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

D’Angelo, Sandra P.; 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; Georges, Sara; Shah, Parantu K.; Ellers‐Lenz, Barbara; Bajars, Marcis; Güzel, Gülseren; Nghiem, Paul

doi:10.1136/jitc-2020-000674

Cited by 151 publications

(188 citation statements)

References 28 publications

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“…The ORR to nivolumab was also regardless of the viral state of the tumor [ 248 ]. The ORR in VP-MCC patients ( n = 23) and VN-MCC patients was 26% and 46%, respectively of the VN-MCC patients ( n = 13), while in another study including 46 VP-MCC and 31 VN-MCC patients, the ORR was 28% and 36%, respectively [ 249 ]. Treatment of five MCC patients with ipilimumab indicated a positive activity of ipilimumab, but the viral state of the patients was not reported [ 250 ].…”

Section: Vp-mcc Specific Therapymentioning

confidence: 99%

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Pietropaolo¹,

Prezioso

Moens

2020

Cancers

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Viruses are the cause of approximately 15% of all human cancers. Both RNA and DNA human tumor viruses have been identified, with Merkel cell polyomavirus being the most recent one to be linked to cancer. This virus is associated with about 80% of Merkel cell carcinomas, a rare, but aggressive cutaneous malignancy. Despite its name, the cells of origin of this tumor may not be Merkel cells. This review provides an update on the structure and life cycle, cell tropism and epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are discussed.

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Section: Vp-mcc Specific Therapymentioning

confidence: 99%

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Pietropaolo¹,

Prezioso

Moens

2020

Cancers

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“…This is substantiated by the updated results of the JAVELIN trial after a median follow-up of 41 months, where a trend towards a higher ORR in patients with fewer prior lines of therapy was seen. 24 This could explain the higher RR in our cohort as we had no patients with more than one prior line of therapy.…”

Section: Discussionmentioning

confidence: 93%

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort

Levy

Aarts

Eskens

et al. 2020

J Immunother Cancer

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BackgroundMerkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported.MethodsPatients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.ResultsFifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5–35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3–22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6–15.5) months, and the median OS was 25.8 (95% CI 9.1–42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4–5 toxicity was seen.ConclusionsIn this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC.

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“…In particular, avelumab became the first approved treatment for patients with mMCC in 2017 based on results from JAVELIN Merkel 200, a phase 2, single-arm trial (NCT02155647) [10]. After 3 years of follow-up from part A of the trial, which enrolled 88 patients with progressive disease (PD) who had received prior chemotherapy, the objective response rate (ORR) was 33.0% (95% CI 23.3-43.8%), including complete response (CR) in 11.4% [11]. After ≥ 15 months of follow-up in part B, in which 116 patients with mMCC and no prior systemic treatment for metastatic disease were treated with avelumab, 30.2% of patients had a response lasting ≥ 6 months (durable response rate), and the ORR was 39.7% (95% CI 30.7-49.2%), including CR in 16.4% [12].…”

Section: Journal Of Translational Medicinementioning

confidence: 99%

“…After ≥ 15 months of follow-up in part B, in which 116 patients with mMCC and no prior systemic treatment for metastatic disease were treated with avelumab, 30.2% of patients had a response lasting ≥ 6 months (durable response rate), and the ORR was 39.7% (95% CI 30.7-49.2%), including CR in 16.4% [12]. In both parts A and B of the trial, responses were seen irrespective of PD-L1 or MCPyV status; however, numerically higher ORRs were reported in patients with PD-L1+ vs. PD-L1− tumors (part A, PD-L1+ [ [11,12]. Avelumab has subsequently been approved in various countries worldwide for the treatment of mMCC, including in Europe [13].…”

Section: Journal Of Translational Medicinementioning

confidence: 99%

Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program

et al. 2021

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Background The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP. Methods Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician’s discretion. Results Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5–41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]). Conclusions Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

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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

Cited by 151 publications

References 28 publications

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Merkel Cell Polyomavirus and Merkel Cell Carcinoma

Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort

Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program

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