The Treatment of Advanced Thyroid Cancer Using Pemetrexed Monotherapy or with Platinum-Based Chemotherapy

BACKGROUND: Mortality from thyroid cancer is driven by advanced forms of the disease. While second-line therapies have been approved and recognized in thyroid cancer guidelines, development of toxicity and resistance requires addition of salvage treatments. METHODS: This retrospective cohort study evaluates the utility of pemetrexed as single agent or in combination with carboplatin for advanced radioiodine refractory differentiated and anaplastic thyroid cancer (ATC) treated at Memorial Sloan Kettering Cancer Center between December, 2023, and December, 2025. Our primary outcome was best overall response, and secondary outcomes were progression-free survival and disease-specific survival. RESULTS: Twenty-two patients (11 with ATC), 68% females, and 95% with distant metastatic disease, received pemetrexed single agent or in combination with carboplatin as a fourth-line therapy for a median duration of about 5 months. Median time to pemetrexed initiation was 73 months. Partial response (PR) was observed in 6/22 (27%) of all patients and in 5/11 (45%) with non-ATC. Median progression-free survival was 148 days for all tumors and 375 days for patients with non-ATC. One patient with ATC remains on pemetrexed/carboplatin with a PR to therapy. CONCLUSIONS: Pemetrexed single agent or in combination with carboplatin has comparable efficacy to approved second-line therapies for advanced thyroid cancer. Prospective Phase II and III clinical trials are needed to confirm the efficacy of this salvage therapy.