Introduction/Background Non-epithelial ovarian cancers (NEOC) account for less than ten percent of all ovarian carcinomas. The most frequent histological subtype is mature teratomas (MT). This benign tumour can rarely (0.17–2%) degenerate into squamous cell carcinoma (SCC). In this rare clinical setting, no standard of care treatment exists and while early-stage disease can be managed by surgical debulking, advanced and recurrent disease tends to be refractory to established systemic treatments.

Methodology A 39-year-old patient, known for recurrent stage FIGO IC3 SCC associated with a MT NEOC, had a primary R2 surgery, followed by two cycles of carboplatinum-paclitaxel and bevacizumab. Due to rapid progression, the treatment was switched for a second-line gemcitabine bevacizumab association. After two cycles, liver, diaphragmatic and peritoneal progression was detected and a third-line treatment by pembrolizumab was initiated, with no effect after two, three-weekly, cycles. At the admission to our University Center, she suffered from severe right hypochondrial pain. Following multidisciplinary evaluation, cytoreductive surgery was performed. Radiotherapy of the right thoracic wall, the only R1 site, was delayed because of postoperative infectious complications.

Results Four weeks following surgery, a rapid tumour progression was detected in the R1 site and the peritoneum. A personalized treatment by weekly cetuximab at 250 mg/m2 after a loading dose of 400 mg/m2 was initiated, based on a phase II study of cetuximab as monotherapy for unresectable skin’s squamous cell carcinomas. After six weeks of treatment, the patient reported pain reduction in her right abdominal wall and the injected PET-CT confirmed partial tumour response.

Conclusion This report illustrates the anti-tumour effect of cetuximab in this rare and challenging clinical setting. Toxicities were mild, consisting in a grade 1 skin rash treated with doxycycline and sun-avoidance. The patient is currently on cetuximab without signs of disease progression.