Keytruda (pembrolizumab)

P2, N=32, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center

P2, N=75, Suspended, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Suspended

P1, N=5, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | N=82 --> 5

Although outcomes varied depending on the PEM treatment duration and the medical cost setting after disease progression in the SoC group, PEM was suggested to be more cost-effective than SoC at the reference willingness-to-pay threshold of JPY15 million per QALY in Japan.

P2, N=67, Completed, Washington University School of Medicine | Trial completion date: Dec 2025 --> Jul 2025 | Active, not recruiting --> Completed

P3, N=500, Not yet recruiting, Janssen Research & Development, LLC

P3, N=738, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1/2, N=242, Recruiting, VM Oncology, LLC | Phase classification: P1 --> P1/2 | N=82 --> 242 | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

P2, N=171, Completed, Immutep S.A.S. | Active, not recruiting --> Completed

P1/2, N=161, Completed, Acerta Pharma BV | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Oct 2025

This overview provides a concise synthesis of targeted therapies under investigation or already in clinical use, including monoclonal antibodies against epidermal growth factor receptor (EGFR) (e.g., cetuximab) and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), as well as inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) or agents targeting angiogenic and intracellular signaling pathways such as VEGF and mTOR...Metformin and statins, for instance, have demonstrated anti-proliferative and pro-apoptotic effects in preclinical OSCC models. Notably, recent evidence suggests that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may improve survival specifically in patients with PIK3CA-altered Head and Neck tumors, potentially through modulation of the COX-2/PGE2 axis. Although prospective evidence remains limited and somewhat heterogeneous, existing preclinical and observational studies suggest that these agents may improve survival and reduce treatment-related toxicity, further pointing to the relevance of molecular stratification in guiding future repurposing strategies. This article aims to map the current therapeutic landscape, highlighting both established molecular targets and emerging repositioned drugs in the management of OSCC and OPSCC.

The "immune+/replication+" showed sensitivity to pembrolizumab (OR = 10.192, p < 0.001) and veliparib/carboplatin (OR = 5.184, p = 0.006), while "immune-/replication-" responded poorly to pembrolizumab (OR = 0.086, p < 0.001). Additionally, "immune+/replication-" had the best distant recurrence-free survival (DRFS), whereas "immune-/replication+" had the worst (log-rank p = 6 × 10-4, HR = 5.45). By linking imaging heterogeneity directly to molecular subtypes and therapeutic response, this framework provides a robust, non-invasive surrogate for genomic profiling and a strategic tool for personalized neoadjuvant therapy selection.