PURPOSE: Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung cancer. Treatments are limited for other HER2-expressing solid tumors. METHODS: This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS). RESULTS: At primary analysis, 267 patients received treatment across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. The median follow-up was 12.75 months. In all patients, the ORR was 37.1% (n = 99; [95% CI, 31.3 to 43.2]), with responses in all cohorts; the median DOR was 11.3 months (95% CI, 9.6 to 17.8); the median PFS was 6.9 months (95% CI, 5.6 to 8.0); and the median OS was 13.4 months (95% CI, 11.9 to 15.5). In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6). Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths. CONCLUSION: Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors.
- MeSH
- humanizované monoklonální protilátky škodlivé účinky MeSH
- imunokonjugáty * škodlivé účinky MeSH
- intersticiální plicní nemoci * chemicky indukované farmakoterapie MeSH
- lidé MeSH
- nádory plic * farmakoterapie MeSH
- nádory prsu * farmakoterapie MeSH
- nemalobuněčný karcinom plic * farmakoterapie MeSH
- receptor erbB-2 metabolismus MeSH
- trastuzumab škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
Guselkumab je první inhibitor IL-23 registrovaný pro léčbu psoriatické artritidy (PsA). Interleukin-23 hraje klíčovou úlohu při vzniku psoriázy i psoriatické artritidy. Guselkumab je již schválený pro léčbu ložiskové psoriázy a několik klinických studií prokázalo jeho účinnost i u aktivní PsA – u různých forem onemocnění a různých typů pacientů (po selhání standardní léčby, po selhání léčby inhibitory TNF-α i u pacientů dosud biologicky neléčených). Jeho účinnost na artritidu je minimálně srovnatelná s ostatními biologiky (přímá srovnávací studie však zatím chybí), jeho účinek na kožní projevy psoriázy je mohutný a patrně vyšší než u ostatních biologik. Léčba může být provázena nežádoucími účinky, jako jsou infekce horních cest dýchacích, postinjekční reakce, celkové alergické reakce aj. Oportunní infekce a tuberkulóza při léčbě guselkumabem pozorovány nebyly. Guselkumab se podává subkutánně v dávce 100 mg v 0. a 4. týdnu a dále každých 8 týdnů.
Guselkumab is the first IL-23 inhibitor registered for the treatment of psoriatic arthritis (PsA). Interleukin-23 plays a key role in both psoriasis and psoriatic arthritis. Guselkumab is already approved for the treatment of plaque localized psoriasis and several clinical trials have demonstrated its efficacy in active PsA – in different forms of the disease and in different types of patients (after failure of standard treatment, after failure of TNF-α inhibitor treatment as well as in patients not yet biologically treated). Its efficacy on arthritis is at least comparable to other biologics (however, a direct comparative study is still lacking), its effect on the cutaneous manifestations of psoriasis is robust and probably higher than that of other biologics. Treatment may be accompanied by side effects such as upper respiratory tract infections, post-injection reactions, general allergic reactions, etc. Opportunistic infections and tuberculosis have not been observed during the treatment with guselkumab. Guselkumab is administered subcutaneously at a dose of 100 mg at weeks 0, 4 and every 8 weeks thereafter.
- Klíčová slova
- guselkumab,
- MeSH
- hodnocení léčiv MeSH
- humanizované monoklonální protilátky škodlivé účinky terapeutické užití MeSH
- interleukin-23 - podjednotka p19 antagonisté a inhibitory MeSH
- lidé MeSH
- psoriatická artritida * farmakoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- ixekizumab,
- MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- psoriatická artritida * diagnóza farmakoterapie MeSH
- psoriáza * diagnóza farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- secukinumab, studie SUNSHINE, studie SUNRISE,
- MeSH
- hidradenitis suppurativa * farmakoterapie MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakokinetika škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- MeSH
- ankylózující spondylitida farmakoterapie MeSH
- humanizované monoklonální protilátky farmakologie škodlivé účinky terapeutické užití MeSH
- interleukin-17 antagonisté a inhibitory škodlivé účinky terapeutické užití MeSH
- kongresy jako téma MeSH
- lidé MeSH
- nežádoucí účinky léčiv MeSH
- psoriatická artritida * etiologie farmakoterapie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- novinové články MeSH
- zprávy MeSH
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.
- MeSH
- humanizované monoklonální protilátky škodlivé účinky MeSH
- lidé MeSH
- nádory prsu * farmakoterapie genetika MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- receptor erbB-2 MeSH
- trastuzumab škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown. METHODS: In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events. RESULTS: Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. CONCLUSIONS: Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729.).
- MeSH
- antigeny CD3 antagonisté a inhibitory imunologie MeSH
- beta-buňky účinky léků imunologie MeSH
- C-peptid analýza MeSH
- diabetes mellitus 1. typu * diagnóza imunologie terapie MeSH
- dítě MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * škodlivé účinky farmakologie terapeutické užití MeSH
- hypoglykemika aplikace a dávkování terapeutické užití MeSH
- inzulin aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- progrese nemoci MeSH
- T-lymfocyty účinky léků imunologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
The authors present a case of a complete treatment response in a patient treated for metastatic Merkel cell carcinoma with a combination of radiotherapy and immunotherapy with avelumab. Immunotherapy was terminated prematurely due to relapse of myelodysplastic syndrome. Despite premature termination of immunotherapy, complete disease remission has been sustained. Clinical and histopathological properties of Merkel cell carcinoma and the recommended treatment algorithm are discussed. Attention is paid to the management of avelumab treatment.
Autoři prezentují případ kompletní léčebné odpovědi u pacienta léčeného pro metastazující karcinom z Merkelových buněk kombinací radioterapie a imunoterapie avelumabem. Imunoterapie byla předčasně ukončena pro relaps myelodysplastického syndromu. I přes předčasné ukončení imunoterapie trvá obraz kompletní remise onemocnění. Diskutovány jsou klinické a histopatologické vlastnosti karcinomu z Merkelových buněk a doporučený terapeutický algoritmus. Pozornost je věnována managementu léčby avelumabem.
- Klíčová slova
- avelumab,
- MeSH
- humanizované monoklonální protilátky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- imunoterapie metody MeSH
- lichen sclerosus et atrophicus diagnóza etiologie terapie MeSH
- lidé MeSH
- Merkelův nádor * diagnóza patologie terapie MeSH
- myelodysplastické syndromy MeSH
- PET/CT metody MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- radioterapie metody MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- pembrolizumab,
- MeSH
- doxycyklin aplikace a dávkování MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- humanizované monoklonální protilátky farmakologie škodlivé účinky terapeutické užití MeSH
- imunoterapie škodlivé účinky MeSH
- inhibitory kontrolních bodů farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nežádoucí účinky léčiv * farmakoterapie MeSH
- senioři MeSH
- terapie neúspěšná MeSH
- ústní sliznice patologie MeSH
- vředy v ústech * chemicky indukované diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND & AIMS: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. METHODS: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). RESULTS: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. CONCLUSIONS: Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. CLINICALTRIALS: gov number: NCT04033445.
- MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky škodlivé účinky MeSH
- imunosupresiva terapeutické užití MeSH
- indukce remise MeSH
- lidé MeSH
- ulcerózní kolitida * diagnóza farmakoterapie komplikace MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- randomizované kontrolované studie MeSH