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In this phase II, single arm trial (ACTRN12617000720314), we investigate if alternating osimertinib and gefitinib would delay the development of resistance to osimertinib in advanced, non-small cell lung cancer (NSCLC) with the epidermal growth factor receptor (EGFR) T790M mutation (n = 47) by modulating selective pressure on resistant clones. The primary endpoint is progression free-survival (PFS) rate at 12 months, and secondary endpoints include: feasibility of alternating therapy, overall response rate (ORR), overall survival (OS), and safety. The 12-month PFS rate is 38% (95% CI 27.5–55), not meeting the pre-specified primary endpoint. Serial circulating tumor DNA (ctDNA) analysis reveals decrease and clearance of the original activating EGFR and EGFR-T790M mutations which are prognostic of clinical outcomes. In 73% of participants, loss of T790M ctDNA is observed at progression and no participants have evidence of the EGFR C797S resistance mutation following the alternating regimen. These findings highlight the challenges of treatment strategies designed to modulate clonal evolution and the clinical importance of resistance mechanisms beyond suppression of selected genetic mutations in driving therapeutic escape to highly potent targeted therapies.

INTRODUCTION: Evidence regarding the role of exercise in pancreatic cancer (PanCa) is limited and is derived exclusively under tightly controlled research conditions. This study aimed to quantify adherence, adverse events, and changes in physical and psychological outcomes in any patients with PanCa referred to undertake exercise during nonsurgical treatment. METHODS: The study involved 22 patients with localized or metastatic PanCa undertaking a clinic-based exercise program during chemotherapy or chemoradiotherapy. The program included supervised aerobic and resistance exercise undertaken twice weekly for 12 wk and a 12-wk follow-up with supervised exercise optional dependent on patient preference and condition. Patients were monitored for adherence and adverse events. Objective and patient-reported outcomes were assessed at baseline, 12 wk, and 24 wk. RESULTS: A total of 251 sessions were attended by 19 patients over the first 12 wk (attendance rate, 55%). Complete case analyses indicated significant ( P < 0.05) improvements in functional ability (5.2%-17.2%), muscle strength (16.9%-25.1%), and static balance (6.8%). There were no significant changes in body composition or patient-reported outcomes except for sleep quality, which deteriorated; however, at an individual level, several patients had clinically relevant improvements in cancer-related fatigue and quality of life. Patients who continued with supervised exercise to week 24 largely preserved improvements in functional ability, muscle strength, and static balance. No serious adverse events resulted from the exercise program. CONCLUSIONS: Individualized, supervised aerobic and resistance exercise in a clinic-based setting appears to be safe and may improve or maintain physical and psychological health in patients with PanCa undergoing nonsurgical treatment.

Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence-based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways.Copyright © 2019 John Wiley & Sons Australia, Ltd

Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence-based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways.Copyright © 2019 John Wiley & Sons Australia, Ltd

Stage III non-small cell lung cancer (NSCLC) makes up a third of all NSCLC cases and is potentially curable. Despite this 5-year survival rates remain between 15% and 20% with chemoradiation treatment alone given with curative intent. With the recent exciting breakthroughs in immunotherapy use (durvalumab) for stage III NSCLC, further improvements in patient survival can be expected. Most patients with stage III NSCLC present initially to their general practitioner (GP). The recommended time from GP referral to first specialist appointment is less than 14 days with treatment initiated within 42 days. Our review found that there is a shortfall in meeting these recommendations, however a number of initiatives have been established in Australia to improve timely and accurate diagnosis and treatment patterns. The lung cancer multidisciplinary team (MDT) is critical to consistency of evidence-based diagnosis and treatment and can improve patient survival. We aimed to review current patterns of care and clinical practice recommendations for stage III NSCLC across Australia and identify opportunities to improve practice in referral, diagnosis and treatment pathways.