Efficacy Of Durvalumab Research Articles

Safety and efficacy of durvalumab following trimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Early efficacy results from Big Ten Cancer Research Consortium study.

5 Background: The standard of care for locally advanced esophageal adenocarcinoma(LA-EAC) is concurrent chemoradiation (CRT) followed by esophagectomy. Approximately 30% of patients (pts) achieve complete pathologic response (pCR) with this approach. The risk of relapse in the remaining 70% of pts is high, with 1-yr relapse free survival (RFS) of 50%. No adjuvant therapies have been shown to improve survival. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown upregulation of PD-1 pathway with radiation +/- chemotherapy. Methods: We conducted a phase II study evaluating safety and efficacy of durvalumab (durva), a monoclonal antibody against PD-L1, in pts with LA-EAC and GE junction (GEJ) adenocarcinoma who do not achieve pCR after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1 yr after surgery. Primary objective was 1-yr RFS. Secondary objectives were incidence and severity of treatment related adverse events (AEs). Results: Twenty-four pts were enrolled from Apr 2016 to Jan 2018 (median age: 60yrs (range, 43-74)). Fourteen pts had GEJ adenocarcinoma and 10 had distal EAC. Eighteen received carboplatin/paclitaxel and six received cisplatin/5-FU concurrently with 50-50.4Gy radiation. Nineteen pts (79%) had positive lymph nodes at the time of surgery after neoadjuvant CRT, including three (12.5%) with N3, nine (37.5%) with N2, and seven (29%) with N1 disease. Among N0 pts, two had T3N0, one had T2N0, and two had T1N0 disease. At median follow-up of 11.7 mo (range 1.7-23.9 mo), seven pts (29%) have relapsed (five alive, two died); 17(67%) are disease free (six on treatment, seven completed treatment, three off-treatment); 1-yr and projected 26 mo RFS are 78.6% and 62.9%, respectively. Five pts (20.8%) developed grade 3 AEs: diarrhea (n = 1), hepatitis (n = 1), encephalopathy (n = 1), hyperglycemia (n = 1), hypoglycemia (n = 1). Most common grade 1 and 2 AEs were fatigue (33.3%), nausea (25.0%), and cough (20.8%). Conclusions: Adjuvant durva in pts with residual disease following trimodality therapy for EAC and GEJ adenocarcinoma is safe and feasible with 1-yr RFS of 78.6% compared to historical rate of 50%. Clinical trial information: NCT02639065.

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC

Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. To assess safety and objective response rate of durvalumab combined with tremelimumab. The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. Safety and tolerability and efficacy measured by objective response rate. Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way. clinicaltrials.gov Identifier: NCT02319044.

1236TiP - The safety and efficacy of durvalumab in combination with paclitaxel for the treatment of metastatic triple negative breast cancer

1236TiP - The safety and efficacy of durvalumab in combination with paclitaxel for the treatment of metastatic triple negative breast cancer

904P - Impact of different programmed cell death ligand-1 (PD-L1) expression algorithms on patient selection and durvalumab efficacy in urothelial carcinoma (UC)

904P - Impact of different programmed cell death ligand-1 (PD-L1) expression algorithms on patient selection and durvalumab efficacy in urothelial carcinoma (UC)

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors.

IntroductionThe prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.MethodsA systematic search of PubMed, Embase, and related articles was performed. Safety data were analyzed using Comprehensive Meta-Analysis software program version 2. Ultimately, 17 studies with 1,529 patients were included in our analysis.ResultsThe major adverse events associated with durvalumab were pruritus and fatigue, while pruritus, increased alanine transaminase, and increased aspartate aminotransferase were common among patients treated with a combination of durvalumab and tremelimumab. Higher PD-L1 expression was associated with a superior objective response rate.ConclusionDurvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved prognosis. PD-L1 expression is a biomarker of the efficacy of durvalumab.

Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal adenocarcinoma: Early results from Big Ten Cancer Research Consortium study.

Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal adenocarcinoma: Early results from Big Ten Cancer Research Consortium study.

Safety and efficacy of durvalumab in combination with tremelimumab, durvalumab monotherapy, and tremelimumab monotherapy in patients with advanced gastric cancer.

4031Background: The combination of durvalumab (D; anti–PD-L1) and tremelimumab (T; anti–CTLA-4) has the potential to amplify T-cell responses against tumors through immune checkpoint blockade, resu...

Reply by Authors

No AccessJournal of UrologyLetter to the Editor/Errata1 Mar 2018Reply by Authors View All Author Informationhttps://doi.org/10.1016/j.juro.2017.09.159AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 199(3), pp. 855–856 References 1 : Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol2015; 26: 812. Google Scholar 2 : Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol2016; 34: 3119. Google Scholar 3 : Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet2016; 387: 1909. Google Scholar 4 : Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol2016; 17: 1590. Google Scholar 5 : PD-L1 expression in melanoma: a quantitative immunohistochemical antibody comparison. Clin Cancer Res2017; 23: 4938. Google Scholar 6 : Comparison of different antibody clones for immunohistochemistry detection of programmed cell death ligand 1 (PD-L1) on non-small cell lung carcinoma. Appl Immunohistochem Mol Morphol2017; 10.1097/PAI.0000000000000531. Crossref, Google Scholar 7 : PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol2017; 12: 208. Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 199Issue 3March 2018Page: 855-856 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC).

4525 Background: Anti-PD-L1 immunotherapy shows promising clinical activity in UC. We report a planned update of the safety and efficacy of durvalumab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. Methods: Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. Primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review (RECIST v1.1). Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Tumor PD-L1 expression was assessed by Ventana SP263 assay (PD-L1 high = ≥25% PD-L1 expression on tumor or immune cells). Results: As of Oct 24, 2016 (data cutoff [DCO]), 191 pts had received treatment. Median follow-up was 5.78 mo (range, 0.4–25.9). All pts had Stage 4 disease and 99.5% had prior anticancer therapy (95.3% post-platinum). As of DCO, ORR was 17.8% (34/191), including 7 CRs, with responses observed regardless of PD-L1 status (Table). Responses occurred early (median time to response, 1.41 mo) and were durable (median DoR not reached [NR]). Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively; the 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%). Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated (im)AEs occurred in 4 pts; 2 pts discontinued due to imAEs (acute kidney injury and autoimmune hepatitis). Conclusions: Durvalumab 10 mg/kg Q2W shows favorable clinical activity and an excellent safety profile in locally advanced/metastatic UC pts. Table. Antitumor activity in UC pts, including second-line or greater (≥2L) post-platinum pts Clinical trial information: NCT01693562. [Table: see text]

O2-8-1 - Safety and efficacy of durvalumab (MEDI4736) plus tremelimumab in advanced non-small-cell lung cancer (NSCLC)

O2-8-1 - Safety and efficacy of durvalumab (MEDI4736) plus tremelimumab in advanced non-small-cell lung cancer (NSCLC)

Abstract IA20: Phase II study to evaluate the clinical efficacy and safety of MEDI4736 (durvalumab) in patients with glioblastoma (GBM): Results for cohort B (durvalumab monotherapy), bevacizumab-naïve patients with recurrent GBM

Abstract Background: Outcome for patients with glioblastoma (GBM), the most common primary malignancy of the central nervous system, remains poor. Inhibition of PD-1 signaling has been shown to improve survival in an orthotopic, syngeneic murine GBM model. PD-L1 is expressed by GBM tumors, and its level of expression has been shown to correlate with patient outcome. Durvalumab (DUR) is a human IgG1 monoclonal antibody against PD-L1. Blockade of PD-1/PD-L1 has shown benefit among solid tumors; data implicate PD-1/PD-L1 signaling as a significant contributor to immunosuppression in glioblastoma (GBM). Bevacizumab (BEV) is an approved angiogenesis inhibitor for recurrent GBM; angiogenesis inhibition may promote antitumor benefit of immunotherapies. Methods: This ongoing phase II open-label study (NCT02336165) evaluates the safety and efficacy of DUR (10 mg/kg every 2 weeks) in 5 GBM cohorts with and without BEV. This report presents the safety and efficacy for Cohort B (BEV-naïve recurrent GBM; DUR monotherapy). The primary efficacy endpoint for Cohort B is progression-free survival at 6 months (PFS-6), based on modified RANO criteria by investigator assessment; secondary endpoints include safety/tolerability. A PFS-6 of 10% is the comparative historical benchmark (pre-BEV), based on published meta-analyses. The null hypothesis (PFS-6 ≤ 10%) was tested in the Intent-to-Treat (ITT) population against the alternative hypothesis (PFS-6 > 10%) at α = 0.05, using 90% confidence interval (CI). The null hypothesis was rejected if the lower bound of the CI was > 10%. ITT includes patients receiving any dose of DUR and having at least baseline and 1 post-baseline tumor assessment. Results: The first patient was dosed on 05Mar2015, and the data cutoff was 05Feb2016. Cohort B completed enrollment of 31 patients (male: 83.9%; mean age: 54.0 [24-77] years; baseline ECOG Performance Status (PS) 0: 51.6%, PS 1: 48.4%; baseline measurable lesions: 77.4%). Incidences of treatment-related adverse events (TRAEs) by maximum CTCAE grade (Gr) were Gr1: 35.5%; Gr2: 41.9%; Gr3: 9.7%; and Gr4/5: 0%. Most common TRAEs (≥3 (9.7%) patients) were fatigue, headache, hemiparesis, increased AST, and decreased platelets, WBCs and lymphocytes. Thirty patients were evaluable for efficacy (PFS), and 6 were progression free at 6 months. Kaplan-Meier estimate for PFS-6 was 20%. Conclusions: DUR appears to be well tolerated and shows activity in BEV-naïve recurrent GBM, although the primary PFS-6 endpoint was not met. Further studies are warranted. Citation Format: David A. Reardon, Thomas Kaley, Jorg Dietrich, Michael Lim, Gavin P. Dunn, Hui K. Gan, Timothy Cloughesy, Jennifer L. Clarke, Andrew Park, Mary Macri, Aileen Ryan, Toni Ricciardi, Vijay Reddy, Ralph Venhaus. Phase II study to evaluate the clinical efficacy and safety of MEDI4736 (durvalumab) in patients with glioblastoma (GBM): Results for cohort B (durvalumab monotherapy), bevacizumab-naïve patients with recurrent GBM [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA20.

949O - Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort

949O - Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort

Safety and efficacy of durvalumab (MEDI4736), a PD-L1 antibody, in urothelial bladder cancer.

4502Background: A Phase 1/2 dose escalation and dose expansion study is evaluating the safety and efficacy of durvalumab, a modified human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, in so...