China
Africa
Explore chapters and articles related to this topic
Immune-Related Adverse Events from Cancer Immunotherapy
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Currently approved ICI targets CTLA-4 and the interaction between PD-1 and its ligand PD-L1. A CTLA-4 inhibitor was first approved for use in metastatic melanoma in 2011 after Dr. Hodi and colleagues’ seminal paper demonstrating superior survival benefits of ipilimumab over standard therapy.1, 4Anti-PD(L)1 antibodies first received approval for use in 2014 following two pivotal clinical trials, KEYNOTE-001 and CheckMate-037, in unresectable metastatic melanoma (NCT01295827, NCT01721746). Since then, ICIs have gained approval for myriad tumor types including, but not limited to, the following: non-small-cell lung cancer, renal cell carcinoma, and head and neck squamous cell carcinoma.5 In fact, a cross-sectional study estimated that 44% of patients diagnosed with cancer in the United States during 2018 were eligible for checkpoint inhibitor therapy.6 Various adverse events were identified through clinical trials as well as retrospective study and research, and those with an immunological mechanism of action were termed immune-related adverse events. Diffuse rashes, fatal colitis, and unusual endocrinopathies, like hypophysitis, were among the first of the irAEs to be appreciated with CTLA-4 antibodies.1, 7–9 Then with the advent of PD-1/PD-L1 blockers, different irAEs surfaced with more cases of pneumonitis and thyroiditis.3, 10–14 However, it was not until Cappelli et al.’s systematic literature review in 2017 that rheumatology-specific irAEs were brought to light.15, 16
Immunotherapy in Head and Neck Cancers
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
There have been initial reports of single-agent activity in patients with relapsed/metastatic disease. For example, trials have used pembrolizumab (an anti-PD1 MAb). In the KEYN0TE-012 trial, patients with PD-L1-positive tumours were divided into HPV+ and HPV− cohorts and were treated with pembrolizumab. Overall, 26 of 51 patients had a reduction in tumour burden. There are several ongoing randomised phase II/III clinical trials with anti-PD1 agents (pembrolizumab, nivolumab, and durvalumab) in patients with relapsed/metastatic disease, and the results are likely to be reported in the next few years. The side effects of immune checkpoint inhibitors are autoimmune adverse reactions, such as skin rash, colitis, hepatitis, and endocrinopathy. In all instances, these treatments require specialist management because they can evolve into serious, even life-threatening, conditions. There is evolving work (both pre-clinical and clinical data) to demonstrate that immune checkpoint inhibition may enhance the effect of, and lead to systemic activity of, a local therapy, such as radiation. These observations, combined with the excitement over the efficacy of single-agent immune checkpoint inhibition, have led to a number of clinical studies that are combining immune checkpoint inhibitors with ionizing radiation.
Selected topics
Published in Henry J. Woodford, Essential Geriatrics, 2022
Targeted therapies interact with specific molecules to prevent the growth or spread of tumours. Examples include monoclonal antibodies directed against the human epidermal growth factor receptor 2 (HER2) for breast cancer, and tyrosine kinase inhibitors to block the growth of metastatic non-small cell lung cancer. Malignant cells have immune system evading mechanisms. Immunotherapies, such as checkpoint inhibitors, can be used to stimulate the immune system or counter immune-suppressing cancer actions. The physiological role of immune checkpoints is to prevent excessive immunity. This can be exploited by cancer cells to escape anti-tumour responses. Checkpoint inhibitors are effective for various malignancies, including some lung and metastatic cancers.36 These newer treatments tend to be tolerated better but do have the potential to cause systemic adverse effects. Chemotherapy-related cognitive impairment is possible and can persist for months to years after completion of treatment.37 It can affect a range of cognitive deficits. It has been detected in 35–60% of women following treatment for breast cancer but is usually only mild in severity. It is more common in older age and in people with pre-existing cognitive decline, making it important to assess cognition prior to chemotherapy. There are few published data on the effects of newer targeted therapies on cognition.
Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer
Published in OncoImmunology, 2023
Tal Flieswasser, Astrid Van den Eynde, Laurie Freire Boullosa, Jöran Melis, Christophe Hermans, Céline Merlin, Ho Wa Lau, Jonas Van Audenaerde, Filip Lardon, Evelien Smits, Patrick Pauwels, Julie Jacobs
Immunotherapy has been integrated as one of the pillars of cancer treatment in many cancer types7. Immune checkpoint inhibitors aim to treat cancer by either activating the immune system or blocking the immunosuppressive tumor microenvironment. Especially, immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown efficacy in a broad range of tumor types, including NSCLC. It should be noted, though, that only a subset of patients responds to single agent treatment, leaving considerable room for improvement8. Inflamed tumors, which have a preexisting CD8+ T cell response to tumor cells, are limited by intra-tumoral PD-L1 expression on those cells and are therefore tackled by antibodies against PD-1/PD-L1. Alternatively, non-inflamed tumors lack the intratumoral cytotoxic T-cells9. A major challenge is how to change a non-inflamed (“cold”) tumor into an inflamed (“hot”) tumor.
Envafolimab – first PD-1/PD-L1 antibody to be administered by subcutaneous injection for microsatellite instability-high or deficient mismatch repair advanced solid tumors
Published in Expert Opinion on Biological Therapy, 2022
Mifen Chen, Mengyun Jiang, Xinhui Wang, Lin Shen, Jian Li
PD-1/PD-L1 inhibitors mobilize the anti-tumor activity of the immune system by blocking the inhibitory effects of the PD-1/PD-L1 signaling pathway in T cells [1]. Currently, several anti-PD-1 and -PD-L1 monoclonal antibodies (mAbs) have been approved for the treatment of various advanced solid tumors, further improving patient survival. However, most of immune checkpoint inhibitors (ICIs) are administered via intravenous infusion, leading to inconvenience and unsatisfactory compliance in patients. As the first subcutaneous PD-L1 inhibitor, envafolimab showed more satisfactory efficacy and safety profiles than other approved PD-1/PD-L1 inhibitors Box 1) [2]. Lastly, ICIs administered via subcutaneous injection may improve the treatment modes for patients with tumors, particularly for those who are in a stable condition and require long-term immunotherapy.
Pembrolizumab as monotherapy in locally advanced cutaneous squamous cell carcinoma
Published in Expert Review of Anticancer Therapy, 2022
The long duration of response to checkpoint inhibitors in several types of cancers, including advanced cSCC, leads to the question ‘how long is treatment necessary?’ While many clinical trials investigating checkpoint inhibitors continue treatment for 2 years, there are numerous examples in clinical practice and the literature of patients having sustained responses after just a few cycles of therapy. A recent article highlights this finding, in which a 92 year old patient with advanced cSCC received 3 cycles of cemiplimab resulting in a CR [45]. The patient subsequently decided to stop treatment, and at 6 months of follow-up remained disease free. Data of checkpoint inhibitor use in the melanoma field may also help answer this question. A single institution observational cohort study of 52 patients that discontinued PD-1 directed treatment after 6–18 months (median 11.1 months) showed 75% of patients remained without disease progression at a medial follow-up of 20.5 months [46]. Although these findings are interesting, additional research is needed to determine the ideal time to discontinue checkpoint inhibitors in responders.