LAUSR

Transl Lung Cancer Res 2020 | http://dx.doi.org/10.21037/tlcr-20-874 Lung adenocarcinoma accounts for approximately 60% of all cases of non-small cell lung cancer (NSCLC). With the progression of genomic medicine, precision oncology has contributed to improve survival outcomes and quality of life in NSCLC patients. Besides molecular targeted therapy, immunotherapies are also becoming potential treatment options for advanced NSCLC patients. Pembrolizumab (brand name Keytruda) is a humanized antibody which has been approved in many advanced cancers as a potent immunotherapy. It binds to the programmed cell death protein 1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2, which helps restore the immune response. In particular, the lung cancer research in the KEYNOTE-189 trial has achieved excellent results. The KEYNOTE-189 study (1) is a randomized doubleblind phase 3 trial with epidermal growth factor receptor (EGFR)or anaplastic lymphoma kinase (ALK)-negative metastatic NSCLC patients who received no previous treatment. Patients were randomly assigned in a 2:1 ratio to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles. Subsequent maintenance therapy with either pembrolizumab or placebo combined with pemetrexed was performed until the end of 35 cycles. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival (OS) and progression-free survival (PFS). According to the latest data released at the 2020 American Society of Clinical Oncology Annual Meeting (2), as of May 20, 2019, the median followup was 18.8 (range, 0.2–38.8) months. Addition of pembrolizumab to pemetrexed-platinum reduced the risk of disease progression by 51% versus standard of care chemotherapy (9.0 vs. 4.9 months). Pembrolizumab plus pemetrexed-platinum resulted in a significant OS benefit over the placebo plus pemetrexed-platinum (22.0 vs. 10.6 months, HR =0.56; 95% CI, 0.46–0.69), despite 40.8% patients in the placebo group being cross-treated with pembrolizumab. In particular, the improvement of survival benefit of pembrolizumab combined with chemotherapy occurred independently of PD-L1 expression and a PDL1 negative population. The results of the safety analysis showed a similar incidence of grade 3–5 adverse events (AEs) in the pembrolizumab and placebo groups, at 72.1% and 66.8%, respectively. The incidence rates of grade 3–5 immune-mediated AEs and infusion-related reactions were a bit higher for the pembrolizumab group compared to the placebo group (12.1% vs. 4.5%). The most common immune-mediated AEs in the pembrolizumab group were hypothyroidism, followed by pneumonia and hyperthyroidism. At the American Association for Cancer Research (AACR) 2019 Annual Meeting, it was reported that combined immunochemotherapy with pembrolizumab led to an OS and PFS benefit in patients with liver or brain Editorial Commentary