Induction chemotherapy effects on very advanced (T3/T4) human papillomavirus-related oropharyngeal cancer for participation in hypoxia-directed major de-escalation (30 Gy) definitive treatment trial.

6076 Background: De-escalation trials in human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) often exclude patients with very locally advanced disease. We previously demonstrated in a Phase II study that for patients with T1-T2 HPV+OPC that de-escalation to 30Gy of definitive chemoradiation based on lack of hypoxia on 18 F-FMISO (fluoromisonidazole) PET (ROC Study) is associated with excellent outcomes (JNCI 2021; JCO 2024). Here, we hypothesized that induction chemotherapy (ICT) could be used in locally advanced (T3-T4) HPV+OPC to down-stage patients and make them eligible for de-escalation and simultaneously improve tumor hypoxia. Methods: We conducted a pilot study in HPV+ OPC patients with AJCC v7 T3-T4 and/or large volume N2b-N2c-N3 disease (i.e. pts ineligible for ROC Study (NCT03323563)). ICT – carboplatin (AUC2), paclitaxel (90 mg/m2), and cetuximab (250 mg/m2 after 400 mg/m2 loading dose) weekly for 6 weeks. To be eligible for de-escalation (ROC), after ICT, patients needed to be down-staged (<=T2). 18 F-FMISO PET scan done prior to ICT, after ICT, and, if eligible for ROC study, about 2 weeks after start of radiation therapy. If an 18 F-FMISO PET scan showed no hypoxia at any time point, no further scans necessary and patients received 30Gy of radiation therapy with 2 cycles of chemotherapy concurrently. Primary outcome is 2-year local control rate in 20 evaluable patients (description only in this pilot study). This abstract reports only on the outcomes of the ICT portion of the study. Results: 20 patients were accrued 3/2023-12/2023. Median age - 70 years old (46-88); Male – 95%; ECOG PS 0 – 80%. Tumor stage – T3 (70%); T4a (30%); N2b (70%); N2c (30%). All 20 patients had pretreatment hypoxia by 18 F-FMISO. Of the 17 evaluable patients post ICT, 14 (82%) had no hypoxia on post ICT scan (other 3 still receiving ICT). Of 3 patients with hypoxia after ICT, 2 had resolution 2 weeks into radiotherapy, and 1 patient is still pending intra-treatment scan. All 17 evaluable patients had a significant enough of a response anatomically to allow treatment on the ROC Study. All patients to date were able to receive 2 cycles of cisplatin (100 mg/m2) without dose or treatment adjustment. Conclusions: Preliminary results suggest that ICT can allow more advanced tumors (T3/T4), that are typically excluded from de-escalation studies, to be de-escalated and may eliminate tumor hypoxia in a large proportion of cases, but a larger study is needed to confirm these results. Further followup of outcomes (2 year local control rate) is still needed. Clinical trial information: NCT05491512 .