Non-Inferiority Margin and Nodal Analysis of De-Escalated Adjuvant Radiation Therapy (DART) for HPV-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Preplanned Pooled Analysis of MC1273 & MC1675

Abstract

<h3>Purpose/Objective(s)</h3> We previously reported the results of phase II/III trials (MC1273 & MC1675) evaluating 30-36 Gy of adjuvant radiation therapy for patients with HPV+ OPSCC. Herein we report the results of a pre-planned pooled analysis of MC1273/MC1675 designed to test whether the pooled PFS was statistically non-inferior to the PFS target of NRG HN005. <h3>Materials/Methods</h3> Pts who received DART on MC1675, or pts on MC1273 who fit MC1675 criteria were included in this analysis. All pts underwent margin clearing surgery and neck dissection. Pts with pT4 disease or required >2 attempts to clear margins were excluded. Pts with intermediate risk factors received 30 Gy/1.5 Gy b.i.d. + docetaxel 15 mg/m2 days 1 & 8, while pts with extranodal extension (ENE) simultaneously received 36 Gy/1.8 Gy b.i.d. to ENE+ nodal levels. A pooled analysis was performed on LRC, PFS, and OS using survivorship methodology, including Kaplan-Meier estimation. Pooled 2-yr PFS for the total cohort and subgroups were compared with the PFS non-inferiority margin for HN005 (86.9-92.3%). Cox proportional hazards regression analysis was performed to evaluate the effect of nodal and ENE status on survival outcomes. OS, PFS and LRC were evaluated using Chi-square tests. <h3>Results</h3> Accrual at Mayo Clinic Rochester and Arizona was from 2013 – 2020: MC1273: 72 pts, MC1675/DART: 130 pts, 202 total.) Median follow-up as of 10/21 was 36.6 months. 2 year estimates and 95% CI of OS, LRC, PFS for de-escalated pts can be found in Table 1. The hazard ratios (HR) for ENE status was OS 2.07 (p=0.39); LRC undefined (p=0.99); PFS 3.95 (p=0.015). HR for AJCC 8 pN2 was OS 5.78 (p=0.014), LRC 2.29 (p=0.23), PFS 4.11 (p=0.001). <h3>Conclusion</h3> Pooled PFS for MC1273/1675 (91.1%) was non-inferior to the target PFS for HN005 (92.3%, p = 0.29), and was also significantly above the HN005 acceptable PFS threshold of 86.9% (p=0.043). All ENE/pN subgroups also had PFS significantly above the 86.9% threshold except for the ENE+/pN2 cohort. On multivariate analysis, nodal status was a stronger predictor of OS than ENE. Analyses for extent of ENE and AJCC 7 N stage will be available for the meeting.