Effectiveness of Cisplatin in P16+ Oropharyngeal Cancer According to Relative Risk for Cancer Events: Ancillary Analysis of RTOG 1016

Abstract

To test the hypothesis that the effectiveness of cisplatin in p16+ oropharyngeal squamous cell carcinoma (OPSCC) increases with patients' relative risk for cancer events. Ancillary analysis of 805 patients enrolled on RTOG 1016 accessed via Project DataSphere. Eligible patients had p16+ OPSCC, AJCC 7th T1-T2 N2a-N3 or T3-T4 N0-N3 M0, ECOG PS 0-1. Patients were randomized to RT with concurrent cisplatin vs. cetuximab. Relative risk for competing events was quantified using the Head and Neck Cancer Intergroup predictive classifier (omega score). Higher scores indicate higher relative risk for cancer events (LRF or distant metastasis) vs. competing mortality. We compared this to favorable, unfavorable/low, and unfavorable/intermediate risk groups using standard criteria: NRG HN005 eligible/low RTOG risk (Ang et al.), HN005 ineligible/low RTOG risk, and intermediate RTOG risk. Omega score cutoffs were selected to match numbers in standard risk strata. HRs for the effect of cisplatin vs. cetuximab on PFS and OS were compared for standard vs. relative risk strata. 1-tailed interaction tests were used to test whether cisplatin effectiveness increased within risk strata. There were 354, 219, and 232 patients in standard favorable, unfavorable/low, and unfavorable/intermediate risk groups. Omega score cutoffs were 0.80 and 0.84 to define low, intermediate, and high relative risk groups. Discordant standard vs. relative risk classifications occurred in 559 patients (69.4%). Increasing omega score was associated with significantly higher relative HR (rHR) for cancer events (3.40, 95% CI: 1.66-6.96) and increasing effectiveness of cisplatin vs. cetuximab (Table), but standard risk grouping was not (rHR 0.80, 95% CI: 0.49-1.32). The effect of cisplatin on PFS significantly increased with higher omega score (interaction -0.30, p = .046), but decreased with increasing standard risk strata (interaction +0.27, p = NS). The effectiveness of cisplatin in p16+ OPSCC increased with higher omega score but not with standard risk group. Relative risk for cancer events should be taken into account when designing deintensification strategies.