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 or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer
BACKGROUND Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR‐TKI ) that is selective for both EGFR‐TKI sensitizing and T790 M resistance mutations in patients with non – small‐cell lung cancer . The efficacy of osimertinib as compared with platinum‐based therapy plus pemetrexed in such patients is unknown . METHODS In this r and omized , international , open‐label , phase 3 trial , we assigned 419 patients with T790M‐positive advanced non – small‐cell lung cancer , who had disease progression after first‐line EGFR‐TKI therapy , in a 2:1 ratio to receive either oral osimertinib ( at a dose of 80 mg once daily ) or intravenous pemetrexed ( 500 mg per square meter of body‐surface area ) plus either carboplatin ( target area under the curve , 5 [ AUC5 ] ) or cisplatin ( 75 mg per square meter ) every 3 weeks for up to six cycles ; maintenance pemetrexed was allowed . In all the patients , disease had progressed during receipt of first‐line EGFR‐TKI therapy . The primary end point was investigator‐assessed progression‐free survival . RESULTS The median duration of progression‐free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed ( 10.1 months vs. 4.4 months ; hazard ratio ; 0.30 ; 95 % confidence interval [ CI ] , 0.23 to 0.41 ; P<0.001 ) . The objective response rate was significantly better with osimertinib ( 71 % ; 95 % CI , 65 to 76 ) than with platinum therapy plus pemetrexed ( 31 % ; 95 % CI , 24 to 40 ) ( odds ratio for objective response , 5.39 ; 95 % CI , 3.47 to 8.48 ; P<0.001 ) . Among 144 patients with metastases to the central nervous system ( CNS )  , the median duration of progression‐free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed ( 8.5 months vs. 4.2 months ; hazard ratio , 0.32 ; 95 % CI , 0.21 to 0.49 ) . The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib ( 23 % ) than with platinum therapy plus pemetrexed ( 47 % ) . CONCLUSIONS Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M‐positive advanced non – small‐cell lung cancer ( including those with CNS metastases ) in whom disease had progressed during first‐line EGFR‐TKI therapy . ( Funded by AstraZeneca ; AURA3 Clinical Trials.gov number , NCT02151981 .
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 .