Analysis of Outcomes by Smoking Status in a Phase III Trial of De-Escalated Adjuvant Chemoradiation Therapy in Human Papillomavirus (HPV(+)) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Abstract

<h3>Purpose/Objective(s)</h3> In this study, patients with HPV(+)OPSCC were randomized to de-escalated adjuvant therapy (DART) versus standard of care adjuvant therapy (SOC) and were stratified by smoking < or ≥10 pack-years (pys). We performed a prespecified analysis of oncologic outcomes by treatment arm and smoking history, as patients with any smoking status were trial-eligible. We hypothesized that patients with ≥10 pys smoking history would have similar outcomes to patients with <10 pys. <h3>Materials/Methods</h3> MC1675 inclusion criteria have been previously reported. Smoking history was collected and stratified by < or ≥10 pys. MC1675 had a lead-in safety evaluation whereby the first 10 smokers who were randomized to DART were evaluated for locoregional control with consideration for dose modification pending the locoregional recurrences. Prespecified safety parameters were met and patients with a smoking history were allowed on study. Patients were also stratified on study by extranodal extension (ENE+ vs ENE-). We additionally analyzed outcomes by treatment arm and by ENE+ vs ENE-. Kaplan-Meier curves were constructed for various subgroups and point-estimates for rates of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were calculated. <h3>Results</h3> In total, 194 patients (mean age 59.4 yrs, SD 8.48; 89.2% male) were enrolled, (randomized 2:1, DART: 130, SOC: 64); 139 patients (72%) smoked <10 pys and 55 patients (28%) ≥10 pys. There was no significant difference in 2-year LRC, PFS, or OS for patients with ≥10 pys vs <10 pys (PFS data in Table 1). For patients receiving DART, there was no significant difference in 2-year PFS for patients with ≥10 pys (<i>n</i> = 37) vs <10 pys (<i>n</i> = 93), 88.2% vs 87.4%, <i>p</i> = 0.31). As previously reported, ENE+ patients receiving DART had worse PFS than those receiving SOC. However, amongst those who were ENE+ and treated with DART, 2-year PFS was not significantly different for ≥10 pys vs <10 pys (PFS 77.4% vs 81.2%, respectively; log-rank, <i>p</i> = 0.17). <h3>Conclusion</h3> Patients with ≥10 pys had similar oncologic outcomes to those with <10 pys. Outcomes for patients treated with DART did not differ by smoking history in this prespecified analysis. These results suggest that smoking status alone does not portend worse outcomes with DART compared to SOC and that selected patients with ≥10 pys should be considered eligible for de-escalation protocols.