Induction Nivolumab Before CRT Misses Feasibility Threshold in High-Risk HPV+ OPC

This multicenter, randomized phase II trial (IMMUNEBOOST-HPV) assessed the feasibility and safety of induction nivolumab before standard chemoradiation (CRT) in patients with high-risk, HPV-positive oropharyngeal cancer (OPC). Eligible patients had HPV-positive OPC with either T4 and/or N2/N3 disease or a smoking history >10 pack-years. Between July 2019 and September 2021, 62 patients were randomly assigned 1:2 to receive either standard CRT (70 Gy with cisplatin, control arm, n=20) or two infusions of nivolumab followed by CRT (experimental arm, n=41). The primary endpoint was the rate of patients who received full treatment in due time (FTDT), defined by five criteria including receiving two nivolumab infusions, starting CRT between days 27-37, no radiotherapy break ≥7 days, >95% of prescribed RT dose, and a cisplatin dose ≥200 mg/m². The predefined feasibility threshold required two or fewer patients in the experimental arm to fail FTDT. With a median follow-up of 37.5 months, the primary endpoint was not met because four of 41 patients in the experimental arm received <200 mg/m² of cisplatin. Regarding safety, grade 4 to 5 acute adverse events occurred only in the experimental arm, affecting seven patients. The 2-year cumulative incidence (95% CI) of relapse was 7.3% (1.9 to 18.0) in the experimental arm versus 15.0% (3.6 to 34.0) in the control arm. The authors concluded that induction nivolumab before CRT did not meet the predefined feasibility threshold due to reduced cisplatin dosing after toxicity in 10% of patients. While the relapse incidence was numerically lower in the experimental arm, this finding is exploratory and requires confirmation.

If you have HPV-positive throat cancer that's advanced or you have a significant smoking history, you're at higher risk of the cancer returning after treatment. Doctors wanted to see if adding a drug called nivolumab (an immunotherapy) before the usual combination of chemotherapy and radiation could help. In this trial, 41 patients received two infusions of nivolumab first, while 20 patients went straight to the standard treatment.

The main goal was to see if patients could complete the entire new treatment plan on schedule. The strategy was not considered feasible because 4 out of the 41 patients in the nivolumab group could not receive the full planned dose of their chemotherapy drug, cisplatin, due to side effects. In fact, all of the most severe (grade 4-5) side effects during treatment happened in the group that got nivolumab first, affecting seven patients.

After about three years of follow-up, the cancer came back less often in the group that received nivolumab. The estimated relapse rate at two years was 7.3% for that group, compared to 15.0% for the group that had standard treatment alone. While this difference looks promising, the researchers caution that it's an early finding from a small study and needs to be confirmed in larger trials. The takeaway is that this approach might reduce relapse but comes with a real trade-off in increased side effects.