Lung cancer is one of the most common malignant tumors in the world, and the mortality rate also ranks first among cancers, among which non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer, and most of them are already in advanced stage when they are diagnosed. In recent years, although the status of chemotherapy in the treatment of NSCLC has not been fundamentally shaken, its efficacy has reached a plateau, and toxicity and adverse effects have limited clinical application. Targeted therapy has become one of the most popular and promising treatments due to its reliable efficacy and mild toxicity and adverse effects.
The Lung Cancer Group of the Chinese Medical Association Respiratory Disease Branch and the China Lung Cancer Prevention and Treatment Alliance have organized relevant experts to discuss issues related to molecular targeted therapy for advanced NSCLC and formed an expert consensus on molecular targeted therapy for advanced NSCLC (2013 version), which is suitable for China’s national conditions. This paper summarizes the important conclusion part of it.
1.Driver gene testing
Recommendation.
NSCLC patients should try to obtain specimens for EGFR gene mutation testing before treatment;
EGFR test specimens need to be quality-controlled by pathologists and the appropriate test method should be selected for the test; a highly sensitive test method, such as the ARMS method, is recommended;
For patients without EGFR mutations, ALK and ROS-1 fusion gene testing is recommended;
It is recommended that EGFR gene mutation, ALK and ROS-1 fusion gene testing be performed simultaneously in units that have the conditions.
2. EGFR-TKI
2.1. First-line therapy
Recommendation.
For patients with advanced NSCLC with EGFR gene-sensitive mutations, EGFR-TKI is recommended for first-line use (many countries have approved gefitinib and erlotinib as first-line therapeutic agents, but only gefitinib has been approved in China, and afatinib has been approved as first-line therapeutic agents in the United States and Taiwan);
For patients with advanced NSCLC with EGFR gene-sensitive mutations, first-line chemotherapy combined with intercalated erlotinib for 6 cycles followed by maintenance therapy with erlotinib may be considered. 2.2. Maintenance therapy
Recommendation.
For patients with advanced NSCLC with disease control (PR/CR/SD) obtained with first-line chemotherapy, gefitinib or erlotinib maintenance therapy may be considered.
2.3. Second-line and follow-up therapy
Recommendation.
EGFR-TKI (gefitinib, erlotinib or erlotinib) can be used for second- or third-line treatment in patients with advanced NSCLC, while EGFR-TKI is recommended in preference for patients with EGFR-sensitive mutations;
Patients with EGFR wild-type are not recommended for second-line treatment with EGFR-TKI in preference.
2.4. Treatment of elderly patients and patients with low functional status scores
Elderly (over 70 years of age) lung cancer patients often have difficulty receiving platinum-containing two-drug chemotherapy due to poor organ function and comorbidities, while EGFR-TKI may be considered for first-line use because it is well tolerated.
Recommendation.
EGFR-TKI (gefitinib or erlotinib) therapy is recommended for elderly patients with EGFR-sensitive mutations;
For elderly or NSCLC patients who cannot tolerate chemotherapy and whose EGFR mutation status is unknown, EGFR-TKI (gefitinib or erlotinib) treatment can be tried due to the high EGFR gene mutation rate in Chinese patients and the absence of other effective treatment modalities, and the efficacy and toxicity and adverse effects should be closely observed.
2.5. Treatment after EGFR-TKI resistance
NSCLC patients with EGFR gene-sensitive mutations treated with EGFR-TKI in the first line usually experience disease progression after 9-10 months, suggesting the development of secondary EGFR-TKI resistance. A retrospective study enrolled 227 patients with secondary resistance and explored treatment patterns following disease progression on EGFR-TKI therapy.
Recommendation.
For patients with slow progression, continuation of the original EGFR-TKI therapy or EGFR-TKI in combination with chemotherapy is recommended;
For patients with rapid progression, it is recommended to discontinue EGFR-TKI and switch to chemotherapy;
In patients with local progression and well-controlled original lesions, it is recommended to continue EGFR-TKI and combine with local therapy.
3.ALK and ROS-1 fusion gene inhibitors
Recommendation.
For patients with advanced NSCLC positive for ALK and ROS-1 fusion genes, crizotinib is recommended for treatment.
4. Angiogenesis inhibitors
Bevacizumab is not recommended for the following conditions.
Squamous or mixed type of lung cancer with predominantly squamous carcinoma;
Tumor invasion of large blood vessels;
History of hemoptysis (1 hemoptysis >2.5ml);
Uncontrollable cardiovascular disease such as primary hypertension.
Recommendations.
For patients with advanced non-squamous NSCLC with a functional status score of 0 to 1, in the absence of significant hemoptysis and tumor invasion of large vessels, combining bevacizumab with first-line chemotherapy (carboplatin/paclitaxel or cisplatin/gemcitabine) is recommended (bevacizumab has no indication for lung cancer in China at this time, but is expected to be approved by CFDA soon);
For patients with advanced NSCLC, vincristine/cis-molybdenum in combination with recombinant human vascular endothelial inhibitor can be used.