In Reply We appreciate comments from Gil-Sierra and colleagues, who highlight important considerations regarding the use of nivolumab plus ipilimumab (N+I) prior to oral cancer surgery,1 including (1) safety and clinical effects leading to consumption of health care resources and (2) appropriate efficacy end points and biomarkers. Safety was a coprimary end point of this study, along with volumetric response. Importantly, the study was not powered to directly compare nivolumab and N+I. With that caveat, as shown in Table 2,1 there were 2 patients in the nivolumab arm and 5 in the N+I arm who manifested at least possibly related grade 3 to 4 adverse events. Two of these events in the N+I arm were infusion reactions that promptly resolved with supportive treatment. If these are removed from consideration, grade 3 to 4 toxic effect rates were 13% (nivolumab arm) and 20% (N+I arm). Median hospital stay was numerically longer in patients receiving N+I (8 days, vs 6 days with nivolumab), but whether this difference is clinically meaningful is questionable. Similarly, although adverse events manifested at numerically earlier time points following N+I, this difference was not statistically significant, and the timing of events did not appear to influence toxic effect severity or resolution with treatment—which were similar in both arms. With the limited numbers of patients in our study, we cannot make broad conclusions regarding safety of N+I in this setting or exclude the possibility that a larger study might identify a more concerning safety profile. However, most importantly and with respect to the safety primary end point, there were no dose-limiting toxic effects or surgical delays following preoperative treatment in either arm.
Schoenfeld JD, Uppaluri R, Haddad RI. Clinical Decision-making About Neoadjuvant Nivolumab Plus Ipilimumab—Reply. JAMA Oncol. 2021;7(2):309–310. doi:10.1001/jamaoncol.2020.6994
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