How Dynamic Therapies and Targeted Approaches Enabled Ongoing Disease Control

A 50-year-old female presented in September 2016 with post-exercise dyspnea and lower extremity paresthesia. She had no history of smoking or relevant family cancer history, but was allergic to sulfa drugs. An enhanced chest CT scan revealed a central lung mass in the right hilum region, alongside pulmonary atelectasis, invasion of the right hilar vessels, and mediastinal lymph node metastasis. Further investigation with MRI detected multiple metastatic lesions in the brain and spinal cord. A bronchoscopic biopsy confirmed small cell lung cancer (SCLC) at the extensive stage.

Initial treatment commenced with two cycles of inductive chemotherapy using etoposide (100 mg/m², days 1–5) and cisplatin (120 mg/m², day 1). This regimen led to a partial response (PR). Concurrent chemoradiotherapy (cCRT) followed, coupled with two more cycles of adjuvant chemotherapy. The radiotherapy targeted the primary lung lesion, right hilar lymph nodes, spinal cord metastases, and brain lesions. Although the patient experienced moderate gastrointestinal side effects (grades 1–2) and severe bone marrow suppression (grade 4), the overall response remained PR.

By October 2018, PET/CT scans showed new multifocal metastases in the right lower lobe and multiple mediastinal lymph nodes, confirmed as progressive disease. A plasma ctDNA test indicated high blood tumor mutational burden (bTMB) at 23.33 muts/Mb. Owing to limited immunotherapy options for SCLC, the patient received two additional cycles of “etoposide + lobaplatin,” which unfortunately did not halt disease progression.

In December 2018, therapy switched to anlotinib (12 mg d1–14/q3w). The tumor soon shrank and showed signs of cavitation. After dose adjustments due to paronychia and later re-escalation, the best recorded efficacy was PR with minimal adverse reactions. In January 2021, durvalumab was added (1,000 mg every 4 weeks) to the anlotinib regimen to further optimize disease control and minimize side effects. The most recent follow-up in March 2022 revealed a bTMB reduction to 0 muts/Mb, suggesting continuous clinical benefit from anlotinib plus durvalumab.