Immune Checkpoint Inhibitors Improve Survival in Non−Small Cell Lung Cancer

EVE M. SEGAL, PHARMD, BCOP, shared her expertise on the management of metastatic non−small cell lung cancer (NSCLC) and how pharmacists can maximize therapeutic outcomes in a live 2020 Directions in Oncology Pharmacy^® conference session titled Advances in Managing Metastatic Non−Small Cell Lung Cancer in the Era of Immune Checkpoint Inhibitors. Lung cancer remains the leading cause of cancer-related deaths in the United States with a 5-year relative survival of just 20.5%. In the past 5 years, numerous immune checkpoint inhibitor (ICI) regimens have been approved by the FDA for first- and second-line treatment of advanced lung cancer. In contrast with standard chemotherapy, long-term follow-up with ICI therapies showed a long-lasting effect on overall survival.

Dr Segal began the session by interpreting data on biomarker testing in NSCLC, specifically with programmed death-ligand 1 (PD-L1) expression, noting testing for PD-L1 is not required for first-line treatment. PD-1 positivity predicted a better response to ICI therapy in fewer than 30% of studies. She also noted tumor proportion score may change during treatment course or throughout disease progression.

Treatment regimens were also reviewed, including data showing the positive impact of ICIs on patient overall survival, both as monotherapy and in combination with platinum-based chemotherapy compared with traditional treatment with platinum-based doublet regimens in metastatic NSCLC. Specifically, pembrolizumab combined with pemetrexed and cisplatin or carboplatin is a preferred National Comprehensive Cancer Network category 1 recommendation for metastatic NSCLC with nonsquamous disease, a good performance status, and without contraindications to ICI treatment. Other ICIs approved by the FDA in the first-line setting include atezolizumab and nivolumab plus ipilimumab, all in combination with chemotherapy. Doublet therapy with a platinum and pemetrexed remains standard of care for patients with an Eastern Cooperative Oncology Group performance status of 2 or greater.

Dr Segal touched on phase 2 and 3 trial data that evaluated immunotherapies in the second-line treatment of metastatic NSCLC. These studies showed a significant advantage over the prior standard of care, docetaxel, and showed long-term disease control.

Dr Segal wrapped up with a discussion on the role of pharmacists in the management of the adverse effects associated with ICI. Grade 3 or higher immune-related adverse events (irAEs) occur in 20% of patients receiving anti-CTLA-4 therapy and approximately 10% to 13% of patients receiving anti-PD-1/PD-L1 therapy. Dr Segal illustrated key principles in management of irAEs including:

• Early recognition
• Determine severity of irAE using Common Terminology Criteria for Adverse Events
• Consultation of specialists for complex management
• Use of available guideline recommendations for management
• Clinical pearls for pharmacists in managing patients developing irAEs

She related that while irAEs may affect any organ system, pneumonitis and thyroiditis are more common with anti-PD-1/PD-L1 therapy and colitis is more common with anti-CTLA-4 therapy. Corticoste- roids are the backbone of management of irAEs with aggressive supportive care.