Case 2: Assessing HER2 IHC Expression and Comorbidity Risks in Treatment Sequencing

In this portion of the program, Dr. Jacob Sands introduces a second case that illustrates the complexities of treating metastatic non-small cell lung cancer in a patient with significant comorbidities and HER2 expression without mutation. The patient is a 70-year-old woman with a 25–pack-year smoking history, ECOG 2 status, mild COPD, hypertension, and a prior immune-related pneumonitis episode following checkpoint inhibitor therapy. After first-line carboplatin, paclitaxel, and atezolizumab resulted in stable disease for 7 months, she received second-line docetaxel and ramucirumab with 4 months of control. Broad NGS testing did not identify HER2 mutation, but immunohistochemistry demonstrated HER2 IHC 3+ expression in at least half of tumor cells. With systemic progression and her underlying pulmonary vulnerabilities, Dr. Sands underscores the importance of carefully balancing HER2-directed therapeutic options with the elevated risk of TKI-associated lung toxicity, setting the stage for a nuanced discussion of next-line treatment strategies.