Drug therapy for lung cancer includes chemotherapy, molecular targeted therapy and immunotherapy. Chemotherapy is divided into neoadjuvant chemotherapy, adjuvant chemotherapy and palliative chemotherapy, which should be administered under the guidance of medical oncologists and with strict clinical indications. Chemotherapy should be administered under the guidance of medical oncologists, taking into account the patient’s disease stage, physical condition, adverse effects, quality of life and patient’s wishes, and avoiding over- or under-treatment. The efficacy of chemotherapy should be evaluated in a timely manner, adverse effects should be closely monitored and prevented, and drugs and/or doses should be adjusted as appropriate. Molecularly targeted therapy requires the identification of gene mutation status and guidance of targeted therapy based on molecular typing. In recent years, immunotherapy represented by immune checkpoint inhibitors (such as PD-1 monoclonal antibody or PD-L1 monoclonal antibody) has been shown to improve the survival rate of lung cancer patients. Several PD-1 monoclonal antibodies and/or PD-L1 monoclonal antibodies have been approved and marketed for the treatment of advanced and locally advanced NSCLC and SCLC, and more clinical indications are still being explored.

Pharmacological treatment of advanced NSCLC

(1) First-line drug therapy: For patients with negative driver genes, a platinum-containing two-drug regimen is the standard first-line chemotherapy regimen, and for patients with nonsquamous carcinoma, a combination of antivascular therapy, such as bevacizumab or vascular endothelial inhibitory protein, can be used on top of chemotherapy. A two-drug platinum-containing chemotherapy based on karilizumab, pablizumab, tirelizumab, sindilizumab or atelelizumab in combination with pemetrexed is recommended. For squamous carcinoma, pablizumab, tirelizumab in combination with paclitaxel or sindilizumab in combination with gemcitabine platinum-containing two-drug chemotherapy is recommended. If patients are PD-L1 positive (TPS ≥ 1), pabrolizumab monotherapy is feasible, where the benefit of immunotherapy is more pronounced in patients with high PD-L1 expression (TPS ≥ 50). Patients with high PD-L1 expression (TC ≥ 50 or IC ≥ 10) may also receive atelelizumab monotherapy. For patients with positive driver genes, such as EGFR mutations
(including exon 19 deletions, exons 21 L858R and L861Q, exon 18 G719X, and exon 20 S768I), epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is an option for patients with positive driver genes. These include gefitinib, erlotinib, erlotinib, daclotinib, afatinib, or oseltinib. Patients with a positive ALK fusion gene may be treated with alectinib, ceritinib, or crizotinib, and patients with a positive ROS1 fusion gene may be treated with crizotinib. For patients with C-met14 jump mutation who are intolerant to chemotherapy, sevotinib is an option. The currently available therapeutic options are detailed in Tables 2 and 3.
Table 2 Common first-line chemotherapy and chemotherapy-combined immunotherapy regimens for non-small cell lung cancerTable 3 Commonly used antivascular, immunotherapy, and targeted therapy agents for non-small cell lung cancer
Maintenance therapy is an option for patients who achieve disease control (complete remission, partial remission, or stable) after first-line therapy. Current agents with evidence-based evidence for same-drug maintenance therapy include pemetrexed (nonsquamous), bevacizumab (nonsquamous), and gemcitabine, with a recommended 2-year cycle for immune checkpoint inhibitors in the absence of disease progression and intolerable adverse events; agents with evidence-based evidence for switch maintenance therapy include pemetrexed (nonsquamous), and for EGFR gene-sensitive mutations Patients with EGFR-sensitive mutations can choose EGFR-TKI for maintenance therapy.
(2) Second-line drug therapy: chemotherapeutic agents including docetaxel and pemetrexed are available; molecular targeting agents for patients with EGFR mutation, ALK fusion or ROS1 fusion are available; immunotherapy including nabumetinumab is available.
For patients with positive driver mutations, second-line therapy should be prioritized with molecularly targeted agents if the corresponding molecularly targeted agents are not used in first-line and maintenance therapy; for patients who are resistant to first-line EGFR-TKIs and positive for EGFR T790M mutations, second-line therapy should be prioritized with third-generation EGFR-TKI, such as oseltinib, ametinib or vomitinib. For ALK fusion-positive patients who develop resistance after first-line treatment with crizotinib, ceritinib or aletinib may be chosen for second-line treatment. In case of oligogenic or CNS progression after resistance to first-line molecular targeted therapy, the combination of targeted therapy with local therapy, such as radiotherapy or surgery, may be continued. For patients with resistance to first-line EGFR-TKI or ALK inhibitors, second-line treatment may also be based on the Eastern Cooperative Oncology Group performance status (ECOG PS) for two platinum-containing agents or single-agent chemotherapy regimens for non-squamous cancers. In the case of non-squamous carcinoma, an anti-vascular agent such as bevacizumab may be added to this regimen.
For patients with driver-negative disease, chemotherapy should be given priority, and for patients without driver genes and with squamous histology, afatinib is an option (Table 3).
(Table 3).
Immune checkpoint inhibitors may be an option for patients with NSCLC after failure of platinum-containing two-drug combination chemotherapy/targeted therapy.
(3) Third-line drug therapy: Third-line therapy is also available in clinical trials as a single oral VEGF receptor tyrosine kinase inhibitor or, if an immune checkpoint inhibitor is not used in the first or second line, navulizumab may be considered. The current evidence-based third-line treatment with VEGF receptor tyrosine kinase inhibitors is supported by anlotinib.
(4) Locally advanced or metastatic NSCLC with MET exon 14 jump mutations that have progressed after chemotherapy or are intolerant to standard platinum-containing chemotherapy may be treated with sevotinib; locally advanced or metastatic NSCLC with RET gene fusions that have previously received platinum-containing chemotherapy may be treated with pratinib. For other driver mutations, such as BRAF V600E mutation, NTRK fusion and other mutations, some new targeted drugs have achieved better efficacy in clinical trials, so patients with rare mutations are encouraged to participate in the corresponding clinical trials and can be considered for treatment with the corresponding drugs in appropriate clinical situations.
Table 4 Common second-line treatment options for non-small cell lung cancer

Drug therapy for non-surgically resectable NSCLC

Principles of chemotherapy for lung cancer(1) Patients with lung cancer with KPS <60 or ECOG >2 should not be treated with chemotherapy, which can be relaxed for SCLC patients.
(2) Patients with lung cancer with white blood cells <3.0×109/L, neutrophils <1.5×109/L, platelets <100×109/L, red blood cells <2×1012/L, and hemoglobin <80g/L should not be treated with chemotherapy in principle.
(3) In principle, chemotherapy is not recommended for patients with severe liver and kidney function abnormalities, and/or severe abnormal laboratory indicators, or those with severe complications, infections, fever, or bleeding tendencies.
(4) If the following conditions occur during chemotherapy, discontinuation or change of regimen should be considered: if the lesion progresses after 2 weeks of treatment or deteriorates again during the rest period of the chemotherapy cycle, the original regimen should be discontinued and other regimens should be used as appropriate; if the adverse reaction of chemotherapy reaches grade 3-4 and poses a significant threat to the patient’s life, the drug should be discontinued and the treatment regimen should be adjusted at the next treatment; if serious complications occur, the drug should be discontinued and the treatment regimen should be adjusted at the next treatment. If serious complications occur, the drug should be discontinued and the treatment plan should be adjusted during the next treatment.
(5) The standardization and individualization of the treatment plan must be emphasized. The basic requirements of chemotherapy must be mastered. In addition to the routine application of antiemetic drugs, platinum drugs other than carboplatin need to be hydrated and diuretic. Close monitoring of routine blood and biochemical indicators after chemotherapy.
The efficacy evaluation of chemotherapy is based on the RECIST efficacy evaluation criteria.