Phoenix rising from ashes, symbolizing cancer recovery

Hope After Failure: How a Second-Line Treatment Triggered a Dramatic Response in Maxillary Sinus Cancer

Kai Mendoza in Health & Wellness September 2025 • 4 min read.

"Discover how a platinum-based chemotherapy regimen, following the failure of anti-PD1 immunotherapy, led to an unexpected and significant recovery in a patient with squamous cell carcinoma of the maxillary sinus."

Immunotherapy, particularly the use of immune checkpoint inhibitors, has revolutionized the treatment of recurrent squamous cell carcinoma of the head and neck (HNSCC). These inhibitors, which target pathways like PD-1, have demonstrated improved progression-free survival (PFS) and higher response rates compared to traditional chemotherapy. This has brought new hope to patients facing these aggressive cancers.

Emerging research suggests that re-introducing chemotherapy after the failure of anti-programmed death ligand (PD-L) 1 or anti-PD 1 treatment can sometimes lead to surprising and significant responses. While these instances have been primarily observed in pharynx and larynx carcinomas, they highlight the potential for sequential treatment strategies.

Paranasal sinus carcinomas, representing only a small fraction (3%) of all head and neck cancers, are often excluded from major clinical trials. This lack of representation results in a significant information gap regarding optimal treatment approaches for this specific population, especially for maxillary sinus carcinomas, which constitute about 80% of these sinus cancers. This article aims to address that gap.

The Unexpected Turnaround: How Chemotherapy Succeeded Where Immunotherapy Failed

Phoenix rising from ashes, symbolizing cancer recovery

A 52-year-old patient with no prior history of significant illness presented with a challenging case of pT4aN0M0 squamous cell carcinoma in the left maxillary sinus. The initial treatment involved an aggressive approach: maxillectomy (surgical removal of the maxilla), cervical lymph node dissection, and left eye enucleation, all performed in February 2017. To further combat the cancer, the surgery was followed by 70 Gy of radiation therapy combined with cisplatin, a chemotherapy drug.

Despite these efforts, just three months after completing radiation therapy in August 2017, an MRI revealed contrast enhancement in the left pterygo-palatal fossa and the upper surface of the left cavernous sinus, indicating a return of the cancer. By December 2017, another MRI confirmed early local disease progression in these areas. A biopsy verified the relapse, and the tumor was deemed unsuitable for complete surgical removal. Facing limited options, the patient was enrolled in a phase I clinical trial (protocol M15-891) that was designed to test an anti-PD-1 antibody (ABBV-181) for advanced solid tumors.

The patient received intravenous infusions of ABBV-181 every two weeks. However, after only two months (four injections), the treatment appeared to fail. Clinical examination revealed a troubling development: a skin fistula forming near the maxillary sinus. Imaging scans (CT and MRI) confirmed that the locoregional disease was progressing. Facing this setback, doctors turned to a second-line treatment option.

In April 2018, a new chemotherapy regimen was initiated, consisting of cisplatin, 5FU (fluorouracil), and cetuximab. The results were remarkable. The first evaluation, conducted after two months, showed an unexpected and significant clinical and radiological response. The skin lesion had completely healed, and after three courses of chemotherapy, a partial response (PR) was achieved, confirmed by a follow-up MRI after six courses. While the patient experienced some side effects, including cutaneous rash and asthenia, they were manageable. Importantly, the patient was able to discontinue all pain medication.

Implications and Future Directions

This case highlights the complex and often unpredictable nature of cancer treatment. While radical surgery followed by radiotherapy remains the standard approach for SCC-MS, the prognosis for patients remains poor. The dramatic response observed in this case, following the failure of anti-PD1 treatment, suggests that sequential treatment strategies, combining immunotherapy and chemotherapy, warrant further investigation. Prospective clinical trials are needed to explore this approach and potentially improve outcomes for patients with this challenging disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.oraloncology.2018.10.017, Alternate LINK

Title: Dramatic Response After Anti Pd1 Treatment Failure In A Squamous Cell Carcinoma Of The Maxillary Sinus

Subject: Cancer Research

Journal: Oral Oncology

Publisher: Elsevier BV

Authors: Mathieu Larroquette, Charlotte Domblides, Sophie Cousin, Ludovic De Gabory, Charles Dupin, Alain Ravaud, Amaury Daste

Published: 2018-12-01

Everything You Need To Know

How does anti-PD1 immunotherapy work, and why did it fail in the case of maxillary sinus cancer?

Anti-PD1 immunotherapy, such as the drug ABBV-181 used in the described case, works by blocking the PD-1 pathway. This pathway normally acts as a 'brake' on the immune system, preventing it from attacking cancer cells. By blocking PD-1, these immunotherapies unleash the immune system to recognize and destroy cancer cells. However, not all patients respond to anti-PD1 therapy, and resistance can develop over time, as seen in the case of the maxillary sinus cancer patient.

What specific treatments did the patient with maxillary sinus cancer receive, and in what order were they administered?

In this specific case, the patient with squamous cell carcinoma of the maxillary sinus initially underwent aggressive treatment, including maxillectomy, cervical lymph node dissection, left eye enucleation, radiation therapy and cisplatin chemotherapy. When the cancer returned, the patient was enrolled in a clinical trial using the anti-PD-1 antibody ABBV-181. After the failure of ABBV-181, a chemotherapy regimen of cisplatin, 5FU (fluorouracil), and cetuximab was administered, leading to a significant and unexpected response.

What is the significance of platinum-based chemotherapy consisting of cisplatin, 5FU, and cetuximab working after anti-PD1 immunotherapy failed?

The case underscores the potential of using chemotherapy after immunotherapy failure, a strategy termed sequential treatment. Specifically, in this case of maxillary sinus cancer, the platinum-based chemotherapy regimen consisting of cisplatin, 5FU, and cetuximab, was effective after the failure of anti-PD1 immunotherapy. This observed response suggests that even after immunotherapy fails, re-introducing chemotherapy can still yield significant results. However, this is not always the case, and further research is needed to identify which patients are most likely to benefit from this approach.

Why are maxillary sinus carcinomas often excluded from major clinical trials, and what impact does this have on treatment strategies?

Paranasal sinus carcinomas, particularly maxillary sinus carcinomas, are relatively rare, accounting for a small percentage of all head and neck cancers. Maxillary sinus carcinomas represent about 80% of these sinus cancers. Due to their rarity, they are often excluded from major clinical trials, leading to a lack of data on optimal treatment strategies. This exclusion makes it difficult to establish standard treatment protocols specifically tailored for these cancers. The absence of dedicated trials contributes to a significant information gap, making cases like this one, where a platinum-based chemotherapy regimen showed success after anti-PD1 immunotherapy failure, all the more valuable.

What are the implications of the patient's response to cisplatin, 5FU, and cetuximab following immunotherapy failure, and what future research is needed?

The success of cisplatin, 5FU, and cetuximab after the failure of anti-PD1 immunotherapy suggests that combining immunotherapy and chemotherapy in sequence could be a promising strategy for treating squamous cell carcinoma of the maxillary sinus. This approach warrants further investigation through prospective clinical trials to determine the optimal sequencing and combination of treatments. Furthermore, research is needed to understand the mechanisms behind this phenomenon and identify biomarkers that can predict which patients are most likely to benefit from sequential therapy.