Acute Toxicity Profile and Early Efficacy Results of De-Escalated, Risk-Directed Post-Operative Adjuvant Therapy for Human Papillomavirus-Positive Oropharynx Squamous-Cell Carcinoma: A Phase 2 Trial.

The primary hypothesis of this multi-arm, non-randomized, phase 2 trial was that weight loss, a quantifiable surrogate of mucositis, would be less during de -escalated postoperative adjuvant cisplatin plus radiation therapy (de -POACRT: cisplatin 100 mg/m2 x1 dose; RT 42 Gy given in standard fractionation of 200 cGy/day) compared to historical POACRT (cisplatin 100 mg/m2 x3 doses; RT 60-66Gy) in patients with human papillomavirus-positive oropharynx squamous-cell carcinoma (HPV+ OPSCC). Patients with operable AJCC 8th Edition clinical stage I-III (excluding T 1-2 N 0 , T 4 , and N 3) HPV+ OPSCC underwent surgery. Risk-directed adjuvant therapy included: de -POACRT for high-risk pathology (positive margin, extra-nodal extension), de –POART (42 Gy) for intermediate-risk pathology (lympho-vascular or peri-neural invasion, ≥2 involved regional lymph nodes, lymph node >3 cm, and T 3 or N 2 pathology), and POACRT for T 4 or N 3 pathology. The primary endpoint was percent weight change from the first to the last day of de -POACRT. We hypothesized a 50% reduction in mean percent weight change (H 1 -3.7% for de -POACRT vs H 0 -7.4% [SD=5.46] for historical POACRT). Assuming a cohort distribution of 3:5:1, a sample of 60 patients would accrue 20 patients to de -POACRT, resulting in a power of 0.80 to detect H 1 using a two-sided test with α 0.05. The generalized estimating equation model with identity link function was used to calculate percent weight change. Key secondary acute toxicity endpoints included mean percent weight change during de -POART and POACRT, and change in serum creatinine and requirement for narcotics in each arm. Efficacy endpoints included relapse and death. We enrolled and treated 54 patients with adjuvant therapy: de -POACRT-20, de -POART-30, and POACRT-4. Mean percent weight change during de -POACRT was -4.89 (SEM 0.69; 95%CI -6.24, -3.54), which is significantly different from historical POACRT (p=0.0003). Mean percent weight change during de -POART was -3.18 (SEM 0.52; 95%CI -4.19, -2.17), and during POACRT was -10.11 (SEM 2.89; 95%CI -15.79, -4.43). In each arm, no significant change in serum creatinine from baseline to six weeks after adjuvant therapy occurred. The proportion of patients taking narcotics six weeks after adjuvant therapy was 40% for de -POACRT, 20% for de -POART, and 75% for POACRT. Median follow-up of all patients was 21.0 months (range 7.4- 32.6). Relapse occurred in 1 patient in each of the de -POACRT and de -POART cohorts and in three patients in the POACRT cohort. Death occurred in no patients in the de -POACRT and de -POART cohorts and in one patient in the POACRT cohort. Among patients with HPV+ OPSCC, the mean percent weight loss during de -POACRT was significantly less than during historical POACRT. [ABSTRACT FROM AUTHOR]