EGFR gene mutations are the most common driver gene mutation in lung adenocarcinoma, and about 50% of patients with lung adenocarcinoma have EGFR gene sensitive mutations. At present, there are many targeted drugs to choose from for EGFR gene mutations. Targeted drugs are easy to

EGFR gene mutation is the most common driver gene mutation in lung adenocarcinoma . About 50% of lung adenocarcinoma patients have EGFR gene sensitive mutations. At present, there are many targeted drugs to choose from for EGFR gene mutations. Targeted drugs are easy to use and have few side effects. Their excellent efficacy has improved the survival and quality of life of many patients.

However, drug resistance always occurs. Once drug resistance is resistant, the condition will progress rapidly, making the patient's physical condition worse and worse. If there is no better treatment measure after drug resistance, the patient has no choice but to choose chemotherapy, but it often makes the patient's physical condition worse. The fundamental reason for this result in

is that different drug resistance mechanisms determine different treatment strategies. Therefore, we need to understand the specific causes of drug resistance very accurately and find the right therapeutic drugs.

subtype transformation of lung cancer: the most difficult mechanism of drug resistance

It is reported that 3%-14% of lung adenocarcinomas will undergo transformation to small cell lung cancer during targeted treatment. If the patient has inactivated mutations in the RB1 gene and TP53 gene, it is more likely to transform into small cell lung cancer. Once subtype transformation occurs, the patient becomes transformed small cell lung cancer (T-SCLC), which is usually manifested as resistance to EGFR-targeted drugs, and the patient's prognosis is also relatively poor.

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Currently, the standard treatment for small cell lung cancer is to use etoposide combined with platinum chemotherapy. This treatment regimen is generally used when patients with lung adenocarcinoma are resistant to targeted drugs and convert to small-cell lung cancer. However, the benefit was not good. Although 54% of patients had a treatment response, the median progression-free survival time was only 3.4 months.

PD-L1 inhibitor has been used in the treatment of small cell lung cancer. Therefore, the researchers launched a study to study the therapeutic effect of immunotherapy on this lung cancer subtype by analyzing the characteristics of transformed small cell lung cancer patients using immunotherapy for .

treatment is effective. Pay attention to identifying the drug combination

. A total of 47 patients were admitted to this clinical trial. All of these patients have EGFR gene mutations, all of which are transformed small cell lung cancer (T-SCLC), and have received targeted drug treatment. Eleven of the patients used immunotherapy (I/O group) in subsequent treatment, while the remaining 36 patients did not use immunotherapy (non-I/O group).

1 patients who used immunotherapy, 9 patients were given the PD-L1 inhibitors atelizumab, bevacizumab , carboplatin and albumin-binding paclitaxel. The other two patients were treated with atelizumab, etoposide and carboplatin. In 11 patients who used immunotherapy, the overall treatment response rate was 73%, and 8 patients had therapeutic effects.

Compared with patients who did not use immunotherapy, patients who used PD-L1 inhibitor immunotherapy, the progression-free survival time was extended from 4.1 months to 5.1 months, an extension of 1 month. The overall survival was largely different. The median overall survival of the I/O group using immunotherapy was 20.2 months, and the median overall survival of the non-I/O group without immunotherapy was 7.9 months.

In addition, researchers found that mutations in EGFR affect progression-free survival. If the patient has a L858R point mutation in the EGFR gene, the progression-free survival is significantly longer than the 19del mutation in the EGFR gene. If the patient's PD-L1 expression was positive, the median progression-free survival was 6 months, and if the patient's PD-L1 expression was negative, the median progression-free survival was 3.7 months.

concluded that if lung adenocarcinoma is converted into small cell lung cancer, using the PD-L1 inhibitor atetirizumab, combined with bevacizumab, carboplatin and other drugs is an effective treatment strategy.

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enlightenment

Summary of the above content, there are the following enlightenment:

1. Transformed small cell lung cancer is a relatively special subtype of lung cancer with a poor prognosis.After the patient uses targeted drugs to resist drugs, it is recommended to extract the newly-occurred lesion sample and biopsy for pathological typing. If a situation is transformed into small cell lung cancer, the use of chemotherapy drugs for lung adenocarcinoma is ineffective.
2. If transformed small cell lung cancer occurs, the main treatment method is the combination of PD-L1 inhibitors, chemotherapy and bevacizumab. Bevacizumab is often not available in small cell lung cancer medication regimens. This study tells us that bevacizumab can be used.
3. gene test when necessary to clarify the specific drug resistance mechanism, so that subsequent treatment plans can be determined.

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References:

C-Y. Zhang, et al., A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival, Lung Cancer (2022)