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 .
Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.
PURPOSE Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) , but progression invariably occurs . We investigated the efficacy and safety of alectinib , a potent and selective ALK inhibitor with excellent CNS penetration , in patients with crizotinib-refractory ALK-positive NSCLC . PATIENTS AND METHODS Alectinib 600 mg was administered orally twice daily . The primary end point was objective response rate ( ORR ) by central independent review committee ( IRC ) . RESULTS Of the 138 patients treated , 84 patients ( 61 % ) had CNS metastases at baseline , and 122 were response evaluable ( RE ) by IRC .  ORR by IRC was 50 % ( 95 % CI , 41 % to 59 % ) , and the median duration of response ( DOR ) was 11.2 months ( 95 % CI , 9.6 months to not reached ) . In 96 patients ( 79 % ) previously treated with chemotherapy , the ORR was 45 % ( 95 % CI , 35 % to 55 % ) . Median IRC-assessed progression-free survival for all 138 patients was 8.9 months ( 95 % CI , 5.6 to 11.3 months ) . CNS disease control rate was 83 % ( 95 % CI , 74 % to 91 % ) , and the median CNS DOR was 10.3 months ( 95 % CI , 7.6 to 11.2 months ) . CNS ORR in 35 patients with baseline measurable CNS lesions was 57 % ( 95 % CI , 39 % to 74 % ) . Of the 23 patients with baseline CNS metastases ( measurable or nonmeasurable ) and no prior radiation , 10 ( 43 % ) had a complete CNS response . At 12 months , the cumulative CNS progression rate ( 24.8 % ) was lower than the cumulative non-CNS progression rate ( 33.2 % ) for all patients . Common adverse events were constipation ( 33 % ) , fatigue ( 26 % ) , and peripheral edema ( 25 % ) ; most were grade 1 to 2 . CONCLUSION Alectinib is highly active and well tolerated in patients with advanced , crizotinib-refractory ALK-positive NSCLC , including those with CNS metastases
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 .