Table 2.
Surgical Trials: TORS to Replace Definitive RT
| Study | Treatment Arms | Outcomes | Toxicities |
|---|---|---|---|
| ORATOR 54–56 | SOC def RT 70Gy ± chemo (n=34) | For p16+ subset (88% of pts in both arms): | RT patients had superior (but not clinically meaningful) |
| (Phase II, randomized) | - Chemo for N1–2 (n=23, 68%), HD cis preferred. | 3 yr PFS: 96.3% [76.5–99.5] vs. 93.3% [75.9–98.3], p=0.32 | swallowing-related QOL (p=0.049). |
| Resectable OPC. | VS. | 3 yr OS: 96.3% [76.5–99.5] vs. 90.0% [72.1–96.7], p=0.58 | RT pts had more dry mouth over time (p=0.0491). |
| AJCC7 T1-T2 (≤4 cm), | TORS+ND ± SOC 60Gy PORT ± chemo (n=34) | TORS patients used more nutritional supplements at 3 yrs (p=0.015). | |
| N0-N2, any PYSH. | - PORT for: <2 mm margin, ≥1 LN, +LVI, ≥T3 | ||
| Median FU = 45 months | |||
| ORATOR2 57 | Stratified by PYSH, then 1:1 randomization: | 2 yr PFS: 100% [100–100] vs. 83.5% [60.8–93.7] | 1 yr mean MDADI scores (P = 0.85): |
| (Phase II, randomized) | Reduced def RT 60Gy ± chemo (n=30) | 2 yr OS: 100% [100–100] vs. 89.1% [69.6–96.4] | RT: 85.7 ± 15.6 vs. TORS: 84.7 ± 14.5 |
| p16+ or HPV+ OPC. | - LD cis (40 mg/m2) for LN+ (n=21, 72%) | p-values not reported for OS and PFS comparisons. | |
| AJCC8 T1-T2 (≤4 cm), | VS. | Trial was reported with immature survival outcomes. | N=1 in each arm required a peg, none at 1 year. |
| N0-N2, any PYSH. | TORS + ND ± Reduced PORT 50–60Gy (n=31) | Trial closed to accrual in November 2020 due two treatment- | |
| - 60Gy: +margin or +ECE | related deaths from complications in the TORS arm. | Grade 2–5 toxicities: RT 67% vs. TORS+ND 71% | |
| - 50Gy: <3mm margin, >1 LN, LN > 3cm, LVI, ≥T3 | All 4 PFS events occurred in TORS arm (1 bleed, 1 cervical | -significantly more anorexia and dysgeusia in the RT arm | |
| Median FU = 17 months | osteomyelitis, 1 myocardial infarction, 1 local recurrence). | ||
| Comparativeness Effectiveness Trial/ | TORS + ND +/− 56–66Gy adj CRT | Ongoing, not reported | Ongoing, not reported |
| NCT03691441. (Phase IV) | vs. | ||
| p16+ OPC resectable by TORS. | SOC def CRT 70–72Gy | ||
| AJCC7 T1N2a-c, T2N1–2c, T3N0–2c. | HD cis preferred. | ||
| NECTORS 71–72 | Experimental (n=55): | 5 yr PFS (p=0.03): | Peg-dependence 12 months post-treatment (p < 0.0001): |
| (Phase II) | NAC (cis 75 mg/m2 + doce) → TORS + selective ND | - NAC + S: 96.1% [90.8–100] | 0% NAC+TORS vs. 24.5% CRT |
| p16+ OPC. | - CRT historical cohort: 67.6% [50.7–84.5] | Severe Grade 3+ events: | |
| AJCC7 T1–4N0–2c. | CRT historical cohort (n=145): HD cis + IMRT | Pathologic CR rates: 72% primary and 57% nodal. | 12.7% NAC+TORS vs. 24.6% CRT |
| Median FU 20.4 months. | Only 2 of 55 TORS pts received adj CRT. | ||
| OPTIMA II 73–74 | NAC carbo/nab-pacl/nivolumab x3c → RECIST response: | Among 9 TORS patients, 66.7% had pCR. | 1 patient died during NAC. |
| (Phase II) | De-escalated treatment administered in 84.9%. | ||
| p16+ and HPV+ OPC. | |||
| LR: | LR with ≥50% reduction: | ||
| T1-T2 non-bulky tonsil or well-lateralized BOT ≤3 cm, non- | - TORS+selective ND (n=9) | ||
| bulky N2A-2B with ≤2 non-lower neck LNs measuring ≤5 cm. | - Reduced dose def RT 50Gy(n=28): did not | ||
| HR: | qualify for/refused TORS | ||
| T4, N2C-3, >20 PYSH, or non-HPV16 subtype. |
adj=adjuvant, AJCC7=American Joint Committee on Cancer 7th Edition, AJCC8=American Joint Committee on Cancer 8th Edition, chemo=chemotherapy, cis=cisplatin, CRT=chemoradiation therapy, def=definitive, ECE=extracapsular extension, FU=follow-up, Gy=gray, HD=high-dose, IMRT=intensity-modulated radiation therapy, LD=low-dose, LN=lymph node, LVI=lymophovascular invasion, NAC=neoadjuvant chemotherapy, ND=neck dissection, NS=not significant, OPC= oropharyngeal cancer, OS=overall survival, +=positive, peg=percutaneous endoscopic gastrostomy, PORT=postoperative radiation therapy, PFS=progression-free survival, PYSH=pack-year smoking history, RT=radiation therapy, SOC=standard of care, TORS=transoral robotic surgery, wkly=weekly, wks=weeks, yr=year.