Dr. Pennell on the Risks Associated With Sequential Therapy With Immunotherapy/TKIs in Lung Cancer

Nathan A. Pennell, MD, PhD, director, Lung Cancer Medical Oncology Program, Taussig Cancer Institute, Cleveland Clinic, discusses the risks that are associated with sequential therapy with immunotherapy and TKIs in lung cancer.

Patients with advanced disease who require immediate treatment but have not undergone molecular testing should not be considered for single-agent immunotherapy, says Pennell. Moreover, findings from a phase 2 trial showed that patients with EGFR-mutant lung cancer are unlikely to respond to EGFR TKIs after having received immunotherapy. 

Alternatively, some patients diagnosed with stage III disease who have not undergone molecular testingwill receive chemoradiation, followed by up to 1 year of consolidation durvalumab (Imfinzi), Pennell explains. Molecular testing is not common in the stage III setting. However, for patients who progress and are found to have a targetable alteration, there is a significant risk of putting them on a TKI. As such, if an actionable mutation is identified, during treatment with durvalumab, it’s recommended to start these patients should be started on chemotherapy alone for 3 months before being given a TKI, says Pennell. 

There are no prospective trials evaluating this specific scenario; however, these patients could develop serious complications if the TKI is started too soon following immunotherapy, Pennell concludes.