Avelumab
Sources réglementaires consultées
Indications approuvées
- Carcinome métastatique à cellules de Merkel chez l’adulte et à partir de 12 ans.
- Carcinome urothélial localement avancé ou métastatique : entretien en l’absence de progression après chimiothérapie de première ligne au platine, ou après progression pendant ou après le platine ou dans les 12 mois d’un traitement néoadjuvant ou adjuvant.
- Carcinome rénal avancé en première ligne, avec axitinib.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer des réactions immunomédiées sévères ou mortelles dans tout organe. Surveiller avant et pendant le traitement ; suspendre au grade 3 et arrêter au grade 4, en cas de récidive sévère ou d’impossibilité de réduire les corticostéroïdes selon l’information de prescription. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
- Mise en garde majeure · Il peut provoquer des réactions graves à la perfusion et des complications sévères ou mortelles après greffe allogénique de cellules souches hématopoïétiques. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
- Mise en garde majeure · Avec axitinib, il peut provoquer des événements cardiovasculaires majeurs. Arrêter définitivement les deux médicaments en cas d’événement cardiovasculaire de grade 3–4. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
Effets indésirables
Communs (≥1%)
fatigue · douleur musculosquelettique · réaction à la perfusion · éruption cutanée · nausées · constipation · toux · diarrhée · infection urinaire ou diminution de l’appétit dans le carcinome urothélial · hypertension, mucite, érythrodysesthésie palmo-plantaire, dysphonie, hypothyroïdie, hépatotoxicité, dyspnée, douleur abdominale ou céphalées avec axitinib
Rares mais graves
réaction immunomédiée sévère ou mortelle · réaction grave à la perfusion · complication mortelle après greffe allogénique
Grossesse et allaitement
Il peut provoquer une toxicité fœtale. Vérifier la grossesse avant le traitement ; utiliser une contraception efficace pendant le traitement et pendant 1 mois après. Ne pas allaiter pendant le traitement ni pendant 1 mois après.
Bibliographie récente (PubMed)
Immunology-based therapies are emerging as an effective cancer treatment, using the body's immune system to target tumors. Immune checkpoints, which regulate immune responses to prevent tissue damage and autoimmunity, are often exploited by cancer cells to avoid destruction. The discovery of checkpoint proteins like PD-1/PD-L1 and CTLA-4 was pivotal in developing cancer immunotherapy. Immune checkpoint inhibitors (ICIs) have shown great success, with FDA-approved drugs like PD-1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab), PD-L1 inhibitors (Atezolizumab, Durvalumab, Avelumab), and CTLA-4 inhibitors (Ipilimumab, Tremelimumab), alongside LAG-3 inhibitor Relatlimab. Research continues on new checkpoints like TIM-3, VISTA, B7-H3, BTLA, and TIGIT. Biomarkers like PDL-1 expression, tumor mutation burden, interferon-γ presence, microbiome composition, and extracellular matrix characteristics play a crucial role in predicting responses to immunotherapy with checkpoint inhibitors. Despite their effectiveness, not all patients experience the same level of benefit, and organ-specific immune-related adverse events (irAEs) such as rash or itching, colitis, diarrhea, hyperthyroidism, and hypothyroidism may occur. Given the rapid advancements in this field and the variability in patient outcomes, there is an urgent need for a comprehensive review that consolidates the latest findings on immune checkpoint inhibitors, covering their clinical status, biomarkers, resistance mechanisms, strategies to overcome resistance, and associated adverse effects. This review aims to fill this gap by providing an analysis of the current clinical status of ICIs, emerging biomarkers, mechanisms of resistance, strategies to enhance therapeutic efficacy, and assessment of adverse effects. This review is crucial to furthering our understanding of ICIs and optimizing their application in cancer therapy.
The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy.
Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.
The PD-L1/PD-1 signaling pathway is the gold standard for cancer immunotherapy. Therapeutic antibodies targeting PD-1, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), and PD-L1, including atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) have received Food and Drug Administration approval and are currently being used to treat various cancers. Traditionally, PD-L1 is known as an immune checkpoint protein that binds to the PD-1 receptor on its surface to inhibit the activity of T cells, which are the primary effector cells in antitumor immunity. However, it also plays a role in cancer progression, which goes beyond traditional understanding. Here, we highlight the multifaceted mechanisms of action of PD-L1 in cancer cell proliferation, transcriptional regulation, and systemic immune suppression. Moreover, we consider the potential role of PD-L1 in the development and pathogenesis of diseases other than cancer, explore PD-L1-focused therapeutic approaches for these diseases, and assess their clinical relevance. Through this review, we hope to provide deeper insights into the PD-L1/PD-1 signaling pathway and present a broad perspective on potential therapeutic approaches for cancer and other diseases. No information is available on the use of axitinib during breastfeeding. Because axitinib is more than 99% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during axitinib therapy and for 2 weeks after the final dose of therapy. When axitinib is used in combination with avelumab or pembrolizumab, refer to those LactMed records.