Resistant to lung cancer targeted drugs? Don't worry, here's a solution!

Ms. Liu was diagnosed with lung cancer in 2020 and underwent a 3D thoracoscopic lobectomy (right upper lobe) + thoracoscopic mediastinal lymph node dissection under general anesthesia. Postoperative pathology revealed: (right upper lobe) invasive adenocarcinoma, with a maximum tumor diameter of 6cm, satellite foci around the tumor, involvement of the bronchial wall and pleura, visible airway dissemination, and positivity in the fourth group of lymph nodes. Genetic testing revealed: CTNNB1 mutation type SNV exon 3 mutation site G34A, mutation frequency 47.11%; EGFR mutation type InDel exon 19 mutation site E746-A750del, mutation frequency 30.46%.

The patient was found to have EGFR mutations and started taking erlotinib treatment. In November of the same year, due to intolerance, she switched to taking Icotinib. In September 2021, a follow-up lung CT scan revealed two small nodules in the upper segment of the right lower lobe, suggesting metastatic disease. Considering that the original targeted drug had developed resistance, she switched to taking Amatinib and has been on it ever since.

Based on Ms. Liu's case, let's explore the solutions to targeted drug resistance.

The medication time is determined through extensive clinical trials. Some drugs are taken on an empty stomach, while others are taken half an hour after a meal. This is due to pharmacokinetics, which requires maintaining a stable blood drug concentration. Therefore, it is essential to strictly follow the instructions and avoid discontinuing medication, as this can delay the emergence of drug resistance in targeted drugs.

The differences between the three generations of targeted drugs: The first and second generation targeted drugs are classified based on the strength of their binding to the target and whether it is reversible; while the third generation targeted drugs are specifically developed for specific gene mutations (T790M) that occur after resistance to the first or second generation drugs. Theoretically, each generation is "stronger than the previous one." Patients undergoing targeted therapy usually start with the first generation of targeted drugs. If the first generation fails, the second or third generation can be used, and often shows some effect. The targeted drugs that Ms. Liu first used, Icotinib and Icotinib, are first-generation targeted drugs, while the later-replaced Amatinib belongs to the third-generation targeted drugs.

Some research data have found that combining targeted therapy with chemotherapy, radiotherapy, immunotherapy, etc. can achieve synergistic anti-cancer effects, not only improving treatment outcomes but also delaying the occurrence of drug resistance.

Ms. Liu took corresponding targeted drugs for treatment after surgery, but new lesions still appeared in the second year and were considered to be possibly metastatic. She was concerned that the targeted drugs were difficult to suppress the tumor, and had already switched to third-generation targeted drugs. If drug resistance occurred again, the choices of drugs would become increasingly limited. After contacting Professor Zhang Minghui's team, the Lehe New Medical team provided a comprehensive evaluation and second diagnosis and treatment suggestion:

1. Ms. Liu's tumor was large at the time of diagnosis, with a maximum diameter of 6cm and late-stage lymph node metastasis.

2. Pathological findings revealed tumor involvement of the bronchial wall and pleura, as well as intrapulmonary dissemination, which greatly increased the probability of future recurrence and metastasis.

3. The patient was found to have gene mutations and was treated with targeted drugs, but new lesions still appeared in the second year, suggesting resistance to the original targeted drugs. The patient was switched to Amatinib.

4. Combining targeted drugs with vNKT cell therapy can prolong the time before targeted drug resistance occurs, eliminate residual cancer cells in the body, and prevent recurrence and metastasis.

Ms. Liu began using vNKT cell therapy in March 2022 and has completed a total of 25 courses of cell therapy so far. During this period, she continued to use the targeted drug Amatinib for 3 years without experiencing drug resistance, achieving long-term stable efficacy. The treatment is still ongoing.