A new era of treating advanced lung cancer is upon us.

Transl Lung Cancer Res 2018;7(Suppl 3):S202-S205 tlcr.amegroups. com From the adaption of chemotherapy in the 1990’s after the landmark meta-analysis (1) to the pivotal randomized trial pointing to “dealer’s choice” for platinum-doublet regimens (2), followed by treatment refinement using molecular profiling and targeted therapy for defined sub-populations (3,4), we now have the emergence of a new era to treat advanced non-small cell lung cancer (NSCLC). Checkpoint inhibitor therapy has moved from 2nd line and beyond salvage therapy, to first-line therapy in advanced NSCLC with the results of the KEYNOTE-189 trial (5) on the heels of KEYNOTE-024 (6). Coupled with the recent presentations o f KEYNOTE-042 (7 ) and KEYNOTE-407 (8 ) and other published front-line checkpoint inhibitor studies including CheckMate-026 (9), CheckMate-227 (10), and IMpower150 (11), I will put into context the results of KEYNOTE-189 in the present state of clinical practice. The KEYNOTE-189 study randomized metastatic non-squamous NSCLC patients without sensitizing EGFR or ALK aberrations who had not received prior treatment for metastatic disease in a double-blind fashion 2:1 to either platinum-pemetrexed with 200 mg pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for a total of 35 cycles with pemetrexed (5). Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance score of 0–1 and the absence of symptomatic central nervous system metastases, history of noninfectious pneumonitis that required the use of glucocorticoids, active autoimmune disease, or active use of systemic immunosuppressive treatment. Patients were also excluded if they had received more than 30 Gy of radiotherapy to the lung in the previous 6 months prior to enrollment. Programmed death-ligand 1 (PDL1) immunohistochemical expression [tumor proportion score (TPS), ≥1% vs. <1%], choice of platinum-based drug (cisplatin vs. carboplatin), and smoking history (never vs. former or current) were patient randomization stratification factors. Investigators could choose between cisplatin 75 mg/m or carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute), while pemetrexed was dosed at 500 mg/m. Radiographic response was assessed by RECIST 1.1 criteria (12). The two primary end points were overall survival (OS) (any cause of death from the time of randomization) and progression-free survival (PFS) (as assessed by earliest event, either by independent central radiologic review or any cause of death, from the time from randomization). The study allowed crossover for patients in the placebo-combination group who had verified disease progression. Overall, 965 patients were screened for enrollment. The main reasons for exclusion prior to randomization included: presence of an activating epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) aberration, ECOG performance status score ≥2, lack of written, informed consent, and active central nervous system metastasis and/or carcinomatous meningitis. Enrollment of 616 patients occurred between February 26, 2016 and March 6, 2017 at 118 sites, mostly from Europe and North America. A TPS score ≥1% was present in 63% of these Editorial