# Mitomycin-C for HPV-Positive and HPV-Negative Platinum-Refractory, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Trial

## TL;DR

This study tested mitomycin-C in head and neck cancer patients and found limited effectiveness in HPV-positive cases and no effect in HPV-negative cases.

## Contribution

The study provides clinical evidence on mitomycin-C's efficacy in HPV-positive and HPV-negative head and neck cancers.

## Key findings

- Mitomycin-C had a 9.1% response rate in HPV-positive patients.
- No responses were observed in HPV-negative patients.
- Common side effects included anemia, fatigue, and thrombocytopenia.

## Abstract

The primary aim of this phase 2 trial was to determine the objective response rate (ORR) with mitomycin-C among patients with human papillomavirus (HPV)-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC). The ORR was 9.1% in cohort A and 0% in cohort B. We concluded that mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC.

Background/Objectives: Functional p53 is critical for anti-tumor activity of mitomycin-C. In wild-type TP53 human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) cell lines, mitomycin-C repressed E6 oncoprotein expression and induced p53, p21, and Bax, resulting in apoptosis. In mutant TP53 HPV-negative SCC cell lines, mitomycin-C was inactive. The primary aim of this trial was to determine the objective response rate (ORR) with mitomycin-C among patients with HPV-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck SCC (RM-HNSCC). Methods: Patients with platinum-refractory RM-HNSCC received mitomycin-C (10 mg/m2 on day one every five weeks) until discontinuation criteria were met. Tumor response was assessed by RECIST1.1. We hypothesized an ORR of ≥30% (H1) with mitomycin-C (vs. H0 ORR of ≤10%). Using a two-stage Simon phase 2 design for each cohort, 2 or more responses among 12 evaluable patients were required to enroll 23 additional patients. H1 was accepted if 6 or more responses occurred among 35 evaluable patients (power 0.90; one-sided α = 0.10). Results: Forty-seven patients were treated with mitomycin-C: 34 in cohort A and 13 in cohort B. Tumor response occurred in 3 of 33 evaluable patients in cohort A (ORR 9.1%, 95%CI: 0–19.4) and in 0 of 12 evaluable patients in cohort B. The duration of tumor responses in cohort A was 2.3, 2.5, and 4.5 months. The most common treatment-related AEs of any grade were anemia (96%), fatigue (62%), and thrombocytopenia (40%). No treatment-related deaths occurred. Conclusions: Mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC.