ALK-Fusion Small Cell Lung Cancer Responding to ALK-Targeted Therapy

What happened, in summary

A 41-year-old woman who had never smoked was diagnosed in January 2022 with extensive-stage small cell lung cancer. She first received 6 cycles of etoposide and cisplatin, with thoracic radiation during treatment. The cancer partially shrank, but about 7 months after completing chemoradiation it returned in the left hilar area.

She received another 5 cycles of the original chemotherapy and initially had stable disease, but the cancer progressed again. Two cycles of nab-paclitaxel did not control it. Blood-based molecular testing then identified an EML4-ALK fusion, an unusual finding in small cell lung cancer. She next received irinotecan with the immunotherapy tislelizumab and the anti-angiogenic drug anlotinib. This combination produced another partial response, but progression returned by December 2023.

In early 2024 she entered a clinical trial and received a bispecific immunotherapy targeting PD-1 and CTLA-4. The cancer progressed again, and brain metastases appeared. Because of the ALK fusion, she then started the ALK inhibitor iruplinalkib. Imaging showed a partial response, including control of the advanced disease. At the latest follow-up, she was still taking iruplinalkib and had remained without progression on this treatment for more than 8 months. The case suggests that rare ALK rearrangements can sometimes provide a treatment option even in small cell lung cancer.