Two-year efficacy and safety update from JAVELIN Merkel 200 part A: A registrational study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy.

Nghiem, Paul; Bhatia, Shailender; Brohl, Andrew S.; Hamid, Omid; Mehnert, Janice M.; Terheyden, Patrick; Shih, Kent C.; Brownell, Isaac; Lebbe, Célèste; Lewis, Karl D.; Linette, Gerald P.; Milella, Michèle; Hennessy, Meliessa; Bajars, Marcis; Hicking, Christine; D’Angelo, Sandra P.

doi:10.1200/jco.2018.36.15_suppl.9507

Cited by 39 publications

(40 citation statements)

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“…This phenomenon has been observed with other similar monoclonal antibodies, including nivolumab, pembrolizumab, and atezolizumab, for which mean maximum decreases of 24.5% (nivolumab in metastatic NSCLC, advanced renal cell carcinoma, and SCCHN), 20% (pembrolizumab in melanoma and NSCLC), and 17.1% (atezolizumab in NSCLC) have been reported . Consistent with other similar monoclonal antibodies, no dose adjustment is warranted for avelumab because clinical studies have shown that the benefit/risk balance is maintained with long‐term treatment …”

Section: Discussionmentioning

confidence: 99%

“…9 Consistent with other similar monoclonal antibodies, no dose adjustment is warranted for avelumab because clinical studies have shown that the benefit/risk balance is maintained with long-term treatment. 14 In patients with Merkel cell carcinoma, the timedependent effect on CL may reflect that these patients were followed longer than patients with other tumor types. The mMCC group had a median treatment duration of 105 days vs. 74 days in the total population.…”

Section: Discussionmentioning

confidence: 99%

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Time‐Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma

Wilkins¹,

Brockhaus

Dai

et al. 2019

CPT Pharmacom & Syst Pharma

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Avelumab, a human anti–programmed death ligand 1 immunoglobulin G1 antibody, has shown efficacy and manageable safety in multiple tumors. A two‐compartment population pharmacokinetic model for avelumab incorporating intrinsic and extrinsic covariates and time‐varying clearance ( CL ) was identified based on data from 1,827 patients across three clinical studies. Of 14 tumor types, a decrease in CL over time was more notable in metastatic Merkel cell carcinoma and squamous cell carcinoma of the head and neck, which had maximum decreases of 32.1% and 24.7%, respectively. The magnitude of reduction in CL was higher in responders than in nonresponders. Significant covariate effects of baseline weight, baseline albumin, and sex were identified on both CL and central distribution volume. Significant covariate effects of black/African American race, C‐reactive protein, and immunogenicity were found on CL . None of the covariate or time‐dependent effects were clinically important or warranted dose adjustment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Time‐Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma

Wilkins¹,

Brockhaus

Dai

et al. 2019

CPT Pharmacom & Syst Pharma

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“…Avelumab (antieprogrammed cell death ligand 1 [PD-L1]), pembrolizumab (antieprogrammed cell death protein 1 [PD-1]), and nivolumab (PD-1) have shown antitumor activity in patients with metastatic disease and are indicated in this population. 11,12,[15][16][17][18][19][20][21] Their efficacy as neoadjuvant treatment, however, remains to be determined.…”

mentioning

confidence: 99%

Heart Block Caused by Cardiac Metastasis From Merkel Cell Carcinoma: A Case Report

Kazemi

Jain

Bois

et al. 2019

Mayo Clinic Proceedings: Innovations, Quality & Outcomes

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Merkel cell carcinoma (MCC) is a rare, rapidly proliferating skin cancer that commonly metastasizes to regional lymph nodes. We present the case of a 73-year-old woman with a history of MCC and non-Hodgkin B-cell lymphoma who presented with second-degree heart block (Mobitz type II) caused by an interatrial mass. Temporary pacing was required before biopsy, which revealed metastatic MCC. Treatment included permanent pacing, antieprogrammed cell death ligand 1 immunotherapy, and radiation to the heart resulting in notable decrease in tumor size and normalized cardiac rhythm.

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“…Two‐year PFS and OS rates were 26% (29% at 1 year) and 36% (50% at 1 year), respectively. Median PFS was 2.7 months and median OS was 12.6 months, which is highly favorable for patients in this setting considering historical chemotherapy data (Table ) . Durable antitumor efficacy was observed across all patient subgroups (MCPyV‐positive, MCPyV‐negative, PD‐L1‐positive, and PD‐L1‐negative patients), although there was a trend toward a greater response rate in patients with PD‐L1‐positive as compared with PD‐L1‐negative tumors (36% vs 19%, respectively) .…”

Section: Treatment Of Metastatic MCC (M1)mentioning

confidence: 85%

“…Avelumab is a fully human IgG1 anti-PD-L1 antibody that preserves antibody-mediated cytotoxicity [49]. The efficacy of avelumab was investigated in the JAVELIN Merkel 200 phase II trial, which has two main parts (A and B) [3,44,50,51]. Durable antitumor efficacy was observed across all patient subgroups (MCPyV-positive, MCPyV-negative, PD-L1-positive, and PD-L1-negative patients), although there was a trend toward a greater response rate in patients with PD-L1positive as compared with PD-L1-negative tumors (36% vs 19%, respectively) [38,50].…”

Section: Immunotherapymentioning

confidence: 99%

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma

et al. 2019

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Merkel cell carcinoma (MCC) is a rare, aggressive, primary cutaneous neuroendocrine tumor that typically presents as an indurated nodule on sun‐exposed areas of the head and neck in the white population. Major risk factors include immunosuppression, UV light exposure, and advanced age. Up to 80% of MCC are associated with Merkel cell polyomavirus. About 50% of patients present with localized disease, and surgical resection with or without adjuvant radiotherapy is generally indicated in this context. However, recurrence rates are high and overall prognosis rather poor, with mortality rates of 33%–46%. MCC is a chemosensitive disease, but responses in the advanced setting are seldom durable and not clearly associated with improved survival. Several recent trials with checkpoint inhibitors (pembrolizumab, avelumab, nivolumab) have shown very promising results with a favorable safety profile, in both chemonaïve and pretreated patients. In 2017, avelumab was approved by several regulatory agencies for the treatment of metastatic MCC, the first drug to be approved for this orphan disease. More recently, pembrolizumab has also been approved by the U.S. Food and Drug Administration in this setting. Immunotherapy has therefore become the new standard of care in advanced MCC. This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group. Implications for Practice Merkel cell carcinoma (MCC) is an uncommon aggressive skin cancer associated with advanced age, UV light exposure, and immunosuppression. Up to 80% are associated with Merkel cell polyomavirus. MCC is a chemosensitive disease, but tumor responses in the advanced setting are short‐lived with no long‐term survivors. Recent clinical trials with immune checkpoint inhibitors (i.e., pembrolizumab, avelumab, nivolumab) have shown promising results, with avelumab becoming the first drug to receive regulatory approval for this orphan indication. Further follow‐up is needed, however, to define more adequately the long‐term benefits of these drugs, and continued research is warranted to optimize immunotherapeutic strategies in this setting.

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Two-year efficacy and safety update from JAVELIN Merkel 200 part A: A registrational study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy.

Cited by 39 publications

References 0 publications

Time‐Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma

Time‐Varying Clearance and Impact of Disease State on the Pharmacokinetics of Avelumab in Merkel Cell Carcinoma and Urothelial Carcinoma

Heart Block Caused by Cardiac Metastasis From Merkel Cell Carcinoma: A Case Report

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma

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