scholarly journals Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000674 ◽  
Author(s):  
Sandra P D'Angelo ◽  
Shailender Bhatia ◽  
Andrew S Brohl ◽  
Omid Hamid ◽  
Janice M Mehnert ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Objective Response ◽  
Safety Data ◽  
Phase 2 ◽  
Merkel Cell ◽  
Term Survival ◽  
Duration Of Response

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti–programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.MethodsIn a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses.ResultsAs of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4–49.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95% CI 18.0 months to not estimable). As of 2 May 2019 (≥44 months of follow-up), the median OS was 12.6 months (95% CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS >36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (≥2 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (≥36 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred.ConclusionsAvelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease.Trial registration numberNCT02155647

18-month efficacy and safety update from JAVELIN Merkel 200 part A: A phase II study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Jeffery Scott Russell ◽  
Shailender Bhatia ◽  
Omid Hamid ◽  
Janice M. Mehnert ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Merkel Cell ◽  
Efficacy And Safety ◽  
Duration Of Response ◽  
Grade 3

192 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Avelumab, a human anti–PD-L1 monoclonal antibody, is FDA and EMA approved for the treatment of metastatic MCC (mMCC). Here, we report efficacy and safety data for avelumab in patients (pts) with mMCC at ≥18-mo of follow-up. Methods: Pts with mMCC and progression on prior chemotherapy received avelumab 10 mg/kg IV Q2W. Objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were evaluated by independent review committee (RECIST v1.1) with tumor assessment every 6 wks; overall survival (OS) and adverse events (AEs; NCI CTCAE v4.0) were also evaluated. Results: As of Mar 24, 2017, 88 pts were treated and followed for a median of 23.0 mo (range 18.7–32.0). Median treatment duration was 17 wks (range 2–132; mean 35 wks ±37). Treatment was ongoing in 15 pts (17%); 7 pts (8%) voluntarily discontinued with continuing responses (5 complete responses [CR] and 2 partial responses). Other reasons for discontinuation were disease progression (n = 42; 48%), death (n = 10; 11%), AE (n = 8; 9%), or consent withdrawal/other (n = 6; 7%). Confirmed ORR of 33% (95% CI 23.3–43.8; CR in 11.4%) remained unchanged from previous analysis and median DOR has not been reached (range 2.8–24.9 mo; 95% CI 18.0–not estimable). Responses were ongoing in 20/29 pts (69%), including 5 pts with > 2 y of follow-up. PFS curve showed a plateau with identical 12- and 18-mo rates of 29% (95% CI 19–39). Median OS was 12.6 mo (95% CI 7.5-19.0) and the 12- and 18-mo OS rates were 51% (95% CI 40–61) and 40% (95% CI 29–50), respectively. 66 pts (75%) had a treatment-related (TR)AE, most commonly ( > 10%) fatigue (25%), infusion-related reaction (15%; all grade 1/2), nausea (11%), and diarrhea (11%); 8 (9%) had a grade ≥3 TRAE. 17 pts (19%) had an immune-related AE, which was grade ≥3 in 4 pts (4.5%). No treatment-related deaths occurred. Conclusions: Updated results demonstrate continued durable antitumor activity of avelumab in pts with mMCC, beyond that expected with cytotoxic chemotherapy. The median OS exceeding 1 y and manageable safety profile of avelumab signify a clinically meaningful benefit in pts with mMCC. Clinical trial information: NCT02155647.

scholarly journals 934 Biological mechanisms in the different etiologies of Merkel cell carcinoma patients: polyomavirus or UV exposure

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A980-A980
Author(s):  
Domenico Mallardo ◽  
Giosuè Scognamiglio ◽  
Khrystyna North ◽  
Mariaelena Capone ◽  
Michael Bailey ◽  
...  
Keyword(s):  
Informed Consent ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Uv Exposure ◽  
List Type ◽  
Phase 2 ◽  
Merkel Cell ◽  
Term Survival

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer with neuroendocrine features, and it is associated with elevated mortality. The pathogenesis is associated with presence of clonally integrated Merkel cell polyomavirus (MCPyV) or ultraviolet light (UV) exposure.1 The MCPyV causes up to 80% of MCC tumors in North America and Europe.2–4 Recently immunotherapy is having good results,5 the phase 2 trial JAVELIN Merkel 200 indicated that treatment with Avelumab (PDL1 inhibitor) in patients with metastatic MCC pre-treated have a meaningful long-term survival outcomes respect chemotherapy. Moreover, ORRs were highest in patients with high TMB that were also MCPyV−, PD-L1+ or had a greater CD8+ T cell density at the invasive margin.6 In this study, we investigated the biological signatures in patients with MCPyV or not.MethodsFrom April 2011 to June 2018, we collected retrospectively 50 FFPE (Formalin-Fixed Paraffin-Embed) from 37 patients with metastatic MCC and 13 tissues from a secondary metastatic site. All patients have appropriately signed informed consent. We performed an immunohistochemistry assays (IHC) for MCPyV and PDL1. In addition, through the NanoString GeoMx DSP (Digital Spatial Profiling), we analysed 11 patients (6 MCPyV+; 5 MCPyV-) with cutaneous metastasis using a 44-plex antibody cocktail. For each slide we selected three different areas: Intratumoral, extratumoral and tumour border, in each area we selected CD4+ and CD8+ cells in 4 different ROIs (Region of Interest). Statistical analysis was performed via Bonferroni correction, P< 0.05 was considered statistically significant for median stratification.ResultsThe DSP analysis showed that the tumour border cells have an overexpression of IDO respect intratumoral area (adj. p<0.01). Instead, extratumoral area of MCPyV- patients have a higher expression of B7-H3 respect MCPyV+ as well as FOXP3 is higher in the tumour border of MCPyV+ patients and EpCAM in the intratumoral area (p<0.05). PDL1 is overexpressed in MCPyV+ CD4+ cells respect CD8+ (p<0.05). The IHC assay shown that viral status does not change in multiple metastases and PDL1 is elevated in the tumour border (p<0.05).ConclusionsIn this retrospective study, our preliminary data shown that tumour edge have an important role in the modulations of immune infiltrate and patients with Merkel cell polyomavirus could have a different pathway of immunosuppression compared to patients with non-virus related etiology. Further investigations are needed to get additional information.AcknowledgementsThe study was supported by the Institutional Project ”Ricerca Corrente” of Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli, Italy.ReferencesKaae J, Hansen AV, Biggar RJ, et al. Merkel cell carcinoma: incidence, mortality, and risk of other cancers. J Natl Cancer Inst 2010 June 2;102(11):793–801.Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008 February 22;319(5866):1096–100.Garneski KM, Warcola AH, Feng Q, et al. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009 January;129(1):246–8.Goh G, Walradt T, Markarov V, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget 2016 January 19;7(3):3403–15.Bichakjian CK, Olencki T, Aasi SZ, et al. Merkel cell carcinoma, version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2018 June;16(6):742–774.D’Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer 2020 May;8(1):e000674.Ethics ApprovalThe study was approved by internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli Italy, approval number of registry 33/17 OSS.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Avelumab in patients with previously treated Merkel cell carcinoma (JAVELIN Merkel 200): Updated overall survival data after more than five years of follow up.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Andrew S. Brohl ◽  
Omid Hamid ◽  
Janice M. Mehnert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Merkel Cell Carcinoma ◽  
Survival Data ◽  
Safety Data ◽  
Additional Patient ◽  
Merkel Cell

9517 Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is considered chemosensitive, patients typically have limited survival benefit with chemotherapy. Before the approval of immune checkpoint inhibitors, patients with metastatic MCC (mMCC) had a poor prognosis, with a historical 5-year overall survival (OS) rate of approximately 14%. Avelumab (anti–PD-L1) became the first approved treatment for patients with mMCC, based on efficacy and safety data observed in the phase 2 JAVELIN Merkel 200 trial (NCT02155647), in which patients with mMCC received avelumab monotherapy. We report the long-term OS data from the cohort of patients with mMCC whose disease had progressed after ≥1 prior line of chemotherapy. Methods: Eligible patients had histologically confirmed, measurable (per RECIST 1.1) stage IV MCC. Patients received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. Long-term OS was analyzed; updated data for other efficacy endpoints, including response and progression-free survival, were not obtained. Results: A total of 88 patients were enrolled and received avelumab treatment. As of September 25, 2020 (data cutoff), median follow-up was 65.1 months (range, 60.8-74.1 months). Median OS was 12.6 months (95% CI, 7.5-17.1 months); the 48- and 60-month OS rates were 30% (95% CI, 20%-40%) and 26% (95% CI, 17%-36%), respectively. At data cutoff, treatment was ongoing in 1 patient (1.1%) and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Reasons for treatment discontinuation were disease progression (n = 45 [51.1%]), adverse event (AE; n = 11 [12.5%]), death (n = 10 [11.4%]), withdrawal of consent (n = 9 [10.2%]), loss to follow-up (n = 1 [1.1%]), protocol noncompliance (n = 1 [1.1%]), and other reason (n = 10 [11.4%]). At data cutoff, 19 patients (21.6%) had discontinued treatment but remained in follow-up, and 63 patients (71.6%) had died; causes of death were disease progression (n = 49 [55.7%]), unknown reason (n = 9 [10.2%]), AE not related to study treatment (n = 3 [3.4%]), and other reason (n = 2 [2.3%]). In total, 26 patients (29.5%) received subsequent anticancer therapy; the most common subsequent therapies after trial discontinuation were avelumab (n = 4 [4.5%]), carboplatin and etoposide (n = 4 [4.5%]), and pembrolizumab (n = 4 [4.5%]). Conclusions: Avelumab monotherapy led to meaningful long-term OS in a subset of patients with mMCC whose disease had progressed after chemotherapy. These results further support the role of avelumab as a standard-of-care treatment for patients with mMCC. Clinical trial information: NCT02155647.

Long-Term Follow-Up of Patients Treated With Radiation Therapy for Merkel Cell Carcinoma of the Head and Neck

2014 ◽  
Vol 90 (1) ◽  
pp. S555
Author(s):  
J.M. Shulman ◽  
E. Fernandez ◽  
D. Dosoretz ◽  
C.A. Mantz ◽  
A.D. Fox ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Long Term Follow Up

Projecting long term survival for avelumab in refractory Merkel cell carcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21623-e21623 ◽  
Author(s):  
Hemant Phatak ◽  
Irina Proskorovsky ◽  
Tereza Lanitis ◽  
Apoorva Ambavane ◽  
Matthias Hunger ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status

2019 ◽  
Vol 25 (2) ◽  
Author(s):  
Constantin A Dasanu ◽  
Michael Del Rosario ◽  
Ion Codreanu ◽  
Yani Lu ◽  
Stephanie Farrell ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Single Institution ◽  
Immunological Status ◽  
Long Term Follow Up

scholarly journals 329 Impact of ultraviolet exposure on merkel cell carcinoma long-term survival

2018 ◽  
Vol 138 (5) ◽  
pp. S56
Author(s):  
A. Guo ◽  
I.N. Sarkar ◽  
E. Chen ◽  
J. Walker ◽  
P. Stey ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Term Survival ◽  
Long Term Survival ◽  
Ultraviolet Exposure

scholarly journals Primary Merkel cell carcinoma of the eyelid - clinical, histopathological, immunohistochemical and electron microscopical features: A case report

2015 ◽  
Vol 143 (5-6) ◽  
pp. 309-313 ◽  
Author(s):  
Anica Bobic-Radovanovic ◽  
Zoran Latkovic ◽  
Milica Labudovic-Borovic ◽  
Dejan Rasic
Keyword(s):  
Case Report ◽  
Early Diagnosis ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Optimal Therapy ◽  
Electron Microscopical

Introduction. Merkel cell carcinoma (MCC) is a rare eyelid neoplasm which can cause significant diagnostic and especially therapeutic challenges. Case Outline. This is the first documented report of the case of primary MCC of the eyelid in Serbia. Conclusion. The optimal therapy must be individualized in any given patient and, early diagnosis and meticulous follow-up are mandatory to achieve a long-term cure.

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