scholarly journals Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up

ESMO Open ◽  
2021 ◽  
Vol 6 (6) ◽  
pp. 100290
Author(s):  
S.P. D'Angelo ◽  
S. Bhatia ◽  
A.S. Brohl ◽  
O. Hamid ◽  
J.M. Mehnert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Survival Data ◽  
Merkel Cell ◽  
Previously Treated

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.

scholarly journals Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma—A Retrospective Analysis of A Swedish Cohort

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 265
Author(s):  
Hannah Björn Andtback ◽  
Viveca Björnhagen-Säfwenberg ◽  
Hao Shi ◽  
Weng-Onn Lui ◽  
Giuseppe V. Masucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
University Hospital ◽  
Prognostic Impact ◽  
Merkel Cell ◽  
Hospital Data ◽  
Increased Risk ◽  
Significant Difference

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients’ hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future.

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]

scholarly journals Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy

2019 ◽  
Vol 37 (9) ◽  
pp. 693-702 ◽  
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Evan J. Lipson ◽  
William H. Sharfman ◽  
Ragini R. Kudchadkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
First Line ◽  
Median Response ◽  
Programmed Cell Death 1

PURPOSE Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus–positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1–positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION Here, we present the longest observation to date of patients with aMCC receiving first-line anti–programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

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