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.

person Eric Jeffrey Sherman Memorial Sloan Kettering Cancer Center, New York, NY info_outline Eric Jeffrey Sherman, Nadeem Riaz, Lara Dunn, Heiko Schöder, Rick Wray, Ian Ganly, Jay Boyle, Snehal G. Patel, Babak Givi, James Vincent Fetten, Winston Wong, Tony Hung, Anuja Kriplani, Kaveh Zakeri, Daphna Y. Gelblum, Yao Yu, Linda Chen, Achraf Shamseddine, Richard J. Wong, NANCY Y. LEE

Authors person Eric Jeffrey Sherman Memorial Sloan Kettering Cancer Center, New York, NY info_outline Eric Jeffrey Sherman, Nadeem Riaz, Lara Dunn, Heiko Schöder, Rick Wray, Ian Ganly, Jay Boyle, Snehal G. Patel, Babak Givi, James Vincent Fetten, Winston Wong, Tony Hung, Anuja Kriplani, Kaveh Zakeri, Daphna Y. Gelblum, Yao Yu, Linda Chen, Achraf Shamseddine, Richard J. Wong, NANCY Y. LEE Organizations Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding No funding sources reported 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.

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