In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended .
There are insufficient data to recommend routine third-line cytotoxic therapy .
Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) .
Results This guideline up date reflects changes in evidence since the previous guideline .
Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study.
BACKGROUND Osimertinib ( AZD9291 ) is an oral , potent , irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations , and the EGFR Thr790Met resistance mutation . We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer ( NSCLC ) , who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor . METHODS In this phase 2 , open-label , single-arm study ( AURA2 ) , patients aged at least 18 years with central ly confirmed EGFR Thr790Met-positive mutations , locally advanced or metastatic ( stage IIIB/IV ) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy  received osimertinib 80 mg orally once daily ; treatment could continue beyond progression if the investigator observed a clinical benefit . Patients with asymptomatic , stable CNS metastases not requiring steroids were allowed to enrol . The primary endpoint was the proportion of patients achieving an objective response by blinded independent central review using Response Evaluation Criteria in Solid Tumors , version 1.1 . Response endpoints were assessed in the evaluable for response analysis set ( ie , all patients who received at least one dose of osimertinib and had measurable disease at baseline according to blinded independent central review ) . Other endpoints and safety were assessed in all patients receiving at least one osimertinib dose ( full analysis set ) . The study is ongoing and patients are still receiving treatment . This study is registered with Clinical Trials.gov , number NCT02094261 . FINDINGS Between May 20 , 2014 , and Sept 12 , 2014 , 472 patients were screened , of whom 210 started osimertinib treatment between June 13 , 2014 , and Oct 27 , 2014 ; 11 patients were excluded from the evaluable for response analysis set ( n=199 ) due to absence of measurable disease at baseline by blinded independent central review . At data cutoff ( Nov 1 , 2015 ) , 122 ( 58 % ) patients remained on treatment . The median duration of follow-up was 13·0 months ( IQR 7·6 - 14·2 ) . 140 ( 70 % ; 95 % CI 64 - 77 ) of 199 patients achieved an objective response by blinded independent central review : confirmed complete responses were achieved in six ( 3 % ) patients and partial responses were achieved in 134 ( 67 % ) patients . The most common all-causality grade 3 and 4 adverse events were pulmonary embolism ( seven [ 3 % ] ) , prolonged electrocardiogram QT ( five [ 2 % ] ) , decreased neutrophil count ( four [ 2 % ] ) , anaemia , dyspnoea , hyponatraemia , increased alanine aminotransferase , and thrombocytopenia ( three [ 1 % ] each ) . Serious adverse events were reported in 52 ( 25 % ) patients , of which 11 ( 5 % ) were investigator assessed as possibly treatment-related to osimertinib . Seven deaths were due to adverse events ; these were pneumonia ( n=2 ) , pneumonia aspiration ( n=1 ) , rectal haemorrhage ( n=1 ) , dyspnoea ( n=1 ) , failure to thrive ( n=1 ) , and interstitial lung disease ( n=1 ) . The only fatal event assessed as possibly treatment-related by the investigator was due to interstitial lung disease . INTERPRETATION Osimertinib showed clinical activity with manageable side-effects in patients with EGFR Thr790Met-positive NSCLC . Therefore , osimertinib could be a suitable treatment for patients with EGFR Thr790Met-positive disease who have progressed on an EGFR tyrosine-kinase inhibitor . FUNDING AstraZeneca
In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended .
There are insufficient data to recommend routine third-line cytotoxic therapy .
Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) .
Results This guideline up date reflects changes in evidence since the previous guideline .