Randomized Phase II Study with Cetuximab in Combination with 5-FU and Cisplatin or Carboplatin Vs. Cetuximab in Combination with Paclitaxel and Carboplatin for Treatment of Patients with Relapsed or Metastatic Squamous Cell Carcinoma of the Head and Neck (CETMET Trial)

SIMPLE SUMMARY: The purpose of the CET-MET trial was to find a new platinum- based chemotherapy regimen in combination with cetuximab for relapsed or metastatic squamous cell carcinoma of the head and neck (RM- SCCHN), that would achieve an equivalent PFS with standard cetuximab and 5-FU/platinum-based chemotherapy (EXTREME regimen), albeit with less toxicity. RM-SCCHN is a disease which affects patients with severe comorbidity and unhealthy life styles, rendering it difficult to treat with toxic regimens such as the EXTREME trial regimen. Immune checkpoint inhibition (ICI) with/or without the addition of chemotherapy has recently been introduced as a first- line treatment option for RM-SCCHN. However, these new treatment options will not be suitable for all patients. The experimental arm of this trial with Cetuximab and paclitaxel/carboplatin is easier to administer and perhaps more beneficial to combine with ICIs due to its favorable toxicity profile and the potential immunomodulatory effects of taxanes. ABSTRACT: Background: Platinum-based chemotherapy with cetuximab is the standard of care for relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN). The aim of this trial was to investigate whether cetuximab and paclitaxel/carboplatin can achieve similar progression-free survival (PFS) with standard cetuximab and 5-FU/platinum-based chemotherapy. Standard chemotherapy treatment for SCCHN is related to severe toxicity and new, less toxic regimens are needed. Methods: In this multicentre, randomized, controlled, phase 2 trial, 85 patients with relapsed or metastatic SCCHN were randomized in a 1:1 ratio to cetuximab and 5-FU/cisplatin or carboplatin (arm A) vs. cetuximab and paclitaxel/carboplatin (arm B). Eligibility criteria included age ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, and adequate organ functions. The primary endpoint was to investigate whether PFS in arm B is significantly worse than PFS in arm A. Results: Median PFS in arm A was 4.37 months (95% CI: 2.9–5.9 m) and 6.5 months (95% CI: 4.8–8.2 m) in arm B, (p = 0.064). Median overall survival (OS) was 8.4 months (95% CI: 5.3–11.5 m) in arm A and 10.2 months (95% CI: 5.4–15 m) in arm B, (HR = 0.71; 95% CI: 0.43–1.16). PFS HR for arm B was not significantly worse than arm A (HR = 0.65; 95% CI: 0.41–1.03). Adverse events ≥ grade 3 were more frequent in arm A than arm B (60% vs. 40%; p = 0.034). Conclusion: Cetuximab and paclitaxel/carboplatin was found to have similar efficacy and less toxicity compared to cetuximab and 5-FU/cisplatin or carboplatin. The experimental arm is easier to administer rendering it a favorable alternative to standard therapy.