Durable partial response of pulmonary metastases from primary sublingual gland squamous cell carcinoma after pembrolizumab failure: Salvage therapy with paclitaxel plus cetuximab

Primary squamous cell carcinoma (SCC) of the sublingual gland is an extremely rare salivary gland malignancy with limited treatment options, particularly once distant metastases develop. Immune checkpoint inhibitors (ICIs) such as pembrolizumab have demonstrated efficacy in PD-L1–positive tumors; however, progression after ICI therapy remains a major clinical challenge. An 82-year-old man underwent surgical resection of a primary SCC of the sublingual gland in February 2021. Surgical margins were negative, and no recurrence has been observed at the primary or cervical sites up to the present time in 2025. In August 2021, multiple bilateral pulmonary nodules were detected and diagnosed as pulmonary metastases. Pembrolizumab was initiated in January 2022 and administered for 10 cycles, but CT imaging revealed progressive disease with >20% tumor growth and new lesions. Consequently, paclitaxel plus cetuximab therapy was started in September 2022 and continued until November 2022, when grade 1 interstitial pneumonitis led to discontinuation. CT imaging in October and December 2022 showed marked regression, resulting in a partial response (PR) by RECIST criteria. The PR has been maintained without new lesions or progression through June 2025. This case highlights the potential efficacy of paclitaxel plus cetuximab as salvage therapy after ICI failure in pulmonary metastases of PD-L1–high primary SCC of the sublingual gland, even in elderly patients. • Primary squamous cell carcinoma of the sublingual gland is exceedingly rare. • Pulmonary metastases developed after surgery despite tumor-free margins. • Pembrolizumab monotherapy failed despite high PD-L1 expression (CPS ≥20). • Paclitaxel plus cetuximab achieved a durable partial response lasting over 2 years. • This case highlights a sequential strategy of ICI followed by salvage chemotherapy.