BACKGROUNDAlectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. METHODSIn a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigatorassessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. RESULTSDuring a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P = 0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). CONCLUSIONSAs compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840.

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Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively ( p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.This article has supplementary material available from