EGFR-mutant non-small cell lung cancer patients harboring CDK4 amplification show favorable response to afatinib:Two case reports

To the Editor:Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)show significant efficacy in patients with advanced-stage non-small cell lung cancer(NSCLC)with sensitive EGFR mutations and significantly prolong the survival of these patients.However,drug resistance emerges in most patients.Previous studies indicated that cyclin-dependent kinase 4/6(CDK4/6)gene amplification was one of the resistance mechanisms of the EGFR-TKI osimertinib,weakening its efficacy.Treatment options for EGFR-mutant NSCLC patients with CDK4 amplification are limited to add CDK4 inhibitors.

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

Asian,regional,and national burdens of respiratory tract cancers and associated risk factors from 1990 to 2019:A systematic analysis for the global burden of disease study 2019

Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and West.This study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national levels.Methods:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 database.Age-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian countries.Results:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer increased.Smoking was the leading specific risk factor for deaths from both TBL and larynx cancers.The burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central Asia.Deaths,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent years.Conclusions:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in Asia.SDI and smoking were the main factors influencing the disease burden of TBL cancer in Asian countries.This study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.