Table 1
Milestones in the treatment of Locally Advanced Head and Neck Squamous Cell Carcinomas (LA-HNSCC).
| Time | Treatment | Patient benefits | Key references |
|---|---|---|---|
| 2000 | Chemoradiotherapy (CRT) as standard | Better local control and survival (4.5% at 5 years) | Pignon et al., 2000 [3]. |
| 2004 | Postoperative CRT with cisplatin | Improved local control and disease-free survival in high-risk resected HNSCC | Bernier et al., 2004 [55]; Cooper et al., 2004 [56]. |
| 2006 | Altered Fractionated Radiotherapy (AFRT) | Increment of 5-year overall survival rate by 3.4% | Bourhis et al., 2006 [10]. |
| 2006 | Cetuximab with RT | Improved overall survival (45.6% vs. 36.4% at 5 years) | Bonner et al., 2006 [21]. |
| 2007 | TPF (docetaxel, cisplatin, fluorouracil) induction chemotherapy | Improved survival compared to cisplatin and fluorouracil alone | Posner et al., 2007 [16]; Vermorken et al., 2007 [17]. |
| 2012 | Conventional CRT versus accelerated CRT (GORTEC 99-02) | Conventional CRT improved progression-free survival | Bourhis et al., 2012 [14]. |
| 2018 | Cetuximab with CRT versus cetuximab-RT (GORTEC 2007-01) | Better progression-free survival and local control | Tao et al., 2018 [26]. |
| 2018 | TPF induction then cetuximab-RT versus CRT (GORTEC 2007-02) | Reduction of metastatic rate without survival benefit | Geoffrois et al., 2018 [19]. |
| 2020 | Xevinapant with CRT | Better local control (54% vs. 33%) and survival | Sun et al., 2020 [34]. |
| 2023 | Pembrolizumab with RT versus cetuximab-RT (PembroRad GORTEC 2015-01) | Similar locoregional control (59% vs. 60%); lower toxicity with pembrolizumab-RT | Tao et al., 2023 [46]. |
| 2024 | Pembrolizumab with CRT versus placebo (KeyNote-412) | Improved event-free survival (57.4% vs. 52.1% at 3 years, not significant); better outcomes in PD-L1 CPS ≥ 20 | Machiels et al., 2024 [47]. |
| 2024 | Avelumab with cetuximab-RT (REACH GORTEC 2017-01) | Better progression-free survival in cisplatin-unfit patients | Tao et al., 2024 [52]. |
| 2025 | Pembrolizumab before and after surgery (KeyNote-689) | Improved event-free survival and tumor response | Uppaluri, et al. The AACR Annual Meeting 2025. |
| 2025 | Nivolumab after surgery with CRT (NIVOPOSTOP GORTEC 2018-01) | Improved disease-free survival | Bourhis, et al. The ASCO Annual Meeting 2025. |
Abbreviations: AACR, American Association for Cancer Research; ASCO, American Society of Clinical Oncology; CPS, combined positive score; GORTEC in English, Head and Neck Oncology and Radiotherapy Group; REACH (GORTEC 2017-01), randomized, phase III clinical trial evaluating the combination of avelumab, cetuximab, and radiotherapy versus standard of care in patients with locally advanced squamous cell carcinoma of the head and neck; NIVOPOSTOP (GORTEC 2018-01), nivolumab as adjuvant treatment in patients with resected head and neck squamous cell carcinoma at high risk of relapse, added to standard chemoradiotherapy; PD-L1, programmed death-ligand 1.
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