METHODS: This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients' demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis.
RESULTS: Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group performance status of 2-4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85-16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82-37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49-22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790 M mutation detected in 42.0% of them.
CONCLUSIONS: Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure.
MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.
RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.
CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.
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.
PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned.
RESULTS: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04-0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy.
CONCLUSIONS: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
METHODS: This retrospective study of patients with NSCLC from 18 major hospitals (public, private or university teaching hospitals) enrolled in Malaysia's National Cardiovascular and Thoracic Surgical Database (NCTSD) assessed the efficacy of lower doses of afatinib on treatment outcomes in a real-world clinical practice. Data on clinical characteristics, afatinib dosing, and treatment outcomes for patients included in NCTSD from 1st January 2015 to 31st December 2020 were analyzed.
RESULTS: Of the 133 patients studied, 94.7% had adenocarcinoma. Majority of the patients (60.9%) had EGFR exon 19 deletion and 23.3% had EGFR exon 21 L858R point mutation. The mean age of patients was 64.1 years and majority (83.5%) had Eastern Cooperative Oncology Group performance status of 2-4 at diagnosis. The most common afatinib starting doses were 40 mg (37.6%), 30 mg (29.3%), and 20 mg (26.3%) once daily (OD), respectively. A quarter of patients had dose reduction (23.3%) due to side effects or cost constraints. Majority of the patients had partial response to afatinib (63.2%) whilst 2.3% had complete response. Interestingly, the objective response rate was significantly higher (72.3%) with afatinib OD doses of less than 40 mg compared to 40 mg (54.0%) (P=0.032). Patients on lower doses of afatinib were two times more likely to achieve an objective response [odds ratio =2.64; 95% confidence interval (CI): 1.20-5.83; P=0.016]. These patients had a numerically but not statistically longer median time to treatment failure (TTF). Median TTF (95% CI) for the overall cohort was 12.4 (10.02-14.78) months. Median overall survival (95% CI) was 21.30 (15.86-26.75) months.
CONCLUSIONS: Lower afatinib doses (<40 mg OD) could be equally effective as standard dose in patients with EGFR-mutant advanced NSCLC and may be more suited to Asian patients, minimizing side effects that may occur at higher dosages of afatinib leading to dose interruptions and affecting treatment outcomes.
MATERIALS AND METHODS: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction.
RESULTS: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002).
CONCLUSIONS: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.
METHODS: An online/face-to-face, questionnaire-based survey of respiratory specialists and primary care physicians from eight Asian countries/region was carried out. The survey explored asthma control, inhaler selection, technique and use; physician-patient communications and asthma education. Inclusion criteria were >50% of practice time spent on direct patient care; and treated >30 patients with asthma per month, of which >60% were aged >12 years.
RESULTS: REALISE Asia (Phase 2) involved 375 physicians with average 15.9(±6.8) years of clinical experience. 89.1% of physicians reporting use of guidelines estimated that 53.2% of their patients have well-controlled (GINA-defined) asthma. Top consideration for inhaler choice was asthma severity (82.4%) and lowest, socio-economic status (32.5%). Then 54.7% of physicians checked their patients' inhaler techniques during consultations but 28.2(±19.1)% of patients were using their inhalers incorrectly; 21.1-57.9% of physicians could spot improper inhaler techniques in video demonstrations. And 79.6% of physicians believed combination inhalers could increase adherence because of convenience (53.7%), efficacy (52.7%) and usability (18.9%). Initial and follow-up consultations took 16.8(±8.4) and 9.2(±5.3) minutes, respectively. Most (85.1%) physicians used verbal conversations and least (24.5%), video demonstrations of inhaler use; 56.8% agreed that patient attitudes influenced their treatment approach.
CONCLUSION: Physicians and patients have different views of 'well-controlled' asthma. Although physicians informed patients about asthma and inhaler usage, they overestimated actual usage and patients' knowledge was sub-optimal. Physician-patient interactions can be augmented with understanding of patient attitudes, visual aids and ancillary support to perform physical demonstrations to improve treatment outcomes.
PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.
RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.
CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).
METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).
RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p
MATERIALS AND METHODS: Contrast enhanced computed tomography (CT) images of 194 multi-racial NSCLC patients (79 EGFR mutants and 115 wildtypes) were collected from three different countries using 5 manufacturers' scanners with a variety of scanning parameters. Ninety-nine cases obtained from the University of Malaya Medical Centre (UMMC) in Malaysia were used for training and validation procedures. Forty-one cases collected from the Kyushu University Hospital (KUH) in Japan and fifty-four cases obtained from The Cancer Imaging Archive (TCIA) in America were used for a test procedure. Radiomic features were obtained from BN maps, which represent topologically invariant heterogeneous characteristics of lung cancer on CT images, by applying histogram- and texture-based feature computations. A BN-based signature was determined using support vector machine (SVM) models with the best combination of features that maximized a robustness index (RI) which defined a higher total area under receiver operating characteristics curves (AUCs) and lower difference of AUCs between the training and the validation. The SVM model was built using the signature and optimized in a five-fold cross validation. The BN-based model was compared to conventional original image (OI)- and wavelet-decomposition (WD)-based models with respect to the RI between the validation and the test.
RESULTS: The BN-based model showed a higher RI of 1.51 compared with the models based on the OI (RI: 1.33) and the WD (RI: 1.29).
CONCLUSION: The proposed model showed higher robustness than the conventional models in the identification of EGFR mutations among NSCLC patients. The results suggested the robustness of the BN-based approach against variations in image scanner/scanning parameters.
METHODS: In total, 154 patients (wild-type EGFR, 72 patients; Del19 mutation, 45 patients; and L858R mutation, 37 patients) were retrospectively enrolled and randomly divided into 92 training and 62 test cases. Two support vector machine (SVM) models to distinguish between wild-type and mutant EGFR (mutation [M] classification) as well as between the Del19 and L858R subtypes (subtype [S] classification) were trained using 3DBN features. These features were computed from 3DBN maps by using histogram and texture analyses. The 3DBN maps were generated using computed tomography (CT) images based on the Čech complex constructed on sets of points in the images. These points were defined by coordinates of voxels with CT values higher than several threshold values. The M classification model was built using image features and demographic parameters of sex and smoking status. The SVM models were evaluated by determining their classification accuracies. The feasibility of the 3DBN model was compared with those of conventional radiomic models based on pseudo-3D BN (p3DBN), two-dimensional BN (2DBN), and CT and wavelet-decomposition (WD) images. The validation of the model was repeated with 100 times random sampling.
RESULTS: The mean test accuracies for M classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.810, 0.733, 0.838, 0.782, and 0.799, respectively. The mean test accuracies for S classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.773, 0.694, 0.657, 0.581, and 0.696, respectively.
CONCLUSION: 3DBN features, which showed a radiogenomic association with the characteristics of the EGFR Del19/L858R mutation subtypes, yielded higher accuracy for subtype classifications in comparison with conventional features.
METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked
PATIENTS AND METHODS: A retrospective cohort study was conducted at a tertiary care hospital in Malaysia from 1st January to 21st May 2019. Seventy admissions for COPD exacerbation involving 58 patients were analyzed.
RESULTS: The majority of the patients were male (89.8%), had a mean age of 71.95 ± 7.24 years and a median smoking history of 40 (IQR = 25) pack-years, 84.5% were in GOLD group D and 91.4% had a mMRC grading of 2 or greater. Approximately 60.3% had upper or lower respiratory tract infection as the cause of exacerbation; one in five patients had uncompensated hypercapnic respiratory failure at presentation, and 27.6% needed mechanical ventilatory support. Approximately 43.1% of patients had a history of exacerbation that required hospitalisation in the past year. The mean blood eosinophil concentration was 0.38 ± 0.46 x109 cells/L. The 30-day readmission rate was 20.3%, revisit rate to the emergency room within 30 days after discharge was 3.4%, and in-hospital mortality rate was 1.7%. Among all characteristics, a higher baseline mMRC grade (p = 0.038) and history of exacerbation in the past 1 year (p < 0.001) were statistically associated with 30-day readmission.
CONCLUSION: The 30-day readmission rate for COPD exacerbation in a Malaysian tertiary hospital is similar to the rates in high-income countries. Exacerbation in the previous year and a higher baseline mMRC grading were significant risk factors for 30-day readmission in patients with COPD. Strategies of COPD management should concentrate on improvement of symptoms control by optimisation of pharmacotherapy, and early initiation of pulmonary rehabilitation, and structured integrated care programs to reduce readmission rates.
OBJECTIVES: This study aims to examine the effect of 20-minute mindful breathing on the rapid reduction of dyspnea at rest in patients with lung cancer, chronic obstructive pulmonary disease, and asthma.
METHODS: We conducted a parallel-group, nonblinded, randomized controlled trial of standard care plus 20-minute mindful breathing vs. standard care alone for patients with moderate to severe dyspnea due to lung disease, named previously, at the respiratory unit of University Malaya Medical Centre in Malaysia, from August 1, 2017, to March 31, 2018.
RESULTS: Sixty-three participants were randomly assigned to standard care plus a 20-minute mindful breathing session (n = 32) or standard care alone (n = 31), with no difference in their demographic and clinical characteristics. There was statistically significant reduction in dyspnea in the mindful breathing group compared with the control group at minute 5 (U = 233.5, n1 = 32, n2 = 31, mean rank1 = 23.28, mean rank2 = 37.72, z = -3.574, P