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

Abstract

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.

Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel

“…81 82 Results from Italian patients enrolled in the avelumab EAP were consistent with the findings of the JAVELIN Merkel 200 trial and confirmed the efficacy and safety of avelumab treatment in this population. 83 Infusion-related reaction, fatigue, and rashes were among the most frequently occurring and importantly no new safety signals were identified in the EAP population. 84 As for the mMCC setting, ICI drastically changed prognosis of a proportion of patients with advanced MCC, as it happened in other oncological fields.…”

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival

“…5 Similarly, Europe, China, and Australia have all seen rising incidences over the past several years. [6][7][8][9][10] While incidence data in Latin America and parts of Asia are scarce, multiple studies have shown that fair-skinned individuals have twice the risk when compared to the general population. 7,[11][12][13][14] Current studies have examined a wide range of populations, including the US, Latin America, the Netherlands, Italy, Israel, and the Middle East.…”

“…19,20 Patient demographics seen in real-world studies are described in Table 1. 3,9,[11][12][13][21][22][23] Although MCC is reported to occur predominantly on the head and neck, an analysis of 54 advanced MCC patients conducted in the Netherlands, indicated that tumors occurred on the trunk, head and neck, and extremities 15%, 24%, and 46% of the time, respectively. 21,24 In another study, primary tumor locations were lower limbs, lungs, and viscera, which metastasized to the lymph nodes 38%, 52%, and 68% of the time, respectively.…”

Identifying Candidates for Immunotherapy among Patients with Non-Melanoma Skin Cancer: A Review of the Potential Predictors of Response

“…Meanwhile, the global avelumab program expanded access, which was designed to provide the compassionate use of avelumab prior to approval and led to similar response rates. The main treatment-related adverse events reported were infusion-related reactions and pyrexia [ 101 , 102 ].…”