Case Presentation: Sandra, a 54-Year-Old Never-Smoker with HER2-Mutant NSCLC and Brain Metastases

Dr. Deborah Doroshow presents Sandra, a 54-year-old never-smoker diagnosed 14 months ago with stage IVA non-small cell lung cancer (NSCLC), adenocarcinoma subtype. Currently on medical leave from her medical receptionist position, Sandra has anxiety managed with sertraline, gastroesophageal reflux disease treated with famotidine, normal hepatic function, and Eastern Cooperative Oncology Group performance status of 1. She has high-deductible Affordable Care Act insurance with a $6,000 annual deductible and is concerned about medication costs.At diagnosis, her community oncologist ordered limited biomarker testing (EGFR, ALK, ROS1, KRAS, PD-L1) due to insurance coverage concerns for comprehensive next-generation sequencing. Results showed KRAS wild-type and PD-L1 tumor proportion score of 10%; notably, HER2 testing was not performed. She received first-line carboplatin, pemetrexed, and pembrolizumab for 4 cycles, followed by pemetrexed maintenance, achieving partial response with 12 months of progression-free survival.Sandra now presents with disease progression: enlarging lung mass, new contralateral pulmonary nodules, morning headaches, and word-finding difficulty. Magnetic resonance imaging brain reveals two enhancing lesions consistent with brain metastases (12-mm left frontal, 8-mm right parietal) without significant edema or midline shift. Comprehensive next-generation sequencing at progression identified HER2 Y772_A775dup mutation with no other actionable alterations. She has undergone stereotactic radiosurgery to both brain lesions with headache improvement and been connected with oncology social work for patient assistance programs. Her priorities include maximizing response, minimizing interstitial lung disease risk, and preferring oral therapy.

In the next episode, "Incomplete Upfront Biomarker Testing in Community Practice: Consequences and Barriers," Dr. Doroshow discusses how Sandra's delayed HER2 mutation identification represents a broader pattern in community oncology.