Oropharynx cancer (OPC) in TAX 324: Human papillomavirus (HPV) and survival.

Abstract

5525 Background: HPV is an important prognostic and biologic marker in OPC. The association between HPV and survival (OS) in OPC was examined in TAX324, a prospectively randomized, international, phase III trial of sequential therapy (ST) in patients (pts) with locally advanced squamous cell cancer of the head and neck. Methods: The TAX324 trial has been reported (Posner, NEJM, 2007). Accrual was completed in 2003. OS data were collected through 2008. Tissues from untreated OPC tumors were studied by PCR for HPV16. HPV status was linked to long-term OS, progression-free survival (PFS), and demographics. Results: Of 264 evaluable pts with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. Nodal and clinical stages were similar; however, HPV+ pts were significantly more likely to: be younger (54 vs. 58 yrs, p=0.02), be Caucasian (96% vs. 84%, p=0.03), have T1/T2 primary cancers (49% vs. 20%, p=0.001), and have a PS of 0 (77% vs. 49%, p=0.003). Median follow-up period (range) for HPV+ and HPV- pts were 8 3(77-93) and 82 (68-86) months (mo), respectively. OS was significantly better for HPV+ vs. HPV- pts, HR = 0.20 (0.10-0.38, p<0.0001). Median survival time for HPV- pts was 21 mo and not reached for HPV+ pts. Rates of OS and PFS from 1 to 5 yrs were significantly better for HPV+ vs. HPV- pts (Table, p <0.0001 for all comparisons*); at 5 yrs, 82% of HPV+ pts were alive compared to 35% of HPV- pts. There were too few pts to compare differences between TPF and PF in this subset. Conclusions: HPV+OPC has a different biology, demographics, and OS compared to HPV- OPC. Both the OS and PFS obtained with ST at 5 years in HPV+OPC are unprecedented. The excellent PFS predicts durable long-term OS. These data support the notion of developing different therapeutic approaches for HPV+ and HPV- OPC. Our data suggest that it might be possible to reduce long-term morbidity in HPV+OPC and preserve survival by reducing radiotherapy intensity in the context of ST, and that we might best approach HPV- disease with more aggressive ST and/or CRT. OS* HPV+ N=56 HPV- N=55 1-yr 93% (82-97) 69% (54-79) 2-yr 89% (78-95) 48% (34-61) 3-yr 87% (75-94) 41% (28-53) 5-yr 82% (69-90) 35% (23-48) PFS* 1-yr 85% (73-92) 52% (38-64) 2-yr 83% (70-91) 35% (23-48) 3-yr 81% (68-90) 33% (21-46) 5-yr 78% (64-87) 28% (17-40) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis