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Background: The IPASS study reported that gefitinib provided superior progression-free survival (PFS) compared with carboplatin and paclitaxel in a clinically selected lung cancer patient population; the benefit was restricted to patients with epidermal growth factor receptor gene (EGFR)-mutant tumours because patients with wild-type (WT) tumours had inferior outcomes. The current study compared PFS for pemetrexed plus cisplatin induction therapy followed by gefitinib as maintenance therapy versus gefitinib monotherapy as first-line treatments in patients with non-squamous non-small cell lung cancer. Methods: Patients (n=236) with unknown EGFR mutation status were randomised 1:1 to pemetrexed plus cisplatin for six cycles or gefitinib. Patients without progressive disease after six cycles received gefitinib maintenance therapy. Primary endpoint analysis (Wilcoxon test after 169 PFS events) provided 80% power if the true hazard ratio (HR) was 0.65. Tissue samples were analysed for EGFR mutation status. Findings: Baseline characteristics were balanced across treatment arms. 50 (68%) of 74 samples had mutations. Primary PFS analysis showed no significant difference between treatment arms (Wilcoxon p= 0.217). Unadjusted HR was 0.85 (95% confidence interval [CI] 0.63-1.13). During most of the study, the Kaplain Meier curve for pemetrexed plus cisplatin remained above the curve for gefitinib. In a prespecified subgroup analysis, EGFR-by-treatment interaction as statistically significant (p=0.008), showing treatment effect significantly differed by EGFR status. The PFS HR favoured pemetrexed plus cisplatin in EGFR-mutated and EGFR-WT patients, but the magnitude of benefit was greater in EGFR-WT patients (EGFR-mutated: HR 0.83 [95% CI 0.42-1.62], p=0.585; EGFR-WT: HR 0.18 [95% CI 0.06-0.51], p=0.001). HRs for intention to treat (ITT) and EGFR-mutated patients were not constant and should be interpreted with caution. Interpretation: In the ITT population, the PFS difference was not statistically significant. In the biomarker assessable population, EGFR-WT patients did not benefit from front-line EGFR tyrosine kinase inhibitor treatment. Identification of EGFR mutational status is key for management of advanced non-squamous non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background There is an expanding list of therapeutically relevant biomarkers for NSCLC and effective molecular profiling is paramount. We sought to comprehensively and prospectively evaluate the molecular epidemiology of NSCLC in Asia and ascertain the extent of access to relevant therapies. The study is being conducted by the Asian Thoracic Oncology Research Group (ATORG) – an academic co-operative lung cancer trials group in Asia. Methods ATORG-001 is a prospective, multi-centre study of NSCLC patients (pts) throughout Asia. Eligible pts must have good performance status (ECOG ≤2), adequate organ function and ≤3 prior lines of cytotoxic chemotherapy. Archival tissue specimens are sent to a central laboratory in Singapore (Singapore General Hospital) for profiling, consisting of NGS with the Oncomine Focus Assay (52 gene panel including fusions) and PD-L1 immunohistochemistry. Results are returned to investigators in a clinically relevant timeframe. Baseline demographics, pre-existing molecular profile and prior treatment details are collected. Treatment and pt outcomes are followed for 2 years. Recruitment commenced in Jan 2019 in 3 sites (National Cancer Centre Singapore, Chinese University of Hong Kong, University Malaya Medical Centre). We report an interim analysis for the first 27 of a planned 500 pts. Results As of 01 Jul 2019, 27 pts have enrolled with median age 67 yrs (range 46-79), 59% male, 81% adenocarcinoma, 52% stage IV, 37% non-smokers, median lines of prior therapy 1 (range 0-6) and 85% with no known oncogenic driver. Pre-existing mutation status was known in 89% for EGFR and 63% for ALK. Median turnaround time from tissue acquisition to profiling results was 22 days (range 15-74). New alterations were most common in KRAS (19%), MYC (15%), CDK4 (7%) and ERBB2 (7%). Potentially actionable new alterations were found in 7 (26%) pts, including KRAS G12C mutation (7%), BRAF G469A mutation (4%), ERBB2 exon 20 insertion (4%), ERBB2 amplification (4%), FGFR2 amplification (4%) and MET exon 14 skipping mutation (4%). Conclusions Enrolment is ongoing with additional sites and countries planned to comprehensively evaluate the molecular epidemiology of NSCLC in Asia. Legal entity responsible for the study Asian Thoracic Oncology Research Group. Funding Asian Thoracic Oncology Research Group, Novartis. Disclosure A.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Introduction: Most published guidelines for genomic biomarker testing in NSCLC reflect the disease epidemiology and treatments readily available in Europe and North America. Nevertheless, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the EGFR occur at a higher prevalence in Asia than in other world regions. Although medical associations such as the International Association for the Study of Lung Cancer, European Society for Medical Oncology, and American Society of Clinical Oncology have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia., Methods: This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts for clinicians working in Asia to improve patient care. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1, and others are discussed., Results: These recommendations are divided into nonmetastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma. Owing to the higher prevalence of EGFR mutations in Asia, the experts emphasized the need for EGFR testing to include not just common mutations (exon 19 deletions and L858R substitutions) but also other uncommon EGFR mutations. In addition to the assessment of biomarkers in the tumor tissue, the role of assessing tumor biomarkers by liquid biopsy is discussed., Conclusion: This consensus provides practical recommendations for biomarker testing in nonmetastatic and metastatic Asian NSCLC patients., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)