What to do if targeted drug resistance occurs

Cancer is a dreadful topic. Many people are very afraid of it. It is also a difficult hurdle that is difficult to overcome with the current medical level, especially lung cancer. The incidence of lung cancer has shown an upward trend in my country, but the treatment method has not been very good. The early targeted drug treatment was effective, but drug resistance is very easy to occur. Once drug resistance occurs, there is no way to continue to achieve good results. What should we do if targeted drug resistance occurs?

The use of targeted drugs is one of the effective and safe methods for treating advanced lung cancer . However, we must clearly realize that targeted therapy cannot cure lung cancer. It is a palliative maintenance treatment, and it will fail like chemotherapy. Therefore, we have to face another thorny problem: what should we do after targeted therapy resistance?

Choose newer targeted drugs (such as AZD9291) or treat the disease according to the condition. For advanced non-small cell lung cancer with EGFR mutations, first-generation targeted drugs such as Iressa, Tarceva, and Conmana are often recommended for treatment. On average, patients will develop drug resistance in about one year. After developing drug resistance, we recommend that patients who are eligible actively undergo secondary genetic testing (puncture biopsy to obtain tumor tissue, or peripheral blood for ctDNA testing). Among them, approximately 50%-60% of patients will develop T790M mutation after developing drug resistance. For patients with better financial conditions, they can benefit from new T790M-specific targeted drugs, such as AZD9291. The remaining 40%-50% of patients can choose the standard platinum-containing two-drug combination regimen, which can also achieve certain therapeutic effects with tolerable side effects (for elderly and frail patients, single-drug chemotherapy such as pemetrexed can be considered).

Some friends with lung cancer chose chemotherapy at the beginning, but after a period of time, the chemotherapy failed. Clinicians will recommend first-generation targeted drugs such as Iressa, Tarceva, and Conmena as second-line options based on the patient's genetic mutation status. If the second-line targeted therapy fails again, such patients often face the difficult task of re-selecting a treatment plan: if the patient is in good general condition, chemotherapy or best supportive care is generally recommended clinically, usually with docetaxel, pemetrexed or a combination of platinum-containing chemotherapy, especially for patients who have been receiving targeted therapy for more than 6 months. There are also patients who have undergone repeated chemotherapy in the early stages, using different chemotherapy regimens in the first and second lines. As a result, the disease continued to progress, and targeted therapy was chosen for the third and fourth lines. Most of these patients cannot maintain this treatment for long. Targeted therapy failed, the patient's general condition score decreased, the condition became complicated, and the subsequent options available were extremely limited. For such patients, clinicians will readjust the treatment plan based on the patient's individual condition and the effectiveness of previous medications. For example, some patients fail targeted therapy and do not have T790M mutation. Most of these patients are caused by the activation of other pathways that promote cancer cell growth. For this type of patients, multi-target combination therapy can also be tried. This type of drug mainly includes sorafenib, sunitinib, vandetanib, etc. Relevant clinical research is currently being carried out at home and abroad, and the specific efficacy and side effects remain to be studied.

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