Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Keilholz, Ulrich; Mehnert, Janice M.; Bauer, Sebastian; Bourgeois, H.; Patel, Manish R.; Gravenor, Donald S.; Nemunaitis, John; Taylor, Matthew H.; Wyrwicz, Lucjan; Lee, Moon Hyoung; Kasturi, Vijay; Chin, Kevin M.; Heydebreck, Anja von; Gulley, James L.

doi:10.1186/s40425-018-0459-y

Cited by 76 publications

(42 citation statements)

References 29 publications

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“…Heterogeneity: I 2 = 92%, τ 2 = 0.5527, p < 0.01 Rittmeyer et al [79] Fehrenbacher et al [87] Powles et al [81] Barlesi et al [97] Bang et al [121] Peters et al [80] Petrylak et al [82] Colevas et al [86] Horn et al [85] Lukas et al [84] Spigel et al [83] McDermott et al [77] Gulley et al [90] Dirix et al [93] Chung et al [102] Disis et al [101] Kelly et al [95] Keilholz et al [100] Hassan et al [99] Le et al [98] Antonia et al [104] Yang et al [107] Massard et al [103] Segal et al [111] Zandberg et al [110] Siu et al [109] Herbst et al [76] Garassino et al […”

Section: Fixed Effect Model Random Effects Modelmentioning

confidence: 99%

“…This analysis compared 11 different ICI-related (grade 1-5 and 3-5) AEs, including a total of 147 studies and 23 761 patients. The interventions were: 46 pembrolizumab articles (n = 6598), 27 nivolumab articles (n = 3576), 13 atezolizumab articles (n = 2787), [76][77][78][79][80][81][82][83][84][85][86][87][88] 12 avelumab articles (n = 3213), [89][90][91][92][93][94][95][96][97][98][99][100][101][102] 10 durvalumab articles (n = 1780), [103][104][105][106][107][108][109][110][111] 22 ipilimumab articles (n = 4067) 5, ; eight tremelimumab articles (n = 1158), [133][134][135][136][137][138][139][140] three JS001 articles (n = 223), [141][142]…”

Section: Basic Characteristics Of the Literaturementioning

confidence: 99%

“…Heterogeneity: I 2 = 89%, τ 2 = 0.6776, p < 0.01 Barlesi et al [97] Bang et al [121] Gulley et al [90] Dirix et al [93] Chung et al [102] Disis et al [101] Kelly et al [95] Keilholz et al [100] Hassan et al [99] Le et al […”

Section: Fixed Effect Model Random Effects Modelmentioning

confidence: 99%

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Meta‐analysis of immune‐related adverse events of immune checkpoint inhibitor therapy in cancer patients

et al. 2020

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Background Immune checkpoint inhibitors (ICIs) have significant clinical efficacy in the treatment of non‐small cell lung cancer (NSCLC); however, the incidence of immune‐related adverse events (irAEs) of up to 50% has prevented their widespread use. With the increase in the use of ICIs alone or as combination therapy, clinicians are required to have a better understanding of irAEs and be able to manage them systematically. In this study, we aimed to assess the incidence of irAEs associated with ICIs. Methods We searched PubMed, Embase, and the Web of Science databases, and also included relevant literature references to widen our search. The relevant data with inclusion criteria were performed using RevMan 3.6.0 for meta‐analysis. We undertook a systematic literature search which included published data up to December 2019. Results Overall, 147 articles and 23 761 cancer patients with 11 different ICI treatment‐related (grade 1–5 and 3–5) irAEs were included in the study. There were 46 articles on pembrolizumab (6598 patients), 27 on nivolumab (3576 patients), 13 on atezolizumab (2787 patients), 12 on avelumab (3213 patients), 10 on durvalumab (1780 patients), 22 on ipilimumab (4067 patients), eight on tremelimumab (1158 patients), three on JS001 (223 patients), four on camrelizumab (SHR‐1210) (178 patients), one on sintilimab (96 patients), and one on cemiplimab (85 patients). Grade 1–5 irAEs were: cytotoxic T lymphocyte antigen 4 (CTLA‐4) (82.87%), programmed cell death 1 (PD‐1) (71.89%), and programmed cell death ligand‐1 (PD‐L1) (58.95%). Subgroup analysis was: Avelumab (44.53%), durvalumab (66.63%), pembrolizumab (67.25%), atezolizumab (68.77%), nivolumab (76.25%), Ipilimumab (82.18%), and tremelimumab (86.78%). Grade 3–5 irAEs were: CTLA‐4 (27.22%), PD‐1(17.29%), and PD‐L1(17.29%). Subgroup analysis was: Avelumab (5.86%), durvalumab (13.43%), atezolizumab (14.45%), nivolumab (15.72%), pembrolizumab (16.58%), tremelimumab (22.04%), and ipilimumab (28.27%). Conclusions This meta‐analysis confirmed that anti‐PD‐1 and anti‐PD‐L1 inhibitors had a lower incidence of irAEs compared with anti‐CTLA‐4 inhibitors.

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Section: Fixed Effect Model Random Effects Modelmentioning

confidence: 99%

Section: Basic Characteristics Of the Literaturementioning

confidence: 99%

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Meta‐analysis of immune‐related adverse events of immune checkpoint inhibitor therapy in cancer patients

et al. 2020

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“…10 11 In previous clinical trials, avelumab has demonstrated clinical activity and a tolerable safety profile in patients with various other tumor types, including platinum-treated NSCLC. [12][13][14][15][16] Here, we report efficacy and safety data from a phase I expansion cohort of the JAVELIN Solid Tumor trial in which patients with advanced NSCLC received first-line avelumab. Preliminary findings from this cohort led to the initiation of the phase III JAVELIN Lung 100 study (NCT02576574) of first-line avelumab versus platinum-based doublet chemotherapy in patients with PD-L1-positive NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study

Verschraegen

Jérusalem

McClay

et al. 2020

J Immunother Cancer

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IntroductionAvelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).MethodsIn a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.ResultsOverall, 156 patients were enrolled and treated. Median duration of follow-up was 18.6 months (range, 15 to 23 months). The objective response rate was 19.9% (95% CI, 13.9 to 27.0), including complete response in 3 (1.9%) and partial response in 28 (17.9%). Median DOR was 12.0 months (95% CI, 6.9 to not estimable). Median PFS was 4.0 months (95% CI, 2.7 to 5.4) and the 6-month PFS rate was 38.5% (95% CI, 30.7 to 46.3). Median OS was 14.1 months (95% CI, 11.3 to 16.9) and the 12-month OS rate was 56.6% (95% CI, 48.2 to 64.1). Treatment-related adverse events (TRAEs) occurred in 107 patients (68.6%), including grade ≥3 TRAEs in 19 (12.2%). Immune-related adverse events and infusion-related reactions occurred in 31 (19.9%) and 40 patients (25.6%), respectively. No treatment-related deaths occurred.ConclusionAvelumab showed antitumor activity with a tolerable safety profile as a first-line treatment in patients with advanced NSCLC. These data support further investigation of avelumab in the phase III JAVELIN Lung 100 study.Trial registration detailsClinicalTrials.gov NCT01772004; registered January 21, 2013.

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“…In 9 May 2017, the FDA granted accelerated approval to avelumab for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy based on the JAVELIN Solid Tumor trial [75] (Category 2A, alternative to preferred agent pembrolizumab, which is category 1). On 14 May 2019, the FDA approved avelumab in combination with axitinib (Inlyta) for the first-line treatment of patients with advanced RCC and it is the first FDA approval for an anti-PD-L1 therapy as part of a combination regimen for patients with advanced RCC.…”

mentioning

confidence: 99%

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence

Vaddepally

Kharel

Pandey

et al. 2020

Cancers

969

765

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Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.

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Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Cited by 76 publications

References 29 publications

Meta‐analysis of immune‐related adverse events of immune checkpoint inhibitor therapy in cancer patients

Meta‐analysis of immune‐related adverse events of immune checkpoint inhibitor therapy in cancer patients

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence

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