Management of recurrent and metastatic oral cavity cancer: Raising the bar a step higher

Oral Oncol. 2020 Feb:101:104492. doi: 10.1016/j.oraloncology.2019.104492. Epub 2019 Dec 11.


In recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN), the armamentarium of systemic anti-cancer modalities continues to grow in parallel with innovations in and better integration of local approaches. The backbone of cytotoxic chemotherapy remains cisplatin with 5-fluorouracil or a taxane. In contrast to cisplatin, the tumoricidal activity of carboplatin monotherapy is debatable. Adding the epidermal growth factor receptor (EGFR) inhibitor cetuximab to a platinum/5-fluorouracil doublet (the so-called EXTREME regimen) produced a statistically but also clinically significant improvement of survival and became thus the standard first-line palliative treatment in adequately fit patients. Interestingly, three large randomized trials (EXTREME, SPECTRUM, and ZALUTE) evaluating different anti-EGFR monoclonal antibodies (cetuximab, panitumumab, and zalutumumab, respectively) demonstrated preferential anti-tumour efficacy in patients with primary cancer in the oral cavity. Modern immunotherapy with immunomodulating antibodies, dubbed immune checkpoint inhibitors, such as anti-programmed cell death protein-1 (anti-PD-1) inhibitors nivolumab and pembrolizumab, showed unprecedented activity in one first-line (KEYNOTE-048) and several second-line trials (CheckMate-141, KEYNOTE-012, KEYNOTE-055, and KEYNOTE-040). In a minority of also heavily-pretreated patients, these agents generate long-lasting responses without the typical chemotherapy-related toxicity, however, at a price of a low overall response rate, rare but potentially life-threatening immune-related adverse events, the risk of hyperprogression, and high costs. In oligometastatic disease, emerging data indicate long-term benefit with locally ablative techniques including metastasectomy and stereotactic radiotherapy of pulmonary but also hepatic and other distant lesions. In the frame of highly-individualized cancer care, a particularly intriguing approach is a combination of systemic and local therapies.

Keywords: Bevacizumab; Buparlisib; Cetuximab; Cisplatin; Epidermal growth factor receptor; Head and neck cancer; Immunotherapy; PI3K/AKT/mTOR pathway; Predictive biomarker; Vascular endothelial growth factor.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Disease Management
  • Humans
  • Molecular Targeted Therapy
  • Mouth / pathology*
  • Mouth Neoplasms / diagnosis*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / therapy*
  • Multimodal Imaging / methods
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Recurrence
  • Treatment Outcome