Effectiveness of a self-determination theory-based smoking cessation intervention plus instant messaging via mobile application for smokers with cancer: Protocol for a pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This protocol is for a study to test the effectiveness of a self-determination theory-based intervention (quit immediately or progressively) plus instant messaging (WhatsApp or WeChat) to help smokers with cancer to quit smoking. DESIGN: This will be a multi-centre, two-arm (1:1), single-blind, pragmatic, individually randomized controlled trial. SETTING: Taking part will be specialist outpatient clinics in five major hospitals in different location-based clusters in Hong Kong. PARTICIPANTS: The sample will include 1448 Chinese smokers living with cancer attending medical follow-ups at outpatient clinics. INTERVENTIONS: The intervention group will receive brief advice (approximately 5-8 minutes) from research nurses in the outpatient clinics and then be invited to choose their own quit schedules (immediate or progressive). During the first 6-month follow-up period they will receive instant messaging with smoking cessation advice once per week for the first 3 months, and thereafter approximately once per month. They will also receive four videos, and those opting to quit progressively will receive a smoking reduction leaflet. The control group will also receive brief advice but be advised to quit immediately, and instant messaging with general health advice during the first 6-month follow-up period using the same schedule as the intervention group. Participants in both groups will receive smoking cessation leaflets. MEASUREMENTS: The primary outcome is biochemically validated smoking abstinence at 6 months, as confirmed by saliva cotinine level and carbon monoxide level in expired air. Secondary outcomes include biochemically validated smoking abstinence at 12 months, self-reported 7-day point prevalence of smoking abstinence at 6 and 12 months, self-reported ≥ 50% reduction of cigarette consumption at 6 and 12 months and quality of life at 6 and 12 months. All time-points for outcomes measures are set after randomization. COMMENTS: The results could inform research, policymaking and health-care professionals regarding smoking cessation for patients living with cancer, and therefore have important implications for clinical practice and health enhancement.

Inhalable paclitaxel nanoagglomerate dry powders for lung cancer chemotherapy: Design of experiments-guided development, characterization and in vitro evaluation.

Conventional intravenous chemotherapy for lung cancer frequently results in inefficient drug penetration into primary lung tumors and severe systemic toxicities. This study reports the development of inhalable paclitaxel (PTX) nanoagglomerate dry powders (PTX-NADP) for enhanced pulmonary delivery of PTX chemotherapy to lung tumors using full factorial Design of Experiments. PTX nanoparticles were fabricated by flash nanoprecipitation with the aid of N-polyvinylpyrrolidone (PVP) and curcumin (CUR) as stabilizer and co-stabilizer respectively, and subsequently agglomerated into inhalable dry powders via co-spray drying with methylcellulose. The optimized PTX-NADP formulation exhibited acceptable aqueous redispersibility (redispersibility index = 1.17 ± 0.02) into âˆ¼ 150 nm nanoparticles and superb in vitro aerosol performance [mass median aerodynamic diameter (MMAD) = 1.69 ± 0.05 µm and fine particle fraction (FPF) of 70.89 ± 1.72 %] when dispersed from a Breezhaler® at 90 L/min. Notably, adequate aerosolization (MMAD < 3.5 µm and FPF > 40 %) of the optimized formulation was maintained when dispersed at reduced inspiratory flow rates of 30 - 60 L/min. Redispersed PTX nanoparticles from PTX-NADP demonstrated enhanced in vitro antitumor efficacy and cellular uptake in A549 lung adenocarcinoma cells without compromising tolerability of BEAS-2B normal lung epithelial cells towards PTX chemotherapy. These findings highlight the potential of inhaled PTX-NADP therapy to improve therapeutic outcomes for lung cancer patients with varying levels of pulmonary function impairment.

Prevalence, incidence, and survival analysis of interstitial lung diseases in Hong Kong: a 16-year population-based cohort study.

Background: Published data on the epidemiology of interstitial lung disease (ILD) in Asia is scarce. Understanding the epidemiology is important for authorities in the health management planning. This study aimed to estimate the prevalence, incidence, and survival of ILD in Hong Kong from 2005 to 2020 and evaluate the change of trend over time. Methods: In this retrospective cohort study, we identified ILD patients between 2005 and 2020 using a territory-wide electronic health record database. Prevalence, incidence rates, and age- and sex-standardised incidence rates with United Nations population in 2020 as a reference were estimated. Trends in prevalence and incidence were analysed using joinpoint regression and the average annual percent change (AAPC) was estimated. Median survival, and risk factors of mortality were evaluated using Cox proportional hazard regression. Findings: We identified 5924 patients and included 5884 of them for analysis. The prevalence of ILD increased from 24.7 to 33.6 per 100,000 population from 2005 to 2020 with an AAPC of 1.94 (95% confidence interval, CI: 1.69-2.34). The standardized incidence rate decreased from 5.36 to 2.57 per 100,000 person from 2005 to 2020 (AAPC -3.56, 95% CI, -4.95 to -1.78). The median survival of ILD was 2.50 (95% CI, 2.32-2.69) years. Male, older age, higher Charlson comorbidity index, and IIP subtype were associated with increased mortality with statistical significance. Interpretation: This study provided the first epidemiological evaluation of ILD in Hong Kong. Further studies on ILD in multiple Asian cities and countries are warranted. Funding: None.

Increased exacerbations of bronchiectasis following recovery from mild COVID-19 in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Respiratory viral infection is a common trigger of bronchiectasis exacerbation. Knowledge of the intermediate to long-term effect of COVID-19 on bronchiectasis is poor. METHODS: A retrospective cohort study of patient records was conducted to assess the frequency of bronchiectasis exacerbation following recovery from mild-to-moderate COVID-19. The exacerbation frequency at baseline, using 2019 and 2019-2021 data, was compared with that during the 1 year following recovery. RESULTS: A total of 234 adult patient records who had a confirmed diagnosis of bronchiectasis were identified, of whom 52 (22.2%) were classified as the COVID-19 group. Patients with COVID-19 had significantly more frequent annual exacerbations of bronchiectasis (total exacerbations and hospitalizations). Compared with 2019-2021 data, the total exacerbation frequency decreased by 0.1 ± 0.51 per year among non-COVID-19 patients but increased by 0.68 ± 1.09 per year among the COVID-19 group (p < 0.001). Compared with 2019 only data, exacerbation frequency decreased by 0.14 ± 0.79 per year among non-COVID-19 patients but increased by 0.76 ± 1.17 per year in the COVID-19 group, p < 0.001. The annual frequency of hospitalization for bronchiectasis increased by 0.01 ± 0.32 per year among non-COVID-19 patients and increased by 0.39 ± 1.06 per year in the COVID-19 group (p < 0.001) compared with 2019 to 2021 data. When compared with only 2019 data, it remained unchanged at 0 ± 0.43 per year among non-COVID-19 patients but increased to 0.38 ± 1.12 per year among COVID-19 patients (p < 0.001). CONCLUSION: Mild-to-moderate COVID-19 was associated with an increase in frequency of bronchiectasis exacerbation and frequency of hospitalizations following recovery.

Real-World Effectiveness Study of Nirmatrelvir-Ritonavir or Molnupiravir in Hospitalized Unvaccinated Patients with Chronic Respiratory Diseases and Moderate COVID-19 at Presentation.

Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases. Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023. Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups. Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.

Integrated continuous manufacturing of inhalable remdesivir nanoagglomerate dry powders: Design, optimization and therapeutic potential for respiratory viral infections.

While inhalable nanoparticle-based dry powders have demonstrated promising potential as next-generation respiratory medicines, erratic particle redispersibility and poor manufacturing reproducibility remain major hurdles hindering their translation from bench to bedside. We developed a one-step continuous process for fabricating inhalable remdesivir (RDV) nanoagglomerate dry powder formulations by integrating flash nanoprecipitation and spray drying. The nanosuspension formulation was optimized using a three-factor Box-Behnken design with a z-average particle size of 233.3 ± 2.3 nm and < 20% size change within six hours. The optimized inhalable nanoagglomerate dry powder formulation produced by spray drying showed adequate aqueous redispersibility (Sf/Si = 1.20 ± 0.01) and in vitro aerosol performance (mass median aerodynamic diameter of 3.80 ± 0.58 µm and fine particle fraction of 39.85 ± 10.16%). In A549 cells, RDV nanoparticles redispersed from the inhalable nanoagglomerate powders displayed enhanced and accelerated RDV cell uptake and negligible cytotoxicity at therapeutic RDV concentrations. No statistically significant differences were observed in the critical quality attributes of the inhalable nanoagglomerate powders produced from the continuous manufacturing and standalone batch modes. This work demonstrates the feasibility of large-scale continuous manufacturing of inhalable nanoagglomerate dry powder formulations, which pave the way for their clinical translation.

Lung Cancer Screening in Asia: An Expert Consensus Report.

INTRODUCTION: The incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. METHOD: A group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. RESULTS: Significant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. CONCLUSIONS: Asian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.

Breaking the Invisible Barriers: Unleashing the Full Potential of Immune Checkpoint Inhibitors in Oncogene-Driven Lung Adenocarcinoma.

The rapid development of targeted therapy paved the way toward personalized medicine for advanced non-small cell lung cancer (NSCLC). Lung adenocarcinoma (ADC) harboring actionable genetic alternations including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma virus (ALK) and c-ros oncogene 1 (ROS1) treated with tyrosine kinase inhibitors (TKIs) incurred lesser treatment toxicity but better therapeutic responses compared with systemic chemotherapy. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) have also shown an increase in overall survival (OS) for NSCLC patients. However, acquired resistance to these targeted therapies remains a major obstacle to long-term maintenance treatment for lung ADC patients. The emergence of immune checkpoint inhibitors (ICIs) against programmed cell death protein 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) has changed the treatment paradigm for NSCLC tumors without actionable genetic alternations. Clinical studies have suggested, however, that there are no survival benefits with the combination of targeted therapy and ICIs. In this review, we will summarize and discuss the current knowledge on the tumor immune microenvironment and the dynamics of immune phenotypes, which could be crucial in extending the applicability of ICIs for this subpopulation of lung ADC patients.

Blood eosinophil percentage as a predictor of response to inhaled corticosteroid in bronchiectasis.

INTRODUCTION: The role of inhaled corticosteroid (ICS) among patients with bronchiectasis remains controversial. There is limited evidence of using baseline eosinophil count (absolute and percentage) as a marker to predict the role of ICS among patients with bronchiectasis. METHODS: A retrospective case-control study was conducted in a major regional hospital and tertiary respiratory referral centre in Hong Kong, including 140 Chinese patients with noncystic fibrosis (CF) bronchiectasis, to investigate the exacerbation risks of bronchiectasis among ICS users and nonusers with different baseline eosinophil counts. RESULTS: ICS user had significantly lower risk to develop bronchiectasis exacerbation with adjusted odds ratio (OR) of 0.461 (95% confidence interval [CI] 0.225-0.945, p-value 0.035). Univariate logistic regression was performed for different cut-offs of blood eosinophil count (by percentage) from 2% to 4% (with a 0.5% grid each time). Baseline eosinophil 3.5% was found to be the best cut-off among all with adjusted OR of 0.138 (95% CI = 0.023-0.822, p-value = 0.030). CONCLUSION: Baseline eosinophil count of 3.5% might serve as a marker to predict the benefits of ICS on exacerbation risk among patients with non-CF bronchiectasis.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

Hospital Burden of Chronic Obstructive Pulmonary Disease in Hong Kong - The Trend from 2006 to 2014.

Background: Chronic obstructive pulmonary disease (COPD) is a common cause for hospital admission. This study aims to review the hospital burden of COPD in Hong Kong (HK) and the trend from year 2006 to 2014. Methods: A multi-center, retrospective study of the characteristics of COPD patients discharged from the public hospitals of HK from year 2006 to 2014. Anonymized data retrieval and analysis were performed. The demographic data of the subjects, use of health-care resources, ventilatory support, medications used and mortality of the subjects were analyzed. Results: Total patient headcount (HC) and admission number reduced from 10,425 and 23,362 in year 2006 to 9613 and 19,771, respectively, in 2014. There was a progressive reduction of female COPD HC from 2193 (21%) in year 2006 to 1517 (16%) in 2014. The utilization of non-invasive ventilation (NIV) increased rapidly and peaked in 2010 (29%) and decreased thereafter. There was a rapid increase in the prescription of long-acting bronchodilators (from 15% to 64%). COPD and pneumonia were the top causes of death, but death due to pneumonia was rapidly increasing while death due to COPD was progressively decreasing over the period. Conclusion: COPD HC and admission number (particularly in female patients) decreased progressively from year 2006 to 2014. There was also a decreasing trend of severity of disease as reflected by lower NIV use (after year 2010) and lower mortality rate due to COPD. Reduced smoking prevalence and tuberculosis (TB) notification rate in the community in the past might have reduced the incidence and severity of COPD and the hospital burden of disease. We observed an increasing trend of mortality due to pneumonia in COPD patients. Appropriate and timely vaccination programs are recommended for COPD patients as in the general elderly population.

Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting.

While molnupiravir (MOV) and nirmatrelvir-ritonavir (NMV-r) were developed for treatment of mild to moderate COVID-19 infection, there has been a lack of data on the efficacy among unvaccinated adult patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. A territory-wide retrospective cohort study was conducted in Hong Kong to investigate the efficacy of MOV and NMV-r against severe outcomes of COVID-19 in unvaccinated adult patients with chronic respiratory diseases. A total of 3267 patients were included. NMV-r was effective in preventing respiratory failure (66.6%; 95% CI, 25.6-85.0%, p = 0.007), severe respiratory failure (77.0%; 95% CI, 6.9-94.3%, p = 0.039) with statistical significance, and COVID-19 related hospitalization (43.9%; 95% CI, -1.7-69.0%, p = 0.057) and in-hospital mortality (62.7%; 95% CI, -0.6-86.2, p = 0.051) with borderline statistical significance. MOV was effective in preventing COVID-19 related severe respiratory failure (48.2%; 95% CI 0.5-73.0, p = 0.048) and in-hospital mortality (58.3%; 95% CI 22.9-77.4, p = 0.005) but not hospitalization (p = 0.16) and respiratory failure (p = 0.10). In summary, both NMV-r and MOV are effective for reducing severe outcomes in unvaccinated COVID-19 patients with chronic respiratory diseases.

Changes in Etiology and Clinical Outcomes of Pleural empyema during the COVID-19 Pandemic.

Healthcare-seeking behavior changed during the COVID-19 pandemic and might alter the epidemiology of pleural empyema. In this study, the incidence, etiology and outcomes of patients admitted for pleural empyema in Hong Kong in the pre-COVID-19 (January 2015-December 2019) and post-COVID-19 (January 2020-June 2022) periods were compared. Overall, Streptococcus pneumoniae was the predominant organism in <18-year-old patients, while Streptococcus anginosus, anaerobes and polymicrobial infections were more frequent in adults. In the post-COVID-19 period, a marked decline in the incidence of pleural empyema in children was observed (pre-COVID-19, 18.4 ± 4.8 vs. post-COVID-19, 2.0 ± 2.9 cases per year, p = 0.036), while the incidence in adults remained similar (pre-COVID-19, 189.0 ± 17.2 vs. post-COVID-19, 198.4 ± 5.0 cases per year; p = 0.23). In the post-COVID-19 period, polymicrobial etiology increased (OR 11.37, p < 0.0001), while S. pneumoniae etiology decreased (OR 0.073, p < 0.001). In multivariate analysis, clinical outcomes (length of stay, ICU admission, use of intrapleural fibrinolytic therapy, surgical intervention, death) were not significantly different in pre- and post-COVID-19 periods. In conclusion, an increase in polymicrobial pleural empyema was observed during the pandemic. We postulate that this is related to the delayed presentation of pneumonia to hospitals.

Worsening of asthma control after recovery from mild to moderate COVID-19 in patients from Hong Kong.

BACKGROUND: While there are postulations that asthma is potentially associated with severe coronavirus disease 2019 (COVID-19), there has been conflicting results from studies on the impact mild-to-moderate COVID-19 on asthma control after recovery. METHODS: A case control study on the association between mild-to-moderate COVID-19 and asthma control post infection was conducted. The primary outcome was a reduction in Asthma Control Test (ACT) score by ≥ 3 points post-COVID infection. The secondary outcomes included the change in ACT score, the proportion of patient with ACT score who dropped to ≤ 15 on enrolment visit and the need for escalation of asthma maintenance therapy. RESULTS: Out of the total of 221 adult patients with asthma recruited, 111 had mild-to-moderate COVID-19 within 30 to 270 days prior to study enrolment. The adjusted odds ratio (aOR) for a reduction in ACT score by ≥ 3 points after COVID-19 was 3.105 (95% CI = 1.385-6.959, p = 0.006). The odds of escalation of asthma maintenance therapy by at least 1 Global Initiative for Asthma (GINA) step was 4.733 (95% CI = 1.151-19.467, p = 0.031) and asthma patient are more likely to become uncontrolled after COVID-19 [aOR = 5.509 (95% CI = 1.061-28.600, p = 0.042)]. CONCLUSION: Mild-to-moderate COVID-19 among asthma patients, upon recovery, was associated with worsening of asthma symptom, lower ACT score, a higher need for escalation of asthma maintenance therapy and more uncontrolled asthma.

Efficacy of mRNA and Inactivated Whole Virus Vaccines Against COVID-19 in Patients with Chronic Respiratory Diseases.

Background: While different COVID-19 vaccines have been developed, there has been lack of data on the efficacy comparison between mRNA and inactivated whole virus vaccine among patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. Methods: This was a retrospective case control study on the efficacy of BNT162b2 (mRNA vaccine) and CoronaVac (inactivated whole virus vaccine) against COVID-19 in patients with chronic respiratory diseases. A total of 327 patients were included, with 109 patients infected with COVID-19 matched with 218 patients without COVID-19. The co-primary outcomes were vaccine effectiveness against symptomatic COVID-19, COVID-19-related hospitalization and COVID-19-related respiratory failure. Vaccine effectiveness was calculated using the formula (1-adjusted odds ratio) x 100. Results: Patients who received at least 2 doses of CoronaVac had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination, with adjusted odds ratio (OR) of 0.189 (95% CI = 0.050-0.714, p = 0.014) and 0.128 (95% CI = 0.026-0.638, p = 0.012) respectively. Patients who received at least 2 doses of BNT162b2 had lower risk of being hospitalized for COVID-19 and developing respiratory failure than those who did not have vaccination with adjusted OR of 0.207 (95% CI = 0.043-0.962, p = 0.050) and 0.093 (95% CI = 0.011-0.827, p = 0.033) respectively. There was no statistically significant difference in the risks of being hospitalized for COVID-19 and developing respiratory failure between patients who received at least 2 doses of CoronaVac or BNT162b2. Conclusion: BNT162b2 and CoronaVac vaccines are effective in preventing hospitalization for COVID-19 and respiratory failure complicating COVID-19 among patients with chronic respiratory diseases. Patients with chronic respiratory diseases should be encouraged to have COVID-19 vaccination.

Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non-small cell carcinoma.

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced nonsquamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Bevacizumab and pembrolizumab can be added to chemotherapy for patients with nonsquamous NSCLC with benefits but there has not been any dedicated head-to-head comparison between pembrolizumab-pemetrexed-platinum (PAC) and bevacizumab-pemetrexed-platinum (BAC) on their efficacy and safety. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 451 patients with advanced stage nonsquamous NSCLC that received first-line pemetrexed and platinum with or without bevacizumab or pembrolizumab. Patients who received pemetrexed-platinum (AC) were compared with those who received PAC and BAC. The primary endpoint was the progression-free survival (PFS). RESULTS: The median PFS for patients that received PAC was significantly longer than those who received BAC and AC (9 months vs. 6.8 months vs. 4.8 months, p < 0.05 among all three groups), with OR of 0.578 (95% CI, 0.343-0.976; p = 0.040) and 0.430 (95% CI, 0.273-0.675; p < 0.001) when compared to BAC and AC, respectively. Patients who received PAC also had a higher disease control rate and higher likelihood to receive continuation maintenance therapy than those on AC. There is no statistically significant difference in the grade 3 to 4 toxicity among the three treatment groups. CONCLUSIONS: Although both regimens are superior to pemetrexed-platinum alone, data from this retrospective single center study suggested a better PFS in  advanced stage nonsquamous NSCLC patient treated with first-line pembrolizumab-pemetrexed-platinum than bevacizumab-pemetrexed-platinum without an obvious increase in significant toxicity.