4 research outputs found
Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial
No full textPatients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to = 1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2- BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT0410906
The TIGOS trial: A randomized, double-blind phase 3 trial of atigotatug + nivolumab fixed-dose combination with chemotherapy vs atezolizumab with chemotherapy in patients with 1L extensive-stage small cell lung cancer (ES-SCLC)
No full textNivolumab With or Without Ipilimumab in Pediatric Patients With High-Grade CNS Malignancies: Safety, Efficacy, Biomarker, and Pharmacokinetics: CheckMate 908
No full textBACKGROUND: Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO+ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies. METHODS: Patients (N=166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg+IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts). Secondary endpoints included other efficacy metrics and safety. Exploratory endpoints included pharmacokinetics and biomarker analyses. RESULTS: As of January 13, 2021, median OS (80% CI) was 11.7 (10.3-16.5) and 10.8 (9.1-15.8) months with NIVO and NIVO+IPI, respectively, in newly diagnosed DIPG. Median PFS (80% CI) with NIVO and NIVO+IPI was 1.7 (1.4-2.7) and 1.3 (1.2-1.5) months, respectively, in recurrent/progressive high-grade glioma; 1.4 (1.2-1.4) and 2.8 (1.5-4.5) months in relapsed/resistant medulloblastoma; and 1.4 (1.4-2.6) and 4.6 (1.4-5.4) months in relapsed/resistant ependymoma. In patients with other recurrent/progressive CNS tumors, median PFS (95% CI) was 1.2 (1.1-1.3) and 1.6 (1.3-3.5) months, respectively. Grade 3/4 treatment-related adverse-event rates were 14.1% (NIVO) and 27.2% (NIVO+IPI). NIVO and IPI first-dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor programmed death ligand 1 expression was not associated with survival. CONCLUSIONS: NIVO±IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals
“Why did she love her mother’s so?”: L.E.L. Forging Corinne
No full text在十九世紀上半葉歐洲社會對於童話、民間故事的蒐集益加熱烈，民間傳說甚至被視為國族文化的基礎，特別是有關美人魚的傳說逐漸成為跨文化的神話典型之一。此類傳說由政治寓言的縮影，如法國中古傳奇《梅律欣》，轉型為浪漫個人主體追求的代言，如安徒生的《小美人魚》與斯黛夫人的《蔻琳，義大利》。英國女詩人蘭登將梅律欣半人半魚的混雜身體嫁接在蔻琳的聲音上，企求在文學商品化的時代脈動中，鑄煉自身文學的威信，能與當代女詩人的另一典範，有著?虔敬母親?之稱的賀曼絲並駕齊驅。蘭登的自我定義分為三個階段：第一、在〈即興女詩人〉一詩中，蘭登將女詩人蔻琳的即興表演發揮地淋漓盡致，更利用詩人聲音稍縱即逝的特性，她得以擊破流行文學雜誌與年鑑以視覺為賣點的策略。第二、在〈噴泉仙女〉一詩中，蘭登將市場對女性詩人兜售身體的要求，透過梅律欣身體的三重展演，轉化為對她們文字的珍視。第三、〈蔻琳在米賽納角〉一詩則具體而微地體現蘭登如何巧用視覺機制突顯文字的優勢，為斯黛夫人筆下失去義大利詩歌本真的蔻琳賦予聲音。本論文探討蘭登如何與斯黛夫人與賀曼絲這兩位?文學母親?的詩學遺產較勁，以梅律欣的?混合嫁妝?譬喻自己在十九世紀文學商業化潮流下的掙扎。The early decades of the nineteenth century witnessed a renewed interest in the folklore of the mermaid. This period of intensified nation-building and pursuit of individual spirit gradually shifted the political concerns of the medieval romance, such as in the French legend of M?lusine, to the struggle of Romantic author, such as in Corinne, or Italy (1807) by Germaine de Sta?l. Corinne, an improvisatrice of hybrid origin becomes a model for women writers in the nineteenth century. Their responses can be summed up in the polarized paradigm of the poetess represented by Felicia Dorothea Hemans, “the pious mother,” and Letitia Elizabeth Landon, the pretty verse maker.
Landon’s self-definition as a poetess against the model of Corinne develops in three phases in which she adjusts her alignment with her foremothers and finally finds a way out of the impasse bequeathed by them, namely the overwhelming emphasis on the body. First, in “The Improvisatrice,” Landon exploits Corinne’s performative art to exude the visual confines demanded by the popular periodicals and gift annuals. Second, in “The Fairy of the Fountains,” she adapts the matrilineal legend of M?lusine by crafting the word rather than the body of the Fairy into the crux of transgression. Third, in “Corinne at the Cape of Misena,” Landon uses her translation of Corinne’s last song to reinstate her virtuosity. This paper seeks to delineate the ways in which Landon forges her own authority as a new Corinne by capitalizing on the “mingled dower” of M?lusine
