HER2-mutated lung cancer: restarting targeted therapy after lung inflammation

What happened, in summary

A 78-year-old Japanese woman had Stage IV lung adenocarcinoma with multiple brain metastases. Testing showed a HER2 exon 20 insertion, while PD-L1 was negative. She initially received carboplatin-based chemotherapy and had a partial response, then continued chemotherapy. When the brain metastases progressed, they were treated with focused Gamma Knife radiation.

A second chemotherapy later stopped controlling the lung tumor. She then began the HER2-directed treatment trastuzumab deruxtecan. Within the first treatment cycle, scans showed new inflammation in both lungs. She did not have breathing symptoms, and the findings were treated as drug-related lung inflammation. Trastuzumab deruxtecan was paused and steroids were started.

After the lung inflammation improved, the cancer began worsening again. She and her family chose to restart trastuzumab deruxtecan with steroid coverage. The lung tumor and lymphatic spread improved, and the lung inflammation did not recur.

She received 9 cycles in total after the treatment course was resumed. Trastuzumab deruxtecan was eventually stopped because the cancer progressed, but the rechallenge allowed her to continue the HER2-directed therapy for additional time.