Real-World Clinical Impact of Immune Checkpoint Inhibitors in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer After Platinum Chemotherapy

Lung cancer is the first most common malignancy in the wild word, and the leading cause of cancer-related mortality. Approximately 85% of lung cancers are non-small-cell lung cancer (NSCLC). More than half of all lung cancers in the United States are diagnosed at advanced or metastatic stage, which has a 5-year survival of 4.8%. The recommendations for systemic treatment of metastatic NSCLC (stage IV) are guided by patient performance status (PS), tumor histology, and status of tumor biomarkers. Firstline (1L) treatment with platinum-based chemotherapy has long been the standard of care. In the second-line (2L) setting after 1L chemotherapy, the efficacy and safety of antiePD-L1 therapies have been shown in several phase III clinical trials. Nivolumab was granted approval by the US Food and Drug Administration (FDA) for treatment of metastatic squamous NSCLC. In October 2015, a second PD-1 inhibitor, pembrolizumab, was granted accelerated FDA approval for treatment of PD-L1epositive NSCLC after previous platinum-based therapy. In October 2016, the FDA approved the PD-L1 inhibitor atezolizumab for treatment of metastatic NSCLC after progression with previous platinum-based therapy, largely on the basis of improved outcomes in patients who received atezolizumab in the phase III OAK trial compared with those who received docetaxel.

  Based on none have compared the overall survival (OS) before and after the availability of antiePD-L1 therapies for NSCLC in US clinical practice. The author aimed to compare the time periods before and after the FDA approval of PD-L1 inhibitors by assessing real-world treatment patterns and clinical outcomes of US patients with advanced/metastatic NSCLC who received 2L treatment after platinum-based therapy. The author collected the patients with advanced/metastatic NSCLC (stage IIIB/IV), or with early-stage NSCLC and subsequent progression to advanced/metastatic disease, between January 1, 2011 and November 30, 2017.  In total, 6306 patients in the historical cohort and 7438 patients in the current cohort diagnosed with advanced NSCLC who had received 1L platinum-based therapy with at least 6 months of follow-up were identified in the Flatiron Health database. Of these, 2357 patients (37.4%) in the historical cohort received 2L treatment, and 1123 patients (17.8%) received thirdline (3L) treatment (Figure 1). In the current cohort, 4240 patients (57.0%) received 2L treatment, and 1875 patients (25.2%) received 3L treatment.

To our knowledge, this is the first large real-world data analysis of the effect of 2L antiePD-L1 agents on patients with advanced/metastatic NSCLC after receiving platinum doublet in the 1L. The author observed that the median OS increased by 2 months (approximately 20%) since FDA approval of nivolumab, pembrolizumab, and atezolizumab. The patients who received 2L antiePD-L1 therapies were more likely to have a higher ECOG PS, which is associated with poor prognosis. AntiePD-L1 therapies have been shown to have fewer toxicity issues and more durable responses than historically available chemotherapy options. which might improve physician perception of the risk-benefit profile enough to initiate 2L therapy in patients who were previously considered too infirm for 2L chemotherapy. The separation of OS curves and improvement in median OS provides a real-world confirmation of antiePD-L1 benefits reported in clinical trials. Further follow-up of this cohort would indicate whether usage of PD-L1 therapy in 2L/3L leads to an improvement in long-term survival in the real-world setting similar to that seen in clinical trials of patients with advanced/metastatic NSCLC. 

In a word, this research revealed that survival of patients receiving 2L therapy for NSCLC in routine US clinical practice has significantly improved since the introduction of antiePD-L1 therapies. Which suggest that antiePD-L1 therapy has enabled access to treatment for patients who would previously have been considered too infirm to receive 2L therapy.