Primary results from IChoice-02, a phase 2 trial of induction chemoimmunotherapy followed by response-adapted de-escalation of chemoradiation in HPV-associated oropharyngeal cancer.

6071 Background: Despite multiple attempts to de-intensify treatments in HPV-associated oropharyngeal cancer (OPC), data with incorporation of immunotherapy remain scarce. Neoadjuvant platinum-based chemotherapy and anti-PD-1 therapy has shown promising pathological response after radical surgery. In IChoice-02 trial, we evaluated the efficacy of induction chemoimmunotherapy followed by response-adapted de-escalation of radiotherapy and omission of concurrent chemotherapy in HPV-associated OPC. Methods: IChoice-02 trial enrolled T1-2/N1-3M0 (excluding T1N1M0 patients with single and≤3cm lymph node) or T3-4N0-3M0 (UICC/AJCC 8th staging system) HPV+ OPC. Following two cycles of induction toripalimab (240mg), docetaxel (75mg/m2) and cisplatin (75mg/m2) every 3 weeks, patients with deep response (CR or ≥50% PR per RECIST in both oropharynx and nodes) were subjected to de-intensified radiotherapy (60Gy) alone with no concurrent chemotherapy, while those otherwise received standard-dose radiation to 70Gy with two cycles of concurrent cisplatin (80mg/m2 every three weeks). The primary endpoint was 2-year progression-free survival (PFS). Results: 97 patients were enrolled from March 2021 until July 2024, including 44 (45.3%) stage I, 28 (28.9%) stage II and 25 (25.8%) stage III. Following induction chemoimmunotherapy, 60.8% (59/97) achieved radiological deep response. 53/73 (72.6%) of stage I-II and only 6/25 (24%) of stage III patients underwent subsequent de-escalation. With 16.5 months median follow-up, 2/59 patients had loco-regional relapse (both in-field) in the de-escalation arm, and 6/38 in the standard arm experienced treatment failure (3 locoregional, 2 distant and 1 with both). 1-year PFS was 92.9%, 96.1% and 87.8% in the full cohort, de-escalation arm and standard arm, respectively. 1-year overall survival (OS) was all 100%. There were no treatment-related deaths. Unexpectedly, two cases of second primary malignancy (one with intracranial lymphoma and the other with melanoma) were observed within 4 months after treatment completion. Conclusions: Induction toripalimab in combination with platinum-based doublet chemotherapy followed by de-escalation of chemoradiation to lower radiation dose with omitted concurrent chemotherapy yielded outstanding 1-year survival. Long-term survival is awaited with further follow-up. Clinical trial information: NCT04867330 .