Lung cancer is one of the most common malignant tumors in the world and has become the first cause of death from malignant tumors in China’s urban population.
Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers, and the incidence of NSCLC in China is 39/100,000, with a slightly higher incidence in men than in women.
The median survival time for NSCLC is 22.7 months, the overall survival rate at 1 year is 71.8%, the 5-year survival rate is about 15%, and about 70% of NSCLC patients are diagnosed at advanced stage.
In this article, we run through the key points of NSCLC treatment.
Tumor Markers(TM) of Lung Cancer
Serum tumor markers related to lung cancer: carcinoembryonic antigen (CEA), CA125, CA153, cytokeratin fragment 19 (CYFRA21-1), squamous epithelial cell carcinoma antigen (SCCA)
Small cell lung cancer: precursor of gastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), creatine kinase BB (CK-BB), chromoprotein
A (CgA), which can detect the efficacy and recurrence.
Immunohistochemical markers to differentiate adenocarcinoma from squamous carcinoma: TTF-1, Napsin-A, p63, P40, CK5/CK6
Imaging tests
Gene mutation detection
Specimens: surgically excised and biopsied tissue (preferred), circulating tumor DNA (DNA, ctDNA ) or blood (plasma) specimens ctDNA
ALK fusion gene testing: lung adenocarcinoma, NSCLC patients with adenocarcinoma components and adenocarcinoma differentiation
EGFR-sensitive gene testing: lung adenocarcinoma, NSCLC with adenocarcinoma component, adenocarcinoma differentiation, non-smoking patients with squamous carcinoma
EGFR-TKI treatment failure detection: Tumor tissue biopsy can be taken again to clarify the lesion tissue type, and if it is NSCLC, T790M mutation, MET gene amplification, HER2
gene amplification, PIK3CA mutation, BRAF gene V600E mutation, ERK amplification, etc.
Click here to view: All in one: 28 targeted drug uses and adverse effects in 7 cancers
EGFR(-) and ALK(-), mutation status unknown
1. first-line therapy
Eastern U.S. Oncology Collaborative Group Physical Status (PS) score
≥ 3 points: chemotherapy not recommended, best supportive care feasible
2 points: single agent chemotherapy
0 to 1: Two-drug platinum-containing chemotherapy ± anti-VGFR
Cisplatin / carboplatin ➕ pemetrexed (for non-squamous NSCLC) / gemcitabine / docetaxel / paclitaxel ± bevacizumab / vincristine ± Endo / S-1
Cannot tolerate platinum with non-platinum-containing two-drug chemotherapy.
Maintenance therapy after first-line therapy
Co-drug maintenance: pemetrexed (for non-squamous NSCLC), gemcitabine
Switching maintenance: pemetrexed (for non-squamous NSCLC), docetaxel
2. second-line treatment docetaxel, pemetrexed (for non-squamous NSCLC)
3. Third-line treatment clinical trials, best supportive care
ALK(+) Positive rate of ALK fusion gene in Chinese NSCLC patients is 3% to 11%.
ALK-TKI therapy: crizotinib
Post-resistance therapy: ceritinib, Alectinib
EGFR-TKI therapy for EGFR(+)
The rate of EGFR gene mutation in lung adenocarcinoma patients in China is 50.2%.
There are 4 types of EGFR gene sensitive mutations: exon 19 deletion mutation (19del), exon 21 point mutation, exon 18 point mutation, exon 20 insertion mutation (BIM), and exon 21 point mutation.
insertional mutations (BIM).
First-line treatment: gefitinib, erlotinib, afatinib, erlotinib;
EGFR-TKI maintenance is an option for non-progression (CR, PR, SD) after first-line chemotherapy.
Second-line therapy: EGFR-TK not applied at first-line and maintenance therapy; second-line preferred
Third-line therapy: EGFR-TKI, clinical trials
Treatment after drug resistance
Figure .Clinical management strategies after EGFR TKI resistance (according to Yang JJ et al. “Lung Cancer.
2013;79(1):33-9.”)
T790M point mutations (50% of cases): AZD9291
MET gene amplification, PI3K gene mutation, EGFR gene amplification: under study
Click here to view: Quick start guide: consensus on the management of resistance to small molecule targeted drugs in NSCLC
Immunotherapy with Nivolumab: Advanced squamous lung cancer that has failed previous therapy
Pembrolizumab: PD-L1 protein positive advanced NSCLC with prior treatment failure