Since the advent of targeted therapy, many patients with advanced lung cancer have achieved prolonged survival, and even some patients can survive with tumors for a long time, which is not uncommon for more than ten years. For EGFR gene mutations, the mutation rate of Asian non-smoking women has reached 60%, which is much higher than that of Caucasians in Europe and the United States, so some people say that targeted drugs are gifts to Asian lung cancer patients.
The most common types of EGFR mutations are exon 19 mutations and 21 exon L858R mutations, especially 19 exon mutations, known as "golden mutations", and lung cancer patients with such gene mutations are the preferred targeted therapy. Whether it is advanced lung cancer, or IB ~ III lung cancer postoperative patients, as long as there are the above two mutations, the third generation of targeted drugs oscitinib is preferred. Since the advent of the ADAURA study, adjuvant targeted therapies for lung cancer have been included in major guideline recommendations in 2021.
On March 5, 2022, the 19th China Lung Cancer Summit Forum was held in Guangzhou. In the expert consensus of the 19th China Lung Cancer Summit Forum, the following provisions are made for the selection of adjuvant targeted therapy for phase III NSCLC:
1. Routine detection of EGFR and PD-L1 status before phase III NSCLC treatment (degree of evidence: strong; degree of recommendation: strong);
2. Adjuvant chemotherapy after phase III complete resection of EGFR mutation is not necessary (degree of evidence: moderate; degree of recommendation: medium);
3. Both the first generation EGFR TKI and the third generation EGFR TKI can be used for postoperative adjuvant therapy, and osimertinib is preferred (degree of evidence: strong; degree of recommendation: strong);
4. In postoperative patients with stage III lung cancer with co-mutation of RB1 and EGFR, adjuvant chemotherapy is preferred (degree of evidence: medium; degree of recommendation: medium).
From point 2, patients with stage III lung cancer with EGFR mutations can only consider targeted therapy after surgery, rather than necessarily targeted therapy after chemotherapy. But we can see from point 4 that if there is a co-mutation in RB1 and EGFR, targeted therapy is not recommended, and adjuvant chemotherapy should be prioritized instead. Why is that?
Although a large proportion of lung cancer patients have EGFR mutations, many patients not only carry EGFR mutations, but also mutations in other genes, also known as co-mutations. The mutations that occur with EGFR mutations in lung adenocarcinoma are mainly TP53, RB1, CTNNB1, and PIK3CA.
In 9.5-10.3% of lung adenocarcinomas with EGFR mutations, the inactivated mutation of RB1 is a clonal and early genetic event. Most RB1 mutations are accompanied by TP53 mutations, which are closely related to the regulation of the cell cycle. In EGFR mutated lung adenocarcinoma, patients with co-mutations of TP53 and RB1 have poor EGFR TKI therapy, and lung adenocarcinoma is prone to transformation into small cell carcinoma after drug resistance. RB1 mutations are associated with a poor prognosis.
According to the results of the biomarker study of CTONG1104 by the team of well-known domestic expert Professor Wu Yilong, EGFR-TKI is less effective and more suitable for chemotherapy in patients with EGFR-TKI with RB1 and TP53 co-mutations. 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 after surgery rather than targeted therapy.