The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy - characterized by some benefit but only rare durable responses - was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field.

Keywords: Cancer immunotherapy; Consensus statement; Guideline; Lung cancer; Non-small cell lung cancer.

Fig. 1

Advanced/metastatic NSCLC treatment algorithm. All treatment options shown may be appropriate and final selection of therapy should be individualized based on patient eligibility, prior treatment, and treatment availability at the treating physician’s discretion. These algorithms represent consensus sequencing suggestions by the panel. (1) All patients should be evaluated by a multidisciplinary team to determine histological subtype, identify targetable driver mutations, and perform PD-L1 testing. The Task Force unanimously agreed that all newly diagnosed patients should receive testing for PD-L1. (2) For patients with squamous NSCLC with TPS ≥ 50%, the Task Force supports pembrolizumab monotherapy first-line. When FDA approval is granted, the Task Force also supports pembrolizumab in combination with carboplatin & (nab-) paclitaxel in specific cases. (3) When approved by the FDA, the Task Force recommends combination pembrolizumab + pemetrexed & (nab-) paclitaxel first-line in patients with squamous histology and PD-L1 TPS < 50%. (4) In patients with non-squamous cell NSCLC tumors positive for EGFR, ALK, or ROS1 aberrations, appropriate targeted therapy should be administered. (5) Patients with squamous or non-squamous cell NSCLC who have progressed on platinum-containing chemotherapy and who have not previously received a checkpoint inhibitor should be considered for atezolizumab, nivolumab, or pembrolizumab. (6) The Task Force unanimously agreed that patients with non-squamous cell NSCLC without EGFR, ALK, or ROS1 aberrations and TPS < 50% should receive combination pembrolizumab + pemetrexed & carboplatin. (7) In patients with non-squamous cell NSCLC without EGFR, ALK, or ROS1 aberrations and TPS ≥ 50%, the Task Force recommends pembrolizumab monotherapy, but recognizes that combination pembrolizumab + pemetrexed & carboplatin can be appropriate in specific cases