Neoadjuvant pembrolizumab plus chemotherapy in locally advanced sinonasal carcinoma (NeoPeSino)

PI: Dott. Salvatore Alfieri 

The NeoPeSino study is a clinical trial evaluating the activity of Pembrolizumab in combination with neoadjuvant chemotherapy (i.e., cytoreductive treatment administered before radiotherapy or surgery) and in the adjuvant phase (i.e., after radiotherapy or surgery) in patients with locally advanced sinonasal undifferentiated carcinoma (SNUC). 

The efficacy of neoadjuvant chemotherapy in locally advanced SNUC has already been demonstrated; in this study, it is hypothesized that adding Pembrolizumab to chemotherapy, both as a neoadjuvant agent and in the adjuvant setting, may confirm and enhance the results obtained. 

The study, conducted in accordance with international ethical guidelines, is considered experimental, as the study drug Pembrolizumab has not yet been approved by health authorities for this specific phase of SNUC treatment. However, the potential impact of Pembrolizumab has already been demonstrated in previous clinical trials, supporting the biological and clinical rationale for the use of immune checkpoint inhibitors in this patient setting, with the aim of improving prognosis. 

Enrollment feasibility in the study depends on: patient characteristics (demographics, oncological history, and concomitant diseases), laboratory tests, and radiological parameters, which will be assessed through specific screening examinations prior to treatment initiation. These assessments will follow well-defined timelines. 

Specifically, the trial includes the following eligibility criteria: 

• Histologically confirmed SNUC at a central pathology review, and naïve (i.e., not previously treated) 
• Locally advanced disease, defined as stage III, IVa, or IVb according to the AJCC Cancer Staging Manual, 8th Edition 

The treatment will be conducted as follows: 

1.  In operable SNUC patients: Neoadjuvant Pembrolizumab (administered via intravenous infusion every 3 weeks) combined with chemotherapy (standard treatment with Cisplatin/Carboplatin and Docetaxel) for 3 cycles, followed by surgery (only in resectable cases with an induction chemotherapy response of less than 50%), then concomitant cisplatin with proton therapy (cCPT) * and subsequently adjuvant Pembrolizumab every 3 weeks, for up to one year. 
2.  In inoperable SNUC patients, or in those with an induction chemotherapy response greater than 50%, surgery will be excluded. These patients will first undergo cCPT * followed by adjuvant Pembrolizumab every 3 weeks, for up to one year. 

All therapeutic decisions will be managed through a multidisciplinary discussion for each individual patient. 

At the completion of active treatment, all participants will be monitored by the study physician with follow-up visits and imaging tests to assess for any recurrence of their tumor. 

Patients will also be monitored for adverse effects induced by chemotherapy and radiotherapy, and for potential immune-mediated toxicities caused by immunotherapy, due to hyperactivation of the immune system. In fact, it may happen that Pembrolizumab treatment induces adverse events — mostly known — since the immune system may attack not only diseased cells but also healthy ones it no longer recognizes. In such cases, investigators will propose symptomatic therapies and adopt targeted strategies to reduce the severity of these side effects (e.g., treatment pauses, corticosteroid therapies, etc.). To ensure patient safety regarding toxicities from chemotherapy, radiotherapy, and immunotherapy, participants will be closely monitored. 

Treatment will continue according to protocol and will only be discontinued in the event of disease progression, unacceptable toxicity, or — as always in a clinical trial — based on the decision of the investigator or the patient (who will, however, continue to have access to medical care and will not waive any legal rights or entitled benefits). 

The study team remains available for further information (email: amo@istitutotumori.mi.it). 

* Proton radiation therapy will be performed at the CNAO (National Center for Oncological Hadrontherapy).