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Objective: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. Method: Hospital employees ≥40 years old who underwent low‐dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT‐imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation‐related occupation received monitoring in hospital. Result: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. Conclusion: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary. [ABSTRACT FROM AUTHOR]

Aim: Data for avelumab (anti-PD-L1 antibody) in Chinese patients are limited. Patients & methods: Phase I/Ib, open-label, dose-escalation study of Chinese patients with advanced solid tumors. Primary study objectives were to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of avelumab. Results: 24 patients received avelumab 3 mg/kg every 2 weeks (Q2W; n = 3), 10 mg/kg Q2W (n = 7), 20 mg/kg Q2W (n = 6) or 10 mg/kg weekly for 12 weeks and then Q2W thereafter (n = 8). MTD was not reached. Avelumab exposure was increased in higher dose groups. Partial responses occurred in two patients (confirmed in one patient); best overall response was stable disease in nine patients. Conclusion: Data for avelumab in Chinese patients with advanced solid tumors were consistent with previous global studies. [ABSTRACT FROM AUTHOR]

Background: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR‐sensitive mutations and de novo MET amplifications still need to be explored. Methods: A total of 54 patients from our hospital with non‐small cell lung cancer harboring EGFR‐sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan–Meier method with log‐rank statistics. Lung cancer organoids (LCOs) were generated from patient‐derived malignant pleural effusion to perform drug sensitivity assays. Results: Fifty‐four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp‐ (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp‐ and EGFR+/METamp + patients respectively, were as follows: the median progression‐free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post‐progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. Conclusion: EGFR+/METamp + patients treated with first‐line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first‐line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results. [ABSTRACT FROM AUTHOR]

In the global KEYNOTE‐042 study (Clinicaltrials.gov, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD‐L1)‐positive locally advanced/metastatic non–small‐cell lung cancer (NSCLC) without EGFR/ALK alterations. We present results from patients in KEYNOTE‐042 enrolled from China in the global or extension study (NCT03850444; protocol identical to global study). Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD‐L1 tumor proportion score [TPS] ≥50% vs 1%‐49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. Primary endpoints were OS in patients with PD‐L1 TPS ≥50%, ≥20% or ≥1%. Two hundred sixty‐two patients (pembrolizumab, n = 128; chemotherapy, n = 134) were enrolled from China. At data cutoff (February 21, 2020; median follow‐up, 33.0 [range, 25.6‐41.9] months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD‐L1 TPS ≥50% (hazard ratio [95% CI], 0.63 [0.43‐0.94]), TPS ≥20% (0.66 [0.47‐0.92]) and TPS ≥1% (0.67 [0.50‐0.89]). Grade 3 to 5 treatment‐related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months. Consistent with the global KEYNOTE‐042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD‐L1 TPS ≥1%, supporting first‐line pembrolizumab monotherapy for PD‐L1‐positive advanced/metastatic NSCLC in China. What's new? The global KEYNOTE‐042 clinical study helped establish single‐agent pembrolizumab, an anti‐PD‐1 monoclonal antibody, as a standard first‐line treatment option in patients with previously untreated PD‐L1‐positive locally advanced/metastatic non–small‐cell lung cancer (NSCLC) without EGFR/ALK aberrations. Because disease characteristics and responses to anticancer therapy may differ between Asian and other populations, there is a need to evaluate these treatments specifically in Asian patients. Here, the authors show that pembrolizumab also improved overall survival and was better tolerated than chemotherapy among Chinese patients with PD‐L1 TPS ≥1% in the KEYNOTE‐042 study. These data support first‐line pembrolizumab monotherapy for PD‐L1‐positive advanced/metastatic NSCLC in China. [ABSTRACT FROM AUTHOR]

Background: Post hoc analysis of the LUX-Lung 3 and 6 (LL3/6) Phase III trials showed that tolerability-guided dose-adjustments of afatinib reduced treatment-related adverse events (TRAEs) without affecting progression-free survival (PFS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). The current post hoc analysis evaluated outcomes of tolerability-guided dose adjustments of afatinib in patients enrolled in the LL3/6/7 trials in Chinese centers. Patients and Methods: Patients enrolled in LL3/6/7 had advanced EGFR mutation-positive NSCLC. LL3 and LL7 recruited patients globally (including China) and LL6 enrolled Asian patients from China, Thailand, and South Korea. In LL3 and LL6, patients were randomized to afatinib 40 mg/day or cisplatin-based chemotherapy. In the Phase IIb LL7 trial, patients were randomized to afatinib 40 mg/day or gefitinib. Tolerability-guided dose adjustments were permitted for TRAEs, and PFS was the primary endpoint. This post hoc analysis pooled data from patients enrolled in Chinese centers in LL3/6/7 and analyzed the frequency and severity of TRAEs before and after afatinib dose reductions during the first 6 months. PFS and overall survival (OS) were compared for patients who had a dose reduction in the first 6 months and those who did not. Results: Overall, 299 patients were enrolled in Chinese centers; 68 (23%) had afatinib dose reductions to < 40 mg/day in the first 6 months. Prior to dose reduction, 55/68 patients (81%) experienced grade ≥ 3 TRAE versus 13/68 (19%) after dose reduction. Grade ≥ 3 TRAEs were much more common in patients with than in those without dose reduction. Median PFS was 11.0 months in both groups, and median OS did not differ significantly: 23.1 months in patients with a dose reduction and 26.9 months in those without a dose reduction. Conclusion: Tolerability-guided afatinib dose adjustment is an effective strategy to reduce TRAEs without affecting efficacy in Chinese patients. [ABSTRACT FROM AUTHOR]

Purpose: Do-not-resuscitate (DNR) orders are an important part of end-of-life care (EOL) for patients with incurable advanced lung cancer. The aim of this study was to investigate the clinical factors related to the acceptance of DNR orders by Chinese patients.Methods: This study was a retrospective analysis involving patients with advanced-stage (IIIB or IV) lung cancer who died in hospital at our center from August 2004 through August 2014. The patients' clinical characteristics and DNR forms were reviewed.Results: Of the 348 patients enrolled, 260 (74.7 %) provided DNR orders signed only by surrogates. The signing rate of DNR orders increased annually. The median interval from signing a DNR order to death was 1 day (range, 0-72 days). Patients with poor performance status (PS) (≥2) 1 week prior to death (OR, 3.395; 95 % CI, 1.536-7.502, P = 0.003) and relatively longer overall survival (OS) (>3 months) (OR, 2.464; 95 % CI, 1.566-4.472, P < 0.001) were more likely to sign DNR orders. CPR was performed on 10.3 % (27/260) of patients with DNR orders, and was withheld in 22.7 % (20/88) of patients without DNR orders.Conclusions: The DNR order-signing rate has been increasing annually among terminal patients with lung cancer in China. DNR orders, all of which were signed by surrogates, were more likely to be accepted by patients with slowly deteriorating disease and longer OS. More effort should be taken to help patients and medical professionals establish a sensible understanding of EOL care, including DNR orders, at earlier points during the disease course. [ABSTRACT FROM AUTHOR]

Since the discovery of epidermal growth factor receptor mutations and epidermal growth factor receptor tyrosine kinase inhibitors, lung cancer treatment in China has entered the precision era. However, novel targeted agents based on novel biomarkers still need to be developed. In the current study, the authors review the biomarker features of lung cancer in the Chinese population and the novel agents that are aimed at novel targets. Furthermore, they discuss issues that require improvement for the production of novel drugs and provided future directions for development in China. Cancer 2015;121:3089-96. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Recently, non-smoking-related lung cancer was classified as an independent disease entity because it is different from tobacco-associated lung cancer. Non-smoking-related lung cancer occurs more often in women than men, and the predominant histological type is adenocarcinoma (ADC) rather than squamous cell carcinoma. Most of the driver gene alterations that have been identified in ADC in never-smokers include epidermal growth factor receptor mutations, KRAS mutations, echinoderm microtubule-associated protein like 4/anaplastic lymphoma kinase fusion, and ROS1 fusion, among others. Meanwhile, significant progress has been made in the treatment of ADC. However, in comparison with ADC, no such available molecular targets exist for smoking-associated lung cancer, for which treatment strategies are limited. Next-generation sequencing has been widely applied to the discovery of more genetic profiles of lung cancers. This review summarizes the differences between smoking-related and non-smoking-related lung cancer as follows: different somatic mutation burdens, C:G→A:T transversions, common and novel driver genes, and treatment strategies. Overall, smoking-related lung cancer is more complicated than non-smoking-related lung cancer. Furthermore, we review the prevalence of driver genes in smoking-associated and non-smoking-associated lung cancers in the Chinese population. Cancer 2015;121:3069-79. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Over the past 10 years, the Chinese Government, academic organizations, and biopharmaceutical companies have tried to transition the nation from a consumer of generic drugs into a developer of innovative therapies. Here, we present a timeline of recent innovative cancer drug development, with a particular focus on four case studies that have reshaped perceptions of what can be done in China. We present metrics comparing China with other countries alongside analysis of what national authorities are doing to close the gap in areas where China still lags behind the West. [ABSTRACT FROM AUTHOR]

Background. Substantial progress has been made in the treatment of malignancies in the People’s Republic of China in recent years.The goal of this study was to identify the extent to which national treatment guidelines are being used to customize patient care in lung cancer and to analyze the reasons for treatment disparities. Methods. Patient characteristics and treatments were investigated retrospectively for the period from October 2004 to January 2013 using the outpatient database of the Guangdong Lung Cancer Institute (GLCI) in China. Results. A total of 2,535 outpatients with lung cancer were studied in this retrospective analysis. The treatment disparity was 45.3%. Overall, 20.6% of patients with stage I non-small cell lung cancer (NSCLC) were overtreated, and 20.1% of stage II patients were undertreated. Only 19.6% of stage IIIA patients and 30.7% of stage IIIB patients underwent the recommended combination of chemotherapy and radiotherapy, respectively. For advanced NSCLC, the greatest treatment disparity appeared in the second-line setting and beyond. Patients who were positive for epidermal growth factor receptor (EGFR) and receiving EGFR tyrosine kinase inhibitors experienced significant prolongation of survival compared with patients who were EGFR negative or whose EGFR mutation status was unknown (hazard ratio: 0.79; p 5 .037). The treatment disparities were significantly larger among patients aged younger than 65 years and in patients from developing regions compared with patients aged 65 years and older and from developed regions, respectively (p , .001, p 5 .046). The difference in treatment disparity was statistically significant between GLCI and other hospitals (p , .001). Conclusion. This retrospective study of a large number of patients from an outpatient oncology database demonstrated large disparities in the treatment of lung cancer in China. It is important to develop a new guideline for recommendations that are based on resource classification. [ABSTRACT FROM AUTHOR]

Background A satisfactory biopsy determines the state-of-the-art management of lung cancer in this era of personalized medicine. This study aimed to investigate the suitability and efficacy of computed tomography ( CT)-guided core needle biopsy in clinical management. Methods A cohort of 353 patients with clinically suspected lung cancer was enrolled in the study. Patient factors and biopsy variables were recorded. Epidermal growth factor receptor ( EGFR) gene mutations and echinoderm microtubule-associated protein-like 4 ( EML4)-anaplastic lymphoma kinase ( ALK) rearrangement were detected in tumor specimens. Adequacy of biopsic obtainment for clinical trial screening and tissue bank establishment were reviewed. Results Overall diagnostic accuracy of malignancy achieved 98.5%. The median biopsy time of the cohort was 20 minutes. In patients with non-small cell lung cancer ( NSCLC), 99.3% (287/289) were diagnosed as specific histologic subtypes, and two patients (0.7%) were determined as NSCLC not otherwise specified ( NOS). EGFR mutations were analyzed in 81.7% (236/289) of patients with NSCLC, and 98.7% (233/236) showed conclusive results. EML4- ALK gene fusion was tested in 43.9% (127/289) of NSCLC patients, and 98.4% (125/127) showed conclusive results: 6.4% (8/125) of those had gene fusion. Ninety-six NSCLC patients participated in clinical trial screening and provided mandatory tumor slides for molecular profiling. Pathological evaluation was fulfilled in 90 patients (93.8%); 99.4% (320/322) of patients with malignancy provided extra tissue for the establishment of a tumor bank. Conclusions CT-guided core needle biopsy provided optimal clinical management in this era of translational medicine. The biopsic modality should be prioritized in selected lung cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: Lorlatinib, a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated robust overall and intracranial antitumor activity in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) previously treated with an ALK inhibitor in a global phase 1/2 study (NCT01970865) and a multicenter phase 2 study conducted in China (NCT03909971). We report updated 3-year follow-up data from the phase 2 study., Materials and Methods: Chinese patients with locally advanced or metastatic ALK-positive NSCLC that progressed after crizotinib as the only prior ALK inhibitor (cohort 1) or after 1 non-crizotinib ALK inhibitor (cohort 2), were enrolled in the study. All patients received lorlatinib 100 mg once daily., Results: At data cutoff, of 109 enrolled patients, the median duration of follow-up for progression-free survival (PFS) was 35.8 months in cohort 1 (n = 67) and 33.1 months in cohort 2 (n = 42). Median PFS (95% CI) per independent central review was 26.3 months (16.6-35.9) and 5.6 months (2.9-12.4), respectively. The median duration of follow-up for overall survival (OS) was 36.4 months and 37.5 months, respectively. Median OS (95% CI) was not reached (NR; NR-NR) and 21.9 months (11.9-NR), respectively. Median intracranial time to progression (95% CI) was NR (NR-NR) and NR (9.7 months-NR), respectively. No new safety signals emerged with long-term treatment., Conclusion: The long-term data confirm robust overall and intracranial clinical activity of lorlatinib, with no new safety signals emerging. These results support using lorlatinib in Chinese patients with previously treated ALK-positive NSCLC with or without brain metastases., Clinicaltrials: gov NCT03909971., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC., Methods: This two-part (phase 2a and 2b), multicentre, single-arm, open-label, phase 2 study was done in 29 centres in China. Eligible participants were adults (aged ≥18 years) with histologically or cytologically confirmed ROS1-rearranged, locally advanced or metastatic stage IIIB-IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 2 or less. Patients who had previously received no or one ROS1 inhibitor were enrolled into phase 2a, and patients who were naive to ROS1 inhibitor therapy were enrolled into phase 2b cohort 1. Participants in phase 2a received 80, 120, 160, or 210 mg foritinib succinate (foritinib) orally once daily over 21-day cycles; patients in phase 2b received the recommended phase 2 dose of 160 mg. The primary endpoint was objective response rate, assessed by the independent review committee in the full analysis set (ie, all participants who received at least one dose of study treatment). The safety analysis set included all participants who received at least one dose of study treatment and had available safety assessments. This study is ongoing and is registered with ClinicalTrials.gov, NCT04237805., Findings: Between March 26, 2020, and Dec 29, 2022, 104 patients were enrolled and treated. Six patients who had previously received more than one ROS1 inhibitor were enrolled in phase 2a before a protocol amendment stating that patients in this phase should have received no more than one ROS1 inhibitor; these patients were included in the safety analysis but excluded from the efficacy analysis of the ROS1-inhibitor-pretreated cohort. Therefore, the efficacy analysis set (n=98) included 42 patients from phase 2a (17 who were ROS1 inhibitor naive and 25 who had previously received ROS1 inhibitor) and 56 patients from phase 2b cohort 1. In phase 2a, the objective response rate was 94% (95% CI 71-100; 16 of 17 patients) in patients who were ROS1 inhibitor naive and 40% (21-61; ten of 25) in patients who had previously received ROS1 inhibitor. In phase 2b cohort 1, the objective response rate was 88% (95% CI 76-95; 49 of 56 patients). In a prespecified exploratory analysis in 41 patients with CNS metastases at baseline, the objective response rate was 100% (95% CI 48-100; five of five patients) in patients in phase 2a who were ROS1 inhibitor naive, 40% (16-68; six of 15) in patients in phase 2a who had previously received ROS1 inhibitor, and 90% (70-99; 19 of 21) in patients in phase 2b cohort 1. Grade 3-4 treatment-related adverse events occurred in 33 (32%) of 104 patients; the most common were hyperglycaemia (12 [12%] patients) and electrocardiogram prolonged QT interval (six [6%]). Serious treatment-related adverse events occurred in 11 (11%) patients, with hyperglycaemia (six [6%]) being most common. No treatment-related adverse events led to death., Interpretation: Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases., Funding: Fosun Pharma, Wanbang Biopharmaceuticals, and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer., Competing Interests: Declaration of interests Y-LW reports grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, and Roche, and personal fees from AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Hengrui, Merck Sharp & Dohme, Pfizer, Roche, and Sanofi, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Purpose: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR ) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results., Methods: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR -activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data., Results: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively., Conclusion: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Background: In the phase 3 CheckMate 078 study, nivolumab showed significant overall survival (OS) benefit and superior tolerability versus docetaxel in a predominantly Chinese patient population with non-small cell lung cancer (NSCLC). However, data on long-term outcomes with immunotherapy in Asian patients are limited. We report 2-year efficacy and safety data., Methods: Patients with advanced/metastatic NSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks; n = 338) or docetaxel (75 mg/m 2 every 3 weeks; n = 166) until progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was OS; secondary endpoints included progression-free survival, objective response rate, and safety., Results: After 25.9 months minimum follow-up, 21 patients (6 %) remained on nivolumab versus 0 on docetaxel. Median OS was 11.9 months with nivolumab versus 9.5 months with docetaxel (HR: 0.75; 95 % CI: 0.61-0.93); 2-year OS rates were 28 % versus 18 %, respectively. Survival benefits were observed across a variety of predefined subgroups. At 2 years, 39 % and 0 % of responders had ongoing responses with nivolumab and docetaxel, respectively. Grade 3-4 treatment-related adverse events occurred in 12 % of patients with nivolumab versus 47 % with docetaxel, leading to discontinuation in 4 % and 5 % of patients, respectively. No new treatment-related deaths occurred., Conclusion: At 2 years, nivolumab maintained a favorable safety profile and continued to demonstrate superior OS versus docetaxel in this predominantly Chinese patient population with previously treated NSCLC. These data are consistent with long-term outcomes from the global CheckMate 017/057 studies., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10 - 26 ). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10 -3 ). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression., Patients and Methods: ASCEND-6, a phase 1/2, single-arm study, included adult Chinese patients with stage IIIB or IV ALK+ NSCLC pretreated with crizotinib as the last therapy (irrespective of prior chemotherapies [≤2]). Primary endpoints were pharmacokinetics (PK), safety, and tolerability. Key secondary endpoint was overall response rate (ORR; investigator assessed)., Results: Of the 103 enrolled patients, all received prior crizotinib, 70 % received ≥1 prior chemotherapy regimen, and 63.1 % had brain metastases at baseline. In the phase 1 component, 20 patients completed a 5-day PK run-in period. Median T max (n = 16) was ∼6 h; geometric means of AUC 0-24 h (n = 16) and C max (n = 16) at steady state were 22,000 ng*h/mL and 1080 ng/mL, respectively. In the final analysis, median follow-up time was 34 months (range: 27.8-40.6). The ORR was 41.7 % (95 % confidence interval [CI]: 32.1-51.9), and median progression-free survival was 7.2 months (95 % CI: 4.1-7.5). Median overall survival was 17.5 months (95 % CI: 10.8-24.3). Most frequent adverse events, regardless of study drug relationship (mostly grade 1/2), were diarrhea (74.8 %), vomiting (62.1 %), alanine transaminase increased (59.2 %), aspartate transaminase increased (58.3 %), and nausea (58.3 %)., Conclusions: Ceritinib PK in Chinese patients is consistent with those observed in the global ASCEND-1 study. Ceritinib was well tolerated and showed durable responses in Chinese patients with ALK+ NSCLC who progressed after crizotinib and ≤2 prior lines of chemotherapy., (Copyright © 2020. Published by Elsevier B.V.)

Background: Tislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy., Methods: The purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1., Results: As of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2-21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types., Conclusions: Tislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors., Trial Registration Number: CTR20160872., Competing Interests: Competing interests: LS, JG, QZ, HP, YY, YB, TL, QZ, JZ, YS, XH, SW, JW, AZ, DY, TS, and Y-LW have nothing to declare. YG, SY, ZW, and JL are employees of BeiGene., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC., Materials and Methods: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients., Results: Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits., Conclusion: In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized., Methods: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted., Results: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib., Conclusions: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated factors associated with (i) the likelihood of receiving a gene aberration test and (ii) the choice of treatment between chemotherapy and targeted therapy in patients with non-small cell lung cancer (NSCLC) in China., Materials and Methods: This cross-sectional study analyzed data previously extracted from the medical charts of patients with unresectable Stage IIIB/IV nonsquamous NSCLC discharged from one of 12 tertiary hospitals in China between August 2015 and March 2016. Logistic regressions were applied to investigate factors associated with receiving a gene aberration test and the treatment decision., Results: Data from 932 patients were analyzed. Patients were less likely to have a gene aberration test if they had a histologic subtype other than adenocarcinoma or a hospital waiting time for test results of >5 days. Patients were more likely to receive tyrosine kinase inhibitor (TKI) treatment than chemotherapy if they had a positive result for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase gene aberration testing. EGFR positive patients were more likely to receive TKI treatment than chemotherapy if they did not have insurance for TKI or pemetrexed treatment, and more likely to receive chemotherapy than TKI treatment if they had a waiting time for test results of >5 days. EGFR wild-type/unknown patients receiving chemotherapy were more likely to receive pemetrexed if they attended a hospital in a developed area or had insurance for pemetrexed., Conclusion: In this real-world setting in China, the choice of first-line treatment for advanced NSCLC was appropriately guided by gene aberration testing for most patients. However, gene aberration testing and the treatment decision were influenced by practical factors such as hospital location, the waiting time for test results, and insurance coverage, which should be addressed to ensure optimal patient care., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1-defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

Background/aim: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in cancer. Buparlisib (BKM120), an oral pan-PI3K inhibitor, inhibits proliferation of human cancer in preclinical models. Studies of buparlisib in Western and Japanese adults with advanced solid tumors established a recommended dose of 100 mg/day and showed an acceptable safety profile and evidence of efficacy. This phase I dose-escalation/expansion study aimed to establish the maximum tolerated dose (MTD) of single-agent, once daily oral buparlisib in Chinese patients with advanced solid tumors., Materials and Methods: Patients (n=32; primary tumor site: lung (n=15), breast (n=10) or head and neck (n=7); ≥2 prior lines of antineoplastic therapy (n=26)) received 80 mg (n=15) or 100 mg (n=17) daily buparlisib., Results: Five patients experienced dose-limiting toxicities: grade (G)3 depression (n=1), G2 hyperglycemia (n=3) and G3 hyperglycemia (n=1). Most frequent buparlisib-related adverse events were hyperglycemia (n=18; 56%), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase (n=9; 28%), as well as anxiety (n=6; 19%); most common buparlisib-related G3/4 adverse events: hyperglycemia (n=3; 9%), ALT and AST increase (n=2; 6%), as well as gamma-glutamyltransferase increase (n=2; 6%). Best response was stable disease (SD) in 10 patients (31%)., Conclusion: The MTD of buparlisib was declared as 100 mg/day. Safety, efficacy and pharmacokinetic data from this study were similar to those previously reported in Western and Japanese populations., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: Some population-based studies involving lung cancer patients have reported that inherited susceptibility is responsible for the familial aggregation observed in non-smoking lung cancer patients; however, it has been found that the false-negative rates in clinic-ascertained probands are significantly lower than population-ascertained probands. In this clinic-based study, we sought to determine the relationship between a family history of cancer and lung cancer risk in Chinese never-smokers., Methods: In this clinic-based case-control study, all 318 probands and 509 controls were Chinese. The data on demographic characteristics, age, gender, race, lung disease history, living environment, occupational exposure, and smoking history were collected from a structured questionnaire. Multiple conditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs after adjusting for possible confounders., Results: The risk of lung cancer was increased in individuals with a family history of lung (aOR, 3.21; p<0.001) or any other cancer (aOR, 1.79; p<0.001). Analyses were carried out using stratified relative gender; first-degree female relatives tended to have a higher risk than first-degree male relatives. Similarly, the aOR for a female developing a malignant tumor was two times greater than controls., Conclusions: Our analysis provides further evidence of the importance of genetic factors underlying lung cancer in patients who are never-smokers, especially in patients with a maternal history of cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Genome-wide association studies (GWAS) have determined a new single nucleotide polymorphism (SNP) called VTI1A (rs7086803) that induces lung cancer susceptibility in nonsmoking women in Asia. This study aimed to evaluate the association between the VTI1A gene and the susceptibility of Chinese patients to lung cancer; it was also conducted to investigate the relationship between VTI1A SNP and adiponectin receptor 1 expression., Methods: A total of 887 subjects were enrolled in this study. VTI1A (rs7086803) genotypes were determined by genotyping. Overall survival (OS) was evaluated using Kaplan-Meier analysis with a log-rank test., Results: Multivariate regression analysis results indicated that the AA genotype of VTI1A (rs7086803) polymorphism was associated with an increased risk of developing non-small cell lung carcinoma (NSCLC) compared with the GG genotype (AA vs. GG: odds ratio [OR] = 2.020; 95% confidence interval [95% CI], 1.033-3.949, p = 0.037). The AA genotype of VTI1A (rs7086803) in smokers predicted significantly shorter OS (median survival time [MST]: AA 9.8 months, AG 19.3 months, GG 12.2 months, p = 0.017). Adiponectin receptor 1 expression in tumor tissues with the AA genotype was significantly lower than that for other genotypes (mean rank: AA 18.55, AG 25, GG 45.76, p = 0.001)., Conclusions: The presence of the allele A of VTI1A (rs7086803) may be the allele contributing to the risk of lung cancer susceptibility in Chinese population. Smoking lung cancer patients with the AA genotype of VTI1A gene (rs7086803) had a poor survival rate. Adiponectin receptor 1 expression may be correlated with the susceptibility of the allele A of VTI1A.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk., (Published 2014. This article is a US Government work and, as such, is in the public domain of the United States of America.)

Purpose: The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies., Patients and Methods: Patients age ≥ 18 years with locally advanced, metastatic, or recurrent advanced nonsquamous non-small-cell lung cancer (NSCLC) were randomly assigned to receive carboplatin (area under the curve, 6) intravenously and paclitaxel (175 mg/m(2)) intravenously (CP) on day 1 of each 3-week cycle, for ≤ six cycles, plus placebo (Pl+CP) or bevacizumab (B+CP) 15 mg/kg intravenously, on day 1 of each cycle, until progression, unacceptable toxicity, or death. The primary end point was progression-free survival (PFS); secondary end points were objective response rate, overall survival, exploratory biomarkers, safety., Results: A total of 276 patients were randomly assigned, 138 to each arm. PFS was prolonged with B+CP versus Pl+CP (median, 9.2 v 6.5 months, respectively; hazard ratio [HR], 0.40; 95% CI, 0.29 to 0.54; P < .001). Objective response rate was improved with B+CP compared with Pl+CP (54% v 26%, respectively). Overall survival was also prolonged with B+CP compared with Pl+CP (median, 24.3 v 17.7 months, respectively; HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP (HR, 0.27; 95% CI, 0.12 to 0.63) in EGFR mutation-positive tumors and 8.3 and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21 to 0.53), in wild-type tumors. Safety was similar to previous studies of B+CP in NSCLC; no new safety signals were observed., Conclusion: The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and resulted in a clinically meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC., (© 2015 by American Society of Clinical Oncology.)

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and Met inhibitors have enabled progress in the management of advanced non-small-cell lung cancer (NSCLC). However, the clinical benefits of these agents are not uniform across the NSCLC spectrum. Thus, we evaluated the prognostic effect of mesenchymal-epithelial transition (MET) expression in Asian NSCLC patients with or without EGFR mutation., Methods: Frozen tumor tissues were collected from 92 patients with surgical resection and 10 with lymph node biopsy. Mutations in exons 18-21 in the EGFR-tyrosine kinase domain and MET expression were analyzed by using sequencing and immunohistochemistry, respectively., Results: The MET overexpression rate was 51% in NSCLC patients. MET-positive patients had poorer overall survival than MET-negative patients (29.8 versus 69.1 months, χ = 7.420, p = 0.006) in patients with wild-type EGFR. However, no statistically significant difference was found in EGFR mutant patients (35.0 versus 35.9 months, χ = 0.114, p = 0.735). Multivariate analysis showed that stage, MET expression, and sex were independent prognostic factors in patients with wild-type EGFR (χ = 32.896, p < 0.001)., Conclusions: These results suggest that MET expression has different prognostic significance in patients with differing EGFR mutation status. Whether MET inhibitors should be given early to NSCLC patients with EGFR wild-type needs further investigation.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC., Methods: This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m(2) on day 1 and day 8 plus cisplatin 75 mg/m(2) on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393., Findings: 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7-13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1-6·7; hazard ratio 0·28, 95% CI 0·20-0·39; p<0·0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 [14·6%] of 239 patients), diarrhoea (13 [5·4%]), and stomatitis or mucositis (13 [5·4%]), compared with neutropenia (30 [26·5%] of 113 patients), vomiting (22 [19·5%]), and leucopenia (17 [15·0%]) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6·3%) patients in the afatinib group and nine (8·0%) patients in the gemcitabine and cisplatin group., Interpretation: First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population., Funding: Boehringer Ingelheim., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The efficacy of pemetrexed in the second-line treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) has been shown to be similar to that of docetaxel in a recent study; additionally, pemetrexed was associated with much better safety and toxicity profiles. Here, the survival without common toxicity criteria grade 3/4 toxicity (SWT) data from a post hoc analysis of this recent prospective NSCLC study in Chinese patients is reported. This post hoc analysis differs from the main study; it focuses on the nonsquamous population to align with the current approval for pemetrexed in China., Methods: A total of 154 patients with nonsquamous NSCLC received either pemetrexed (500 mg/m(2) intravenously (IV)) or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. SWT was analyzed using Kaplan-Meier and univariate Cox methods., Results: Patients treated with pemetrexed had a longer median SWT than patients treated with docetaxel (7.4 months versus 1.2 months; unadjusted hazard ratio = 0.59, 95% confidence interval (CI): 0.41-0.84; P = 0.003). At 12 and 18 months, the SWT event-free probability for pemetrexed patients (18 months: 24.5%, 95%CI 13.9%-36.6%, vs. 12.3%, 95% CI 4.8%-23.6%) was greater than that for docexatel patients (12 months: 37.3%, 95% CI 26.5%-48.0%, vs. 23.3%, 95% CI 14.4-33.4). The progression-free survival without common toxicity criteria grade 3/4 toxicity (PFS-WT) was also statistically significantly longer for patients treated with pemetrexed than patients treated with docetaxel (1.9 months vs. 1.1 months, P = 0.002)., Conclusions: Chinese patients with nonsquamous NSCLC disease treated with pemetrexed had improved SWT beyond 6 months than those receiving docetaxel. This analysis supports a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of Chinese nonsquamous NSCLC patients.

Introduction: Computed tomography screening can detect lung cancer that is curable. However, some studies demonstrated that the risk for false-positives was about 50%. To make screening more efficient, we sought to create a forecasting model for individuals with different risks for lung cancer., Methods: We used multiple logistic regression analysis to identify independent predictors and to develop a prediction model. The pathological diagnoses in Guangdong Lung Cancer Institute were consecutively chosen as probands. All first-degree relatives of probands and their spouses were included as subjects. We divided the probands and their spouses into three subgroups according to the odds ratios (ORs), and the accuracy of lung cancer predictions for patients within the subgroups increased synchronously., Results: There were 633 proband pedigrees and 565 spouse pedigrees. Independent predictors of lung cancer included sex (OR, 1.6; 95% confidence interval [CI], 1.1-2.3), smoking history (light smoker: OR, 1.1; 95% CI, 0.7-1.8; heavy smoker: OR, 4.7; 95% CI, 3.1-7.1), lung disease history (OR, 5.3; 95% CI, 2.8-10.0), occupational exposure (OR, 1.6; 95% CI, 1.1-2.2), and number of affected individuals among first-degree relatives (n = 1: OR, 2.1; 95% CI, 1.3-3.4; n ≥ 2: OR, 4.7; 95% CI, 0.5-41.2). The accuracy of the pretest probability increased for those with higher ORs: low-OR subgroup, 68.3%; mid-OR subgroup, 84.0%; and high-OR subgroup, 91.9%., Conclusions: Our prediction rule is recommended for estimating the pretest probability of lung cancer, thereby facilitating early screening.

Aim: In the IRESSA Pan-Asia Study (IPASS), 1217 patients in East Asia with pulmonary adenocarcinoma who were never-smokers or ex/light-smokers received first-line gefitinib (250 mg/day) or carboplatin/paclitaxel (area under the curve 5/6; 200 mg/m(2) ). Efficacy analyses were pre-planned in patients in China., Methods: In China, 372 patients (30.6% of the overall group) were randomized. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), health-related quality of life (HRQoL), symptom improvement, safety and tolerability., Results: For patients in China, PFS did not significantly differ from the overall IPASS population (interaction test P= 0.427). PFS was numerically longer (hazard ratio [HR] 0.79; 95% CI 0.62-1.01; P= 0.065; median PFS 6.8 months for both treatments) and ORR significantly higher (ORR 44.6 vs 29.8%; odds ratio 1.88; 95% CI 1.22-2.89; P= 0.004) for gefitinib than carboplatin/paclitaxel. OS (mature data) was similar for both treatments (HR 0.92; 95% CI 0.73-1.17; P= 0.511; median OS gefitinib 18.1 months vs 18.3 months carboplatin/paclitaxel). HRQoL improvement rates favored gefitinib; symptom improvement rates were similar for both treatments. Gefitinib had a more favorable tolerability profile than carboplatin/paclitaxel. Efficacy by epidermal growth factor receptor biomarker status (exploratory analyses) was difficult to interpret due to low patient numbers with known biomarker status., Conclusion: For the Chinese subgroup of IPASS, gefitinib demonstrated improved PFS and ORR, similar OS, higher HRQoL, similar symptom improvement rates and a more favorable tolerability profile than carboplatin/paclitaxel, generally consistent with the overall IPASS population., (© 2012 Wiley Publishing Asia Pty Ltd.)

Introduction: Over the past 10 years, there have been significant advances in clinical trials and translation research on lung cancer in China. These advances have changed the clinical practice of lung cancer treatment. Translation research has clarified many molecular mechanisms of lung cancer development, growth and metastasis. Based on these results, a few cancer-driving molecular targets were identified. Many new compounds that directly or indirectly target these driver genes have been developed and tested., Areas Covered: Studies from the literature and ongoing work from the author's group were reviewed. This was with the aim of outlining the current state of a clinical trial cooperative group for lung cancer and highlighting some important clinical trials and biomarker research that have changed lung cancer clinical practice in China., Expert Opinion: For biomarker-driven clinical research, it is important to identify subgroups of patients who are most likely to benefit from given targeted therapies. In this setting, the rapid identification and translation of validated biomarkers will be integral to the treatment of lung cancer. It is also important to utilize results from high-quality clinical research groups to enrich patients lives and to perform these challenging clinical trials.

Introduction: First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL., Methods: Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival., Results: The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months., Conclusions: The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Real-time reverse transcription polymerase chain reaction and immunohistochemistry were used to evaluate the messenger RNA (mRNA) and protein expression levels of total cyclin D1 and its splice variants (cyclin D1a and cyclin D1b) in 102 paired malignant and nonmalignant tissues from patients with non-small cell lung cancer, respectively. The expression levels of total cyclin D1 and its splice variants were significantly up-regulated in malignant tissues than in nonmalignant tissues at both mRNA and protein levels. Although the expression levels of cyclin D1a were higher than those of cyclin D1b, the relative expression ratios of cyclin D1b mRNA between malignant and nonmalignant lung tissues were obviously higher than those of cyclin D1a mRNA. Analysis of variance showed that cyclin D1b mRNA expression was significantly associated with the histologic grade, lymph node metastasis, distant metastasis, and tumor stage of patients, whereas cyclin D1a mRNA expression was not related to clinicopathologic characteristics except sex. Patients with cyclin D1b mRNA expression above the median value had shorter survival than those below the median value (P = .033). Similarly, cyclin D1b immunopositivity was also associated with histologic grade, and patients with immunostaining positivity for cyclin D1b showed poor survival (P = .005). Multivariate analysis demonstrated that cyclin D1b immunopositivity was an independent risk factor in survival of patients with non-small cell lung cancer (P = .018). Our data show that cyclin D1b, rather than canonical cyclin D1a, might contribute to the development of non-small cell lung cancer. Cyclin D1b would be a better prognostic indicator for non-small cell lung cancer as compared to total cyclin D1 or cyclin D1a.