Sujet(s)
Anticorps monoclonaux , Humains , Anticorps monoclonaux/effets indésirables , Mâle , Sujet âgé , Adulte d'âge moyen , Femelle , Lésions radiques/étiologie , Antinéoplasiques immunologiques/effets indésirables , Tumeurs du poumon/radiothérapie , Tumeurs du poumon/traitement médicamenteux , Bronchoscopie , Radiothérapie/effets indésirablesSujet(s)
Imagerie d'élasticité tissulaire , Maladie veno-occlusive hépatique , Inotuzumab ozogamicine , Leucémie-lymphome lymphoblastique à précurseurs B et T , Humains , Maladie veno-occlusive hépatique/induit chimiquement , Maladie veno-occlusive hépatique/imagerie diagnostique , Maladie veno-occlusive hépatique/diagnostic , Leucémie-lymphome lymphoblastique à précurseurs B et T/traitement médicamenteux , Leucémie-lymphome lymphoblastique à précurseurs B et T/complications , Inotuzumab ozogamicine/effets indésirables , Inotuzumab ozogamicine/usage thérapeutique , Mâle , Femelle , Adulte d'âge moyen , Facteurs de risque , Adulte , Foie/imagerie diagnostique , Foie/anatomopathologie , Foie/effets des médicaments et des substances chimiques , Appréciation des risques , Sujet âgé , Lésions hépatiques dues aux substances/étiologie , Lésions hépatiques dues aux substances/diagnostic , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutiqueSujet(s)
Antinéoplasiques immunologiques , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Traitement néoadjuvant , Nivolumab , Humains , Antinéoplasiques immunologiques/administration et posologie , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutique , Carcinome pulmonaire non à petites cellules/chirurgie , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Tumeurs du poumon/chirurgie , Tumeurs du poumon/traitement médicamenteux , Nivolumab/administration et posologie , Nivolumab/effets indésirables , Nivolumab/usage thérapeutique , Soins périopératoires , Pneumonectomie/effets indésirables , Pneumonectomie/mortalité , Traitement néoadjuvant/effets indésirables , Traitement néoadjuvant/mortalitéRÉSUMÉ
Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.
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Tumeurs de la tête et du cou , Nivolumab , Carcinome épidermoïde de la tête et du cou , Microenvironnement tumoral , Humains , Microenvironnement tumoral/immunologie , Nivolumab/usage thérapeutique , Nivolumab/effets indésirables , Mâle , Carcinome épidermoïde de la tête et du cou/traitement médicamenteux , Carcinome épidermoïde de la tête et du cou/immunologie , Carcinome épidermoïde de la tête et du cou/génétique , Femelle , Sujet âgé , Adulte d'âge moyen , Tumeurs de la tête et du cou/traitement médicamenteux , Tumeurs de la tête et du cou/immunologie , Tumeurs de la tête et du cou/génétique , Études rétrospectives , Marqueurs biologiques tumoraux/génétique , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirables , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/effets indésirables , Résultat thérapeutique , Adulte , Antigène CD274/génétique , Sujet âgé de 80 ans ou plus , Mutation , Génomique/méthodesRÉSUMÉ
BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.
This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.
Sujet(s)
Anticorps monoclonaux humanisés , Antinéoplasiques immunologiques , Récidive tumorale locale , Tumeurs du col de l'utérus , Humains , Tumeurs du col de l'utérus/traitement médicamenteux , Tumeurs du col de l'utérus/mortalité , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/effets indésirables , Femelle , Récidive tumorale locale/traitement médicamenteux , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutique , Résultat thérapeutique , Survie sans progression , Adulte d'âge moyenRÉSUMÉ
Background: HER-2 positive (+) breast cancer (BC) accounts for 20-25% of BC, it is more aggressive, and it has a lower survival rate. Since the approval of trastuzumab in 1998, other HER-2-targeted therapies such as pertuzumab and trastuzumab emtansine (TDM1) have been introduced, improving patient survival. However, cardiotoxicity is an adverse effect of these treatments. Objective: To estimate the incidence of cardiotoxicity with trastuzumab, trastuzumab/pertuzumab, and TDM1 in women with HER-2 + BC treated over a 6-year period at the Hospital de Clínicas and the Hospital Departamental de Soriano. Material and methods: Observational, descriptive, and retrospective study which included patients with HER-2 + BC treated with trastuzumab, trastuzumab/pertuzumab, or TDM1. Results: 81 patients were included, with a cardiotoxicity incidence of 23.4%. Cardiotoxicity was determined by a > 10% decrease in left ventricular ejection fraction (LVEF) (57.9%) and a LVEF < 50% evident during treatment (42.1%). Only 1 patient presented symptomatic heart failure. 63.1% of those who discontinued treatment due to cardiotoxicity managed to resume it. No relationship was evident between cardiovascular history or the administration regimen and the development of cardiotoxicity. Conclusion: The study showed a cardiotoxicity incidence similar to the international one. Most did not present cardiac toxicity, and if they did, it was asymptomatic and reversible.
Introducción: el cáncer de mama (CM) HER-2 positivo (+) representa el 20-25% de los CM, es más agresivo y tiene menor sobrevida. Desde la aprobación del trastuzumab en 1998, se han introducido otras terapias dirigidas al HER-2 como pertuzumab y trastuzumab emtansina (TDM1), con lo cual ha mejorado la supervivencia de las pacientes. Sin embargo, la cardiotoxicidad representa un efecto adverso de estos tratamientos. Objetivo: estimar la incidencia de cardiotoxicidad con trastuzumab, trastuzumab/pertuzumab y TDM1 en mujeres con CM HER-2 +, tratadas en un periodo de 6 años en el Hospital de Clínicas y el Hospital Departamental de Soriano. Material y métodos: estudio observacional, descriptivo y retrospectivo que incluyó pacientes con CM HER-2 +, tratadas con trastuzumab, trastuzumab/pertuzumab o TDM1. Resultados: se incluyeron 81 pacientes. La incidencia de cardiotoxicidad fue del 23.4%. La cardiotoxicidad se determinó por una disminución > 10% de la fracción de ejección del venticulo izquierdo (FEVI) (57.9%) y por una FEVI < 50%, evidenciada durante el tratamiento (42.1%). Únicamente una paciente presentó insuficiencia cardiaca sintomática. El 63.1% de quienes suspendieron el tratamiento por cardiotoxicidad logró reanudarlo. No se evidenció una relación entre los antecedentes cardiovasculares ni con el esquema de administración y el desarrollo de cardiotoxicidad. Conclusión: el estudio mostró una incidencia de cardiotoxicidad similar a la internacional. La mayoría no tuvo toxicidad cardiaca y si la hubo fue asintomática y reversible.
Sujet(s)
Ado-trastuzumab emtansine , Anticorps monoclonaux humanisés , Tumeurs du sein , Cardiotoxicité , Récepteur ErbB-2 , Trastuzumab , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Études rétrospectives , Cardiotoxicité/étiologie , Adulte d'âge moyen , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/antagonistes et inhibiteurs , Trastuzumab/effets indésirables , Anticorps monoclonaux humanisés/effets indésirables , Anticorps monoclonaux humanisés/usage thérapeutique , Sujet âgé , Adulte , Ado-trastuzumab emtansine/effets indésirables , Antinéoplasiques immunologiques/effets indésirables , Incidence , Maitansine/analogues et dérivés , Maitansine/effets indésirablesSujet(s)
Tumeurs du poumon , Nivolumab , Humains , Nivolumab/usage thérapeutique , Tumeurs du poumon/chirurgie , Tumeurs du poumon/traitement médicamenteux , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirables , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/chirurgie , Inhibiteurs de points de contrôle immunitaires/usage thérapeutiqueSujet(s)
Tumeurs du poumon , Nivolumab , Humains , Nivolumab/usage thérapeutique , Tumeurs du poumon/chirurgie , Tumeurs du poumon/traitement médicamenteux , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirables , Carcinome pulmonaire non à petites cellules/chirurgie , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Soins périopératoiresRÉSUMÉ
Libtayo® (cemiplimab-rwlc) injection for intravenous use was recently approved by the US Food and Drug Administration (FDA) for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC), both being the advanced stages of BCC. In the past, it was approved by the FDA for the treatment of metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC), both being the advanced stages of CSCC. Cemiplimab is a monoclonal antibody that works by blocking the programmed death-1 pathway. In two open-label, single-arm, phase 2 studies, cemiplimab was investigated for the treatment of advanced stages of BCC (study 1620, NCT03132636) and advanced stages of CSCC (study 1540, NCT02760498). The primary endpoint was objec-tive response rate (ORR) per independent central review. In the study 1620, both mBCC and laBCC received cemiplimab 350 mg every 3 weeks. ORR was 21% (6/28) and 31% (26/84) in the mBCC and laBCC groups, respectively. In the study 1520, mCSCC was divided into two groups: one receiving cemiplimab 350 mg every 3 weeks (Q3W) and another receiving 3-mg/kg cemiplimab every 2 weeks (Q2W); the third group, laCSCC, received cemiplimab 3 mg/kg every 2 weeks. ORR was 41% (23/56) in the Q3W group, 49% (29/59) in the Q2W group, and 44% (34/78) in the laCSCC group. An acceptable safety profile and antitumor activity was discovered in patients treated with cemiplimab. The recommended dosage for cemiplimab to treat advanced stages of BCC and CSCC is 350 mg every 3 weeks administered intravenously over 30 min.
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Anticorps monoclonaux humanisés , Carcinome basocellulaire , Carcinome épidermoïde , Tumeurs cutanées , Humains , Anticorps monoclonaux humanisés/administration et posologie , Anticorps monoclonaux humanisés/effets indésirables , Anticorps monoclonaux humanisés/usage thérapeutique , Tumeurs cutanées/traitement médicamenteux , Tumeurs cutanées/anatomopathologie , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Carcinome basocellulaire/traitement médicamenteux , Antinéoplasiques immunologiques/administration et posologie , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutique , Injections veineuses , Femelle , Mâle , Adulte d'âge moyenRÉSUMÉ
BACKGROUND: Adverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients. CASE PRESENTATION: We reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy. RESULTS: The median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports. CONCLUSION: Based on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.
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Insuffisance surrénale , Anticorps monoclonaux humanisés , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Anticorps monoclonaux humanisés/effets indésirables , Anticorps monoclonaux humanisés/usage thérapeutique , Tumeurs du poumon/traitement médicamenteux , Adulte d'âge moyen , Mâle , Insuffisance surrénale/induit chimiquement , Femelle , Immunothérapie/effets indésirables , Axe hypophyso-surrénalien/effets des médicaments et des substances chimiques , Antinéoplasiques immunologiques/effets indésirables , Études rétrospectives , Sujet âgé , Hormone corticotropeRÉSUMÉ
Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.
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Tumeurs , Humains , Tumeurs/traitement médicamenteux , Tumeurs/immunologie , Anticorps bispécifiques/effets indésirables , Anticorps bispécifiques/usage thérapeutique , Immunothérapie/effets indésirables , Immunothérapie/méthodes , Animaux , Anticorps monoclonaux/usage thérapeutique , Anticorps monoclonaux/effets indésirables , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutiqueRÉSUMÉ
Systemic capillary leak syndrome (SCLS) is a rare and life-threatening disorder characterised by leaking of intravascular fluid to extravascular tissues. An association with immunotherapy and COVID-19 vaccination has been reported as potential triggers. A case of a patient in her 70s developing SCLS after the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination with a history of metastatic melanoma treated with nivolumab (PD-1 monoclonal antibody) and ipilimumab (anti-CTLA4 monoclonal antibody) is reported. The aetiology and management of SCLS are also reviewed in this case context.
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COVID-19 , Syndrome de fuite capillaire , Ipilimumab , Mélanome , Nivolumab , Humains , Mélanome/traitement médicamenteux , Syndrome de fuite capillaire/induit chimiquement , Nivolumab/effets indésirables , Femelle , Ipilimumab/effets indésirables , Sujet âgé , COVID-19/complications , Vaccins contre la COVID-19/effets indésirables , Vaccin BNT162/effets indésirables , SARS-CoV-2 , Immunothérapie/effets indésirables , Immunothérapie/méthodes , Tumeurs cutanées/traitement médicamenteux , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutiqueRÉSUMÉ
OBJECTIVE: This systematic review aimed to compare the efficacy and safety of regorafenib and nivolumab, two FDA-approved second-line treatments for unresectable Hepatocellular Carcinoma (HCC). METHODS: Literature comparing the efficacy and safety of regorafenib and nivolumab in unresectable HCC patients was systematically searched across seven databases, including: PubMed, SCOPUS, Cochrane Database of Systematic Reviews, ScienceDirect, EBSCOhost, EMBASE, and ProQuest, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was done on April 2nd, 2023. Study quality and risk of bias were assessed using the Agency for Healthcare Research and Quality (AHRQ) and ROBINS-1 tools. The selected studies were included in the qualitative data synthesis. RESULTS: Three trials found that HCC patients taking nivolumab had statistically insignificantly longer OS, TTP, and progression-free survival than those on regorafenib. Nivolumab increased ORR, with largely partial responses, and mixed DCR, with little statistical significance. All three studies showed that nivolumab had fewer side effects and improved tolerance. DISCUSSION: Three retrospective cohort studies with a total of 383 regorafenib-receiving cohorts and 230 nivolumab-receiving cohorts were included in the qualitative analysis. Nivolumab was found to be superior in regards of longer overall survival, longer time to progression, higher objective response rate, and lower adverse event occurrence. However, statistical significance was not achieved in most of the parameters. CONCLUSIONS: The use of nivolumab is preferable as the second-line systemic therapy for unresectable HCC. More high-quality studies are urgently needed to generate quantitative analysis, and to encourage the formation of guidelines for second-line systemic therapy.
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Carcinome hépatocellulaire , Tumeurs du foie , Nivolumab , Phénylurées , Pyridines , Humains , Tumeurs du foie/traitement médicamenteux , Carcinome hépatocellulaire/traitement médicamenteux , Nivolumab/usage thérapeutique , Nivolumab/effets indésirables , Pyridines/usage thérapeutique , Pyridines/effets indésirables , Phénylurées/usage thérapeutique , Phénylurées/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirablesRÉSUMÉ
RATIONALE: Bevacizumab (Bev) is a humanized monoclonal antibody that targets vascular endothelial growth factor A and is primarily used for the treatment of various solid tumors. Aortic dissection (AD) is a severe vascular disease caused by the tearing of the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of different layers of the aortic wall. However, the pathogenesis is not fully understood. Some studies have suggested that Bev treatment is associated with the occurrence of AD. PATIENT CONCERNS: A 67-year-old Chinese male was diagnosed with rectal cancer accompanied by liver and lung metastasis. Three days after starting combined chemotherapy with Bev, the patient developed persistent abdominal pain. Abdominal CT scan revealed celiac trunk AD in the abdominal aorta. DIAGNOSES: The patient was diagnosed with rectal cancer accompanied by liver and lung metastases. Abdominal CT tomography revealed a celiac trunk AD. INTERVENTIONS: Somatostatin combined with valsartan was used to control blood pressure. The patient was subsequently referred for vascular surgery and underwent an abdominal aortic angiography. Conservative treatment was continued. OUTCOMES: Three months after the initiation of treatment, follow-up abdominal CT scans showed stability in the condition of celiac trunk AD, with no abdominal pain or hypertension. There were no signs of worsening dissection, aneurysm formation, or inadequate perfusion of end organs. LESSONS: There may be a connection between Bev and elevated blood pressure as well as celiac trunk AD.
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, Bévacizumab , Tronc coeliaque , Tumeurs du rectum , Humains , Mâle , Tumeurs du rectum/traitement médicamenteux , Tumeurs du rectum/anatomopathologie , Bévacizumab/effets indésirables , Bévacizumab/usage thérapeutique , Sujet âgé , Tronc coeliaque/imagerie diagnostique , /induit chimiquement , Antinéoplasiques immunologiques/effets indésirables , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/secondaire , Tumeurs du foie/secondaire , Tumeurs du foie/traitement médicamenteuxRÉSUMÉ
Triple-negative breast cancer (TNBC) represents a challenging malignancy with limited treatment options and a poor prognosis. Adjuvant therapies, including chemotherapy and immune checkpoint inhibitors (ICI), are commonly employed following breast conservation surgery. However, these treatments can lead to various adverse effects, including cutaneous complications and connective tissue disorders. Here, we present the case of a 54-year-old woman with TNBC who developed morphea, a form of localized scleroderma, following adjuvant chemotherapy and pembrolizumab administration. This case highlights the rarity of drug-induced morphea and emphasizes the importance of recognizing and managing such adverse events in breast cancer patients. We discuss the clinical characteristics, diagnostic challenges, and treatment considerations associated with drug-induced scleroderma-like lesions, as well as the potential mechanisms underlying their development. Furthermore, we review the literature on the incidence, clinical features, and outcomes of scleroderma-like lesions induced by chemotherapy and ICIs. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immunotherapy, as well as the importance of individualized treatment approaches to optimize patient care and outcomes.
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Anticorps monoclonaux humanisés , Humains , Femelle , Adulte d'âge moyen , Anticorps monoclonaux humanisés/effets indésirables , Anticorps monoclonaux humanisés/usage thérapeutique , Tumeurs du sein triple-négatives/traitement médicamenteux , Sclérodermie localisée/induit chimiquement , Antinéoplasiques immunologiques/effets indésirables , Antinéoplasiques immunologiques/usage thérapeutiqueRÉSUMÉ
A 61-year-old man presented to our hospital with a chief complaint of chronic cough. He was diagnosed with lung squamous cell carcinoma at clinical stage cT2aN3M1a. He received chemotherapy up to the fourth line, but both the primary tumor and lymph node metastases increased in size. Nivolumab, administered as the fifth line, resulted in a complete response (CR) that continued for 2 years and 8 months. Treatment was stopped due to the appearance of common terminology criteria for adverse events grade 1 pneumonitis. He was followed up without treatment for 3 years and 8 months, but a left supraclavicular fossa lymph node metastasis appeared. Retreatment with nivolumab was initiated, and the patient achieved CR again. One year and 6 months after retreatment, CR was maintained with nivolumab. This case represents a rare instance in which nivolumab yielded a significant response after a prolonged immune checkpoint inhibitor (ICI)-free interval. Our experience has shown that the long-term response to ICIs may deteriorate in the future. Therefore, retreatment with ICIs may be effective when the initial therapy is successful.
Sujet(s)
Carcinome épidermoïde , Tumeurs du poumon , Nivolumab , Humains , Nivolumab/usage thérapeutique , Nivolumab/effets indésirables , Mâle , Adulte d'âge moyen , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/anatomopathologie , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/effets indésirables , Reprise du traitementRÉSUMÉ
INTRODUCTION: Antibody-drug conjugates (ADCs) represent a revolutionary approach in the systemic treatment for both solid and hematologic tumors. Constituted by an antibody, a cytotoxic payload, and a linker, ADCs aim to selectively deliver cytotoxic agents to tumors while sparing normal tissues. Various ADCs have been tested and approved for multiple solid tumors so far, but if there is one that had a major impact on clinical practice, this is Trastuzumab-deruxtecan (T-DXd). Notably, T-DXd was approved for HER2-positive and HER2-low metastatic breast cancer (MBC), HER2-positive gastric cancer (GC), HER2-mutant non-small cell lung cancer (NSCLC) and HER2 3+ solid tumors. Moreover, it received Breakthrough Therapy Designation for HER2-positive colorectal cancer (CRC). AREAS COVERED: We review preclinical and clinical data of T-DXd, focusing on early-phase ongoing trials exploring combination therapies to enhance the activity of T-DXd in HER2-expressing solid tumors. EXPERT OPINION: The clinical use of T-DXd still raises questions about selection of patients, treatment duration, prioritization over other approved ADCs, and management of resistance. Concerns regarding the toxicity of T-DXd remain, particularly with combinations involving potentially toxic drugs. Advancements in biomarker identification and combination therapies offer promising avenues to enhance efficacy and overcome resistance to T-DXd, ultimately improving outcomes for patients with cancer.