mutation of RB1 and EGFR, targeted therapy is not recommended, and adjuvant chemotherapy should be given priority. Why is this happening?
Although a large proportion of lung cancer patients have EGFR mutations, many patients not only carry EGFR mutations, but also have mutations in other genes, also known as co-mutations. Mutations that co-occur with EGFR mutations in lung adenocarcinomas mainly include TP53, RB1, CTNNB1, and PIK3CA.
In 9.5-10.3% of EGFR-mutant lung adenocarcinomas, inactivating mutations in RB1 are clonal and early genetic events. Most RB1 mutations are accompanied by TP53 mutations, which are closely related to cell cycle regulation. In EGFR-mutated lung adenocarcinoma, patients with co-mutation of TP53 and RB1 have poor EGFR TKI treatment effect, and lung adenocarcinoma is easy to transform into small cell carcinoma after drug resistance. RB1 mutations are associated with poor prognosis.
According to the biomarker research results of CTONG1104 conducted by the team of well-known domestic expert Professor Wu Yilong, it is suggested that EGFR-positive patients with RB1 and TP53 co-mutation have poor efficacy with EGFR-TKI and are more suitable for chemotherapy . Therefore, for stage III lung cancer patients with a relatively high probability of recurrence and metastasis, even if there is an EGFR mutation, if there is a co-mutation of RB1, adjuvant chemotherapy is preferred over targeted therapy after surgery.