Dose and volume de-escalation for HPV-associated oropharyngeal cancer: Long-term follow-up of the OPTIMA trial.

Abstract

6575 Background: Human papilloma virus (HPV) associated oropharyngeal cancer is associated with a favorable prognosis, but standard multimodality treatment is associated with substantial treatment related toxicity. A de-escalation treatment paradigm that optimizes oncologic outcomes while reducing toxicity is needed. We sought to further expound on our published OPTIMA data with long-term follow-up and additional pts subsequently treated using the OPTIMA treatment paradigm. Methods: Long-term follow-up of our institutional de-escalation OPTIMA trial (NCT02258659) and retrospective review of additional patients treated subsequently per OPTIMA outline was performed. Pts were classified as low-risk (LR) (≤T3, ≤N2B, ≤10PYH) or high-risk (HR) (T4, ≥N2c, > 10PYH). Pts received induction chemotherapy (IC) of 3 cycles of dose dense carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (subsequently treated). LR with ≥50% response received low-dose radiotherapy (RT) to 50 Gy. LR with 30-50% response or HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45Gy. All others received full-dose CRT to 75Gy. Results: 108 pts consented and 107 were treated (61 on study; 46 subsequently) from October 2014 through November 2019. 1 pt transferred care post-enrollment. Median follow-up was 36 months (interquartile range 17-45). Median age was 63 years (range 33-84) and 95% were male. 47% were LR and 53% were HR. ≥50% tumor shrinkage occurred in 78/107 (73%) of pts overall, and 37/51 (73%) among LR; 41/56 (73%) among HR. 82% of pts received de-escalated (C)RT. Overall, 94% of pts were alive at last follow-up (98% LR; 89% HR). 3 pts (2 HR and 1 LR) developed disease recurrence (2.7%), with 2 local recurrences and 1 distant recurrence. Likelihood of G-tube placement was 3% in low-dose RT, 35% in intermediate-dose CRT, and 84% in full-dose CRT. Conclusions: IC followed by risk-adapted dose and volume de-escalated treatment for HPV+ oropharyngeal cancer demonstrates excellent oncologic and functional outcomes with long-term follow-up. Supported by Celgene, Alinea benefit supported by Grant Achatz/Nick Kokonas, and National Cancer Institute of the National Institutes of Health (NIH) through Grant Number P30 CA14599. Clinical trial information: NCT02258659 .