Table 5.
Trials investigating de-escalation or replacement of chemotherapy and/or radiotherapy in HPV+ OPSCC
| Study | Study cohort | Treatment | Outcomes | Toxicity profile | Ref. |
|---|---|---|---|---|---|
| MC1273 (2019) | 80 patients with ≤10 pack-year smoking history, negative margins; cohort B included patients with extranodal extension |
Cohort A: 30 Gy RT plus docetaxel (15 mg/m2) Cohort B: extranodal extension to 36 Gy |
2-year locoregional tumour control 96.2%, PFS 91.1%, OS 98.7% | Grade ≥3 toxicities before RT in 2.5% of patients, no grade ≥3 toxicities at 1 or 2 years after RT | 196 |
| NCT01530997 (2015) | 43 patients with T0–3 N0–2c M0 disease and a minimal smoking history | 60 Gy IMRT with concurrent cisplatin (30 mg/m2) | 3-year locoregional control 100%, distant MFS 100%, DSS 100% | Grade ≥3 dysphagia in 39%, grade ≥3 mucositis in 35%; chemotherapy-related grade ≥3 toxicities included haematological events (11%), nausea (18%) and vomiting (5%) | 201 |
| Quarterback and Quarterback 2b (2021) | 24 and 65 patients; stage III/IV disease without distant metastases (per AJCC 7th edn staging) | Quarterback: three cycles of induction chemotherapy; responders randomized 2:1 to receive 56 Gy (rdCRT) or 70 Gy (sdCRT) RT with concurrent carboplastin (AUC 1.5) Quarterback 2b: 56/50.4 Gy IMRT | Combined rdCRT arms: 2-year LRC, PFS and OS 87.4%, 84.4% and 90.6% | No therapy-related mortality, minimal long-term consequences (to be reported) | 246 |
| ORATOR (2019) | 68 patients, ≥18 years of age with ECOG PS 0–2, stage T1–2 N0–2 tumours; stratification by p16 status | 70 Gy IMRT with high-dose cisplatin (100 mg/m²) or modified cisplatin, cetuximab or carboplatin, for patients with N1–2 tumours or TORS plus ND with 1 cm margins (± adjuvant CRT) | MDADI score (swallowing-related QOL at 1 year): 86.9 vs 80.1 in the RT vs TORS plus ND groups, respectively. | Grade ≥3 dyspagia in 18% vs 26, grade ≥3 hearing loss in 18% vs 0%, grade ≥3 post-operative haemorhage and bleeding (oral cavity) each in two patients in the TORS plus ND group | 213 |
| ORATOR2 (2021) | 61 patients with stage T1–2 N0–2 (AJCC 8th edn) tumours | De-intensified IMRT (60 Gy ± chemotherapy) vs TORS plus ND (± adjuvant 50 Gy IMRT) | Estimated 2-year OS 100% vs 89.2% in the IMRT vs TORS plus ND arms, respectively | Grade 2–5 toxicities in 67% of patients in the RT arm and 71% in the TORS plus ND arm. Study terminated early owing to treatment-related mortality and unacceptable PFS in the TORS plus ND arm | 247 |
An overview of ongoing trials is provided in Supplementary Information. AUC, area under the curve; AJCC, American Joint Committee on Cancer; CRT, chemoradiotherapy; DSS, disease-specific survival; ECOG, Eastern Co-operative Oncology Group; HPV, human papillomavirus; IMRT, intensity-modulated radiotherapy; LRC, locoregional control; MDADI, MD Anderson Dysphagia Inventory; MFS, metastasis-free survival; ND, neck dissection; OPSCC, oropharyngeal squamous cell carcinoma; QOL, quality of life; PFS, progression-free survival; PS, performance status; rdCRT, reduced-dose chemoradiotherapy; RT, radiotherapy; sdCRT, standard-dose chemoradiotherapy; TORS, transoral robotic surgery.