Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Background and objective Epidermal growth factor receptor (EGFR) mutations occur more frequently in non-small cell lung cancer (NSCLC) of women, never smokers, Asian population and those with adenocarcinoma. Short in-frame deletion in exon 19 and L858R substitution are the most common mutations, which are closely associated with EGFR tyrosine kinase inhibitors (TKIs) treatment response. However, the therapeutic effects of EGFR-TKIs on NSCLC with uncom-monEGFR mutation subtypes remain unclear. hTe aim of this study is to investigate the clinicopathologic feature of uncom-monEGFR mutations and the outcomes of these patients.Methods Twenty-four patients that harbored uncommonEGFR mutations were included in this study. Clinicopathologic features of uncommonEGFR mutations and the outcomes of these patients were analyzed.Results Of the 24 patients, 13 received EGFR-TKIs treatment. hTe response rate of EGFR-TKIs treat-ment was 46.1%, and the median progression-free survival (PFS) was 7.4 months. Mutations on S768I and L861Q composed a major part (8 of 24) of uncommon mutations.Conclusions UncommonEGFR mutations constituted a unique part of the whole group ofEGFR mutations. hTeir composition and sensitivity to EGFR-TKIs were heterogeneous, which requires further assessment in a prospective study.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation.Limited to the standards of tumor tissue samples and detection methods,still some people can't receive target therapy following genetic guidance.This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation,who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital,analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.Results The objective response rate (ORR)was 52.8％ and the disease control rate (DCR) was 89.3％.The results showed that,patients with high CEA level before treatment responded better to TKIs (ORR 61.3％ vs 35.9％,DCR 95.2％ vs 74.4％,P＜0.001).Similar phenomena was found in patients with CEA decreased 1 month later (61.5％ vs 25％,P=0.002).Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo,P=0.027).To the opposite,PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo,P=0.029;9.0 mo vs 11.5 mo,P=0.023,respectively).Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1,normal baseline CYFRA21-1 and CEA decline predicted longer PFS.The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo,P=0.003;22.7 mo vs 55.0 mo,P＜0.001,respectively),while independent of CEA.Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma.While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.