Petr Szturz

Presentation
In squamous cell carcinoma of the head and neck (SCCHN), immunotherapy aimed at modulating the immune response was introduced into clinical practice almost a decade ago, with the approval of two anti-programmed cell death-1 (anti-PD-1) agents, nivolumab and pembrolizumab, for platinum-resistant recurrent and/or metastatic (R/M) disease. In addition to these so-called immune checkpoint inhibitors (ICIs), other types of active immunotherapy include anti-tumour vaccines and oncolytic viruses. On the other hand, passive immunotherapy, in which different components of the immune system are administered directly, encompasses monoclonal antibodies targeting tumour antigens, such as cetuximab, an agent already well established in SCCHN before the advent of ICIs, as well as the reinfusion of effector cells through adoptive cell transfer. But getting back to the ICIs, which indeed revolutionized the treatment landscape of R/M-SCCHN, they became the first anticancer drugs capable of achieving durable disease control, reflected in long-term survivorship in about 20-30% of patients. Their toxicity profile is generally less burdensome than that of traditional chemotherapy, although class-specific immune-related adverse events may have severe consequences if not promptly recognized and managed. The success story of immunotherapy in SCCHN is marked by the approval of ICIs in both the first- and second-line settings. However, their integration into locoregionally advanced (LA) disease has been challenging. While the combination of ICIs with definitive radiotherapy or chemoradiotherapy has failed to improve efficacy outcomes, recent data from perioperative studies, including those evaluating neoadjuvant immunotherapy and postoperative immunoradiotherapy with or without chemotherapy (Keynote-689) or postoperative immunochemoradiotherapy (NIVOPOSTOP), are expected to change practice. Switching the clinical setting, using ICIs as adjuncts to other modalities, or both at the same time, thus represents a feasible strategy to advance this field forward. Another option, facilitated by the approval of ICIs as single agents even in the first-line setting, is to combine them with novel targeted drugs, an approach already investigated in phase II or III trials. This has been the case for different drug classes involving inhibitors of other immune checkpoints, cytokines, tumour-cell receptors and enzymes, as well as other agents such as engineered cytokines and agonists of co-stimulatory T-cell receptors. Notable attention has been given to multispecific antibodies and immunogenic fusion proteins, some of which are currently in phase III development following encouraging results from earlier-phase studies reporting high overall response rates. Leveraging the innate immune system, employing vaccines and oncolytic viruses, and exploring antibody-drug conjugates nearly complete the list of various investigational approaches. One area that remains to be addressed is cell therapy. Adoptive cell transfer with chimeric antigen receptor (CAR) T-cells has already been standardized in several hematologic malignancies; however, progress in solid tumours has been slow, with only sporadic preclinical or early clinical reports in SCCHN. This is largely due to challenging tumour-specific factors such as a non-permissive tumour microenvironment and tumour antigen heterogeneity. Some of these shortcomings may be overcome through alternative methods of adoptive cell transfer, comprising tumour-infiltrating lymphocyte (TIL) therapy and T-cell receptor (TCR) engineered T-cell therapy, which will also be discussed in the presentation.

Bio
Petr Szturz is a medical oncologist at Lausanne University Hospital in Switzerland, where he oversees an outpatient immuno-oncology Phase I unit and leads the medical oncology program for head and neck cancer. He has served as a principal investigator in clinical trials ranging from early to late stages of development. Dr. Szturz has contributed to over 160 scientific publications and has been actively involved in editorial work and teaching. He has also collaborated with Professor Vermorken on THNO activities for nearly 10 years.