Cisplatin (Cis), continuous infusion 5FU and Cetuximab (Cet) (EXTREME) first-line treatment extends overall survival (OS) over Cis and 5FU of recurrent/metastatic squamous cell head and neck cancer (RM SCCHN) patients. In EXTREME, Cet has been added to a 2-drug combination, which has never shown superiority over any single drug. In this scenario, we are left with an open question about the significance of adding 1 or 2 drugs to biotherapy. In addition, a significant number of pts are excluded from EXTREME for the high incidence of ≥ G3 adverse events (AEs) (>80%), most of them attributable to 5FU. Paclitaxel (P) is active and safe, both alone and with Cis. We conducted a phase IIb trial comparing a 2-drug Cet-Cis regimen with a 3-drug combination (substituting 5FU with P) in terms of progression-free survival (PFS) and tolerability.
Eligible pts had confirmed untreated R/M SCCHN. Pts were randomized to a 3 vs. a 2-drug combination (Cet + Cis w/o P) with maintenance Cet after 6 cycles. Primary endpoint was PFS; secondary end-points were overall survival (OS), response rate (RR) and toxicity. We assumed a non-inferiority margin of 1.40 as compatible with efficacy.
200 pts were randomized and 191 evaluable. Pt characteristics were balanced in the 2 arms. Inferiority hypothesis was rejected (upper limit of one-sided 90% CI of PFS hazard ratio
A 2-drug Cet and Cis regimen proved to be non-inferior in PFS to a 3-drug combination with Cet, Cis and P. The median OS of both regimens is comparable with the 10.1 mos in EXTREME, while life-threatening toxicity rate appeared reduced. These regimens warrant further investigation as a backbone to immunotherapeutic agents.
Clinical trial identification
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale Tumori Milano
All authors have declared no conflicts of interest.