Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

[Head and neck cancer : promising results of immunotherapy]. / Cancers de la sphère ORL : l'immunothérapie donne de la voix !

Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC.

L'immunothérapie, en particulier les inhibiteurs de points de contrôles immunitaires (checkpoints) tels que les anticorps anti-PD1 et anti-PDL1, a déjà modifié la prise en charge standard et le pronostic du mélanome, mais également du cancer pulmonaire, rénal et du lymphome de Hodgkin. Les résultats des études préliminaires sont aussi prometteurs dans le traitement des carcinomes épidermoïdes ORL, ainsi que pour des cancers plus rares de la sphère tête et cou, comme les carcinomes nasopharyngés et les carcinomes de haut grade des glandes salivaires. Le traitement anti-PD1 par nivolumab a récemment démontré un bénéfice de survie globale chez les patients présentant un carcinome épidermoïde ORL récidivant et/ou métastatique résistant aux platines dans une étude de phase 3.

Can local radiotherapy and IL-12 synergise to overcome the immunosuppressive tumor microenvironment and allow "in situ tumor vaccination"?

The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8+ T cells that are efficient in killing cancer cells. The key question is: why is this "abscopal effect" so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT. In this case, additional or combinatorial immunotherapy is needed to attenuate these immunosuppressive networks and, therefore, substantially increases the efficacy of RT. Here, we describe a potentially promising synergistic radio-immunotherapy "in situ tumor vaccination" protocol by antagonizing the tumor-immunosuppressive microenvironment with a combinatorial approach using local RT and IL-12-based TH1 response augmentation.

[New drugs at the horizon for men with prostate cancer]. / Quels nouveaux médicaments a l'horizon pour te traitement du cancer avancé de la prostate?

Despite major progress in the understanding of biological mechanisms underlying metastatic prostate cancer, the treatment of men with advanced prostate cancer remains challenging. Several randomized controlled trials with promising or positive results are underway or just released. Here we discuss new treatments which might be used in clinic in the near future: hormonal treatments (Abiraterone and MDV3100), a new chemotherapy (Cabazitaxel), a cellular vaccine (Sipuleucel-T), anti-angiogenic drugs (Bevacizumab, Aflibercept), a new radioactive treatment (Alpharadin) and a new bone-protective agent (Deno-sumab).