Real-world Merkel cell carcinoma outcomes from a tertiary care center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14098-e14098
Author(s):  
Theresa N Canavan ◽  
Nicole Adell Doudican ◽  
Mary Stevenson ◽  
Anna C. Pavlick ◽  
John Carucci
Keyword(s):  
Cell Carcinoma ◽  
Disease Progression ◽  
Merkel Cell Carcinoma ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Merkel Cell ◽  
New York University ◽  
Relapse Free Survival ◽  
Free Survival

e14098 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin that is highly immunogenic. Checkpoint inhibitors (CPI) have recently revolutionized the treatment of advanced MCC. In this study we sought to better understand how CPI are used in an outpatient setting and to better define MCC outcomes associated with their use. Methods: We conducted a retrospective chart review of MCC patients seen in the New York University Hematology and Oncology Department from 2012-2018. Patient characteristics and treatment regimens were compared between those with and without disease progression at any point during follow-up. Results: Fifteen patients were identified, 46.7% of whom presented with nodal or distant disease (Table). Nine patients experienced relapse during follow-up. There were no MCC-specific deaths, and 92.3% of patients were without evidence of MCC at the end of follow-up. Ten patients were treated with one or more CPI (pembrolizumab, nivolumab, ipilimumab) either in the setting of first line systemic therapy (71.4%) or after experiencing disease progression (28.6%). There was a trend toward improved relapse free survival with CPI use (P = 0.054). Conclusions: Although recurrences were common, overall outcomes at the end of follow-up were very good. CPI were well tolerated and were associated with a trend toward improved relapse free survival. Patients with advanced stage MCC would benefit from consideration of CPI as part of their treatment options. [Table: see text]

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.

Is CTLA4 targeting the Achilles’ heel of Merkel cell carcinoma?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21567-e21567
Author(s):  
Richard Cheng Han Wu ◽  
Kari Lynn Kendra ◽  
Dukagjin Blakaj ◽  
Hiral A. Shah ◽  
Joanne M. Jeter ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Neuroendocrine Differentiation ◽  
Stage Iv ◽  
Lymph Node Involvement ◽  
Primary Objective ◽  
Merkel Cell ◽  
Number Of Patients

e21567 Background: Merkel Cell Carcinoma (MCC) is a cutaneous malignancy with neuroendocrine differentiation, linked to infection with polyomavirus (MCPyV) in 80% of cases. PD1 inhibitors have recently been approved for this indication with ORR, 33-56%; CR, 11-24%; PFS, about 17 months; OS, about 12 months. Nivolumab was tested in the neoadjuvant setting with similar responses with pathological CR, 47%. Methods: Adjuvant pilot study (NCT03798639) with two immunotherapy regimens administered for one year to patients with completely resected MCC at high risk of recurrence (primary lesion of 2 cm or greater, positive or close margins ( < 2 cm), perineural or lymphovascular invasion, mitotic index ≥ 20 mitotic figures per mm2, lymph node involvement (stage pIIIA or pIIIB) with or without extracapsular extension, or completely resected stage IV disease). Arm 1, nivolumab 480 mg q 4 wks and radiation therapy (RT) 50-60 Gy in 25-30 fractions, per standard of care. Arm 2, nivolumab 240 mg q 2 wks and ipilimumab 1 mg/kg q 6 wks. Primary objective was feasibility and completion of treatment in this population. Safety profile (CTCAE v5.0) and recurrence-free survival (RFS) after 18 months were secondary endpoints. Patients were randomly allocated 1:1. Results: Ten patients were screened from January 2019 until April 2020, when COVID put the study on hold and the sponsor discontinued the free drug supply. Seven were enrolled. Four were allocated to Arm 1 and three to Arm 2. Patient characteristics in Table. All patients have completed treatment and are in follow-up. Arm 1: all four patients completed radiation therapy and immunotherapy with no dose modifications or delays. Arm 2: one patient had nivolumab delayed 2 weeks for cellulitis, and another missed the last four last doses of nivolumab for cholecystitis and pancreatitis requiring surgery, unrelated to the immunotherapy. Adverse events (AE) were as expected. Arm1 caused more grade 2 and 3 AEs then Arm2 (no grade 3). One patient each discontinued treatment, in Arm 1 for progression and Arm 2 for immunotoxicity (temporal arteritis grade 2). One recurrence was observed in Arm 1 and none in Arm 2. Conclusions: The number of patients expected to recur at 1 year is 20%. Our observed data is insufficient to establish efficacy. However with no patient recurring in the ipilimumab arm after 18 months of follow-up and lower observed side effects, we would favor this regimen for the next trial. Clinical trial information: NCT03798639. [Table: see text]

Multidisciplinary team approach for Merkel cell carcinoma: the European Institute of Oncology experience with focus on radiotherapy

2020 ◽  
pp. 030089162094420
Author(s):  
Dario Zerini ◽  
Filippo Patti ◽  
Francesca Spada ◽  
Nicola Fazio ◽  
Eleonora Pisa ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Multidisciplinary Approach ◽  
Unknown Primary ◽  
Team Approach ◽  
Merkel Cell ◽  
Limited Data ◽  
Free Survival ◽  
European Institute ◽  
Clinical Records

Objective: To review the therapeutic strategy in Merkel cell carcinoma (MCC) treated with radiotherapy (RT) discussed in a multidisciplinary tumour board. Methods: Clinical records of patients with a diagnosis of MCC and with an indication to undergo RT at the European Institute of Oncology between 2003 and 2018 were reviewed retrospectively. Results: Twenty-six patients were included in the analysis (median age 65 years, range 42–87). Nineteen received adjuvant RT, 4 exclusive RT, and the remainder palliative RT. Intensity-modulated RT was used in 13 cases, a 3D conformal technique in 11 cases, and stereotactic RT in 2 cases. No major toxicities were recorded. The median relapse-free survival (RFS) after adjuvant RT was 20.5 months, while for unknown primary MCC, it was 23 months. In the adjuvant setting, median polyomavirus-positive RFS was 21.5 months (range 1–49) and median polyomavirus-negative RFS was only 14 months (range 4–45). Overall, RFS of polyomavirus-positive and polyomavirus-negative patients was 10.5 and 8 months, respectively. After adjuvant RT, only 1 out of 10 patients had a recurrence in the RT field. At the time of data collection, 16 patients were alive with no evidence of disease, 1 patient was alive with advanced status of disease, 8 patients died of disease progression, and 1 patient died of other causes. Conclusions: The management of unknown primary and polyomavirus-positive cases, which had a better prognosis in our series, may benefit from a multidisciplinary approach, given the limited data available regarding optimal treatment.

scholarly journals Regionally Metastatic Merkel Cell Carcinoma Associated with Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sophia Z. Shalhout ◽  
Kevin S. Emerick ◽  
Peter M. Sadow ◽  
Jenny J. Linnoila ◽  
David M. Miller
Keyword(s):  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Psychiatric Symptoms ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Intensity Modulated Radiation Therapy ◽  
Sun Exposure ◽  
Merkel Cell ◽  
Paraneoplastic Encephalitis ◽  
Aspartate Receptor

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer with a high risk of recurrence and metastasis. MCC is generally associated with advanced age, fair skin, sun exposure, immunosuppression, and in the majority of cases, the Merkel cell polyomavirus. Neuroendocrine malignancies are associated with a variety of paraneoplastic neurological syndromes (PNS), characterized as autoimmune responses to malignancy-associated expression of neural antigens. Our literature review underscores previous case reports of MCC-associated PNS with voltage-gated calcium channel (VGCC) and anti-Hu (or ANNA-1) autoantibodies. We present the case of a 59-year-old male with regionally metastatic Merkel cell carcinoma complicated by the paraneoplastic manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. His primary lower neck subcutaneous MCC and metastasis were initially treated with surgery. Additional recurrent lymph node metastases were successfully treated with definitive intensity-modulated radiation therapy. His PNS improved with rituximab therapy. Although rare, this case highlights that in the setting of seizures and prominent psychiatric symptoms accompanying an MCC diagnosis, evaluation for autoimmune paraneoplastic encephalitis is warranted. Awareness and detection of preexisting PNS are crucial in the era of immune checkpoint inhibitors (ICI) for advanced MCC, where treatment with ICI has the potential to exacerbate preexisting autoimmune PNS and lead to worsened or even lethal neurologic immune-related adverse events (nirAEs).

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