Avelumab
Regulatory sources consulted
Approved indications
- Metastatic Merkel cell carcinoma in adults and patients aged 12 years or older.
- Locally advanced or metastatic urothelial carcinoma: maintenance when disease has not progressed after first-line platinum chemotherapy, or after progression during or following platinum or within 12 months of neoadjuvant or adjuvant treatment.
- First-line advanced renal-cell carcinoma, with axitinib.
Clinical warnings
- Major warning · It can cause severe or fatal immune-mediated reactions in any organ. Monitor before and during treatment; withhold for Grade 3 toxicity and discontinue for Grade 4 toxicity, severe recurrence, or inability to taper corticosteroids as specified in the label. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
- Major warning · It can cause serious infusion reactions and severe or fatal complications after allogeneic hematopoietic stem-cell transplantation. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
- Major warning · With axitinib it can cause major cardiovascular events. Permanently discontinue both drugs for Grade 3–4 cardiovascular events. — DailyMed, BAVENCIO set_id 5cd725a1-2fa4-408a-a651-57a7b84b2118
Adverse events
Common (≥1%)
fatigue · musculoskeletal pain · infusion reaction · rash · nausea · constipation · cough · diarrhea · urinary tract infection or decreased appetite in urothelial carcinoma · hypertension, mucositis, palmar-plantar erythrodysesthesia, dysphonia, hypothyroidism, hepatotoxicity, dyspnea, abdominal pain, or headache with axitinib
Rare but serious
severe or fatal immune-mediated reaction · serious infusion reaction · fatal complication after allogeneic transplantation
Pregnancy and lactation
It can cause fetal harm. Verify pregnancy before treatment; use effective contraception during treatment and for 1 month afterward. Do not breastfeed during treatment or for 1 month afterward.
Recent literature (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.