| Objective: summarize and analyze the baseline characteristics of EGFR co-mutation in patients with advanced NSCLC,tumor-related characteristics,genetic test results,and treatment efficacy,discuss and explore the clinical characteristics of EGFR co-mutation,and provide some evidence-based medical evidence for clinical understanding of EGFR co-mutation.Methods: From February 2008 to September2020 through the CAPTURE-Lung platform to collect and screen the general conditions and clinical data of patients with EGFR co-mutation advanced NSCLC,and use SPSS23.0 for statistical analysis of the following observation criteria: gender,age,tumor family History,smoking history,clinical characteristics: pathological type,clinical stage,physical fitness score,auxiliary examination,and therapeutic effect.Results:Among the 1396 patients with EGFR mutations in advanced NSCLC,the NGS detection rate was 31.09%(434/1396 cases)(≥58 genes),and the EGFR co-mutation rate was 14.86%(206/1396 cases).It was common in women and nonElderly,non-smokers,and no family history of tumors,compared with 1190 cases of EGFR single mutation(including compound mutation),there was no statistically significant difference in the above indicators.The tumor characteristics of patients with co-mutation of EGFR were mostly good with ECOG score,with a score of 0-2accounting for 75.73%(156/206 cases),adenocarcinoma,accounting for 79.81%(166/206 cases);stage IV mostly,accounting for 77.18%(159/206 cases);multi-site metastasis is prone to occur,with an incidence rate of 51.01%(101/206 cases);bone metastasis is the most common,accounting for 38.35%(79/206 cases),followed by brain metastasis accounting for 26.70%(55/206)Cases),the third is pleural metastasis,accounting for 22.82%(47/206 cases);and distant lymph node(N3)metastasis accounted for the least,13.60%(28/206 cases).The most common EGFR mutation subtype is EGFR21 exon L858 R point mutation,accounting for 43.69%(90/206cases),while the 19 exon deletion mutation is 38.34%(79/206 cases);the co-mutated gene is the driver gene accounting for 35.92%(74/206 cases)Including ALK,MET,ROS1,HER2,BRAF,RET,etc.;64.08%(132/206 cases)of co-mutation genes of unknown clinical significance,including: TP35,KRAS,PIK3 CA,RB1,PTEN,BIM,etc.EGFR co-mutation gene gene detection analysis showed that the most common incidence rate of TP53 was 33.98%(77/206 cases);the second was MET/c MET which accounted for 16.02%(33/206 cases),and the second incidence of ALK was13.11%(27/206).Among them,most of the co-mutated genes are single genes,accounting for 62.62%(129/206 cases),2 cases accounting for 21.36%(44/206),and≥3 cases accounting for 16.02%(33/206 cases).Treatment: 87.86% of all patients used EGFR-TKI as first-line treatment,and the highest rate of first-generation EGFR-TKI was 78.64%.Co-mutated genes are different,and EGFR-TKI has different efficacy.Among them,the co-mutated gene is ROS1,which has a better effect on EGFR-TKI.The PFS of the first generation EGFR-TKI can reach 21.8 months.The co-mutated genes are ALK,BRAF,and EGFR-TKI.The curative effect of EGFR is poor,and the PFS of the second-generation EGFR-TKI can be as high as 29.5 months for the co-mutated gene of HER2.HER2 co-mutation is equivalent to the sensitization gene of EGFR co-mutation to the second-generation EGFR-TKI;and the co-mutated gene is Patients with MET had a better effect on first-generation EGFR-TKI and PFS was 13.5 months;co-mutated genes were of unknown clinical significance.Among them,those with co-mutation gene TP53 had the worst effect on second-generation EGFR-TKI.PFS was 2.1 months,while first and third generations were used.The PFS of EGFR-TKI was 9.0 months and 14.4 months,respectively;the PFS of the first-generation EGFR-TKI was 10.0,12.2,and 10.3 months for the co-mutated genes KRAS,RB1,PIK3 CA,and the first-generation PTEN was used for the co-mutated genes The PFS of EGFR-TKI is 4.9 months.Conclusion: 1.The discovery of EGFR co-mutation benefited from the development and application of NGS detection technology.In this study,the NGS detection rate was 31.09%,and the incidence of EGFR co-mutation was 14.86%,suggesting that the potential incidence of EGFR co-mutation may be higher.2.Advanced NSCLC with co-mutation of EGFR is more likely to occur in non-elderly non-smokers,with good physical fitness scores and most of them without family history of tumors,more than 80% are adenocarcinoma and stage IV,and more than 50% have multiple distant metastases,which are prone to occur Bone metastasis,brain metastasis and pleural metastasis.3.There are 72 types of EGFR co-mutation genes in advanced NSCLC,and EGFR21 exon mutations are more prone to co-mutation.The proportion of co-mutated genes as driver genes is35.92%,which are more likely to accompany EGFR19 exons,and the rest are those with unclear clinical significance and are more closely related to EGFR L858 R.4.At present,the first-line treatment of EGFR co-mutation in advanced NSCLC is still based on EGFR-TKI.The first-line use rate of EGFR-TKI in this study is as high as87.86%.The efficacy of different TKIs is also different.Most co-mutated genes are driving genes.The curative effect of the patients is not good,but there are excellent curative data in the co-mutated genes ROS1 and HER2,which are worthy of in-depth study and verification.The efficacy of co-mutation genes of unknown significance is similar to that of EGFR single-gene mutations,but PTEN seems to be worse. |
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