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Malaysia is a Southeast Asian country occupying parts of the Malay Peninsula and the island of Borneo. The population of Malaysia (just over 30 million) is multi-ethnic; approximately half the population is ethnically Malay, with large minorities of Chinese, Indians, and indigenous peoples. Approximately 70% of the population is urban (Fig. 1).1 Life expectancy of Malaysians at birth is 74.9 years.2 Health care services in Malaysia are dichotomous between systems of public and private health care. Most patients (w65%) in Malaysia seek health care services in public facilities.3 However, the main drawback of public health care is a shortage of doctors and specialists in public hospitals.3 Public health care in Malaysia is heavily subsidized and offers services at a fraction of the cost of treatment in the private sector. Patients receiving treatment in private facilities, on the other hand, are usually covered by private health care insurance or make out-of-pocket payments.3 There is currently no universal-access national health care scheme in Malaysia.3 The total expenditure on health was 4.24% of the gross domestic product in 2017.4

Background : Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the firstgeneration EGFR-TKI in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Method : This is a multicentre observational study of Malaysian patients with EGFR-mutant advanced NSCLC started on first-line afatinib from 1st October 2014 to 30th April 2018. Results : The demographic and clinical characteristics of 85 patients who met the study criteria are shown in Table 1. EGFR mutations harboured by the tumours 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 the patients. 18.8% of the patients had an ECOG performance status of 2-4, 29.4% had baseline symptomatic brain metastases and 17.6% had abnormal organ function. Table 2 shows the starting dose, dose adjustment and optimal dose of afatinib. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Treatment outcome (Tables 3, 4 and 5; Figures 1 and 2) Response to afatinib The objective response rate (ORR) was 76.5% while the disease control rate (DCR) was 95.3% on first-line afatinib (Table 3). Two (2.4%) patients had complete response. Patients without baseline brain metastases had a significantly higher ORR than those with baseline brain metastases (Table 4). There was a trend for patients in whom the dose of afatinib was reduced to experience higher ORR than those without dose adjustment. On multivariate subgroup analyses involving covariates shown in Table 4, patients without symptomatic brain metastases had significantly higher ORR than that of those with symptomatic brain metastases (81.7% versus 56.0%; OR, 4.51; 95% CI, 1.45–14.00; p = 0.009); while patients with afatinib dose reduction had significantly higher ORR than that of those without dose adjustment (88.5% versus 65.3%; OR, 5.53; 95% CI, 1.32–23.24; p = 0.019). Progression-free survival 56 (65.9%) patients had PD at the time of analysis with a mPFS of 14.2 (95% CI, 11.85 – 16.55) months (Figure 1) Conclusion : Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with good response and disease control rates as well as long PFS even in patients with unfavourable clinical characteristics. The side-effects of afatinib were manageable and acquired T790M mutation was the acquired resistance mechanism in 42% of patients with PD who underwent rebiopsy