Faculty Opinions recommendation of Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

ABSTRACT Merkel cell carcinoma (MCC) is a rare and difficult-to-treat cutaneous malignancy with a poor prognosis. Treatment protocols for localized MCC are well established. Until recently, metastatic MCC has generally been treated with chemotherapy, which was often associated with poor clinical responses and significant toxicity. In this report, the case of a patient with metastatic MCC who received avelumab, an immune checkpoint inhibitor, after an inadequate response to first-line radiotherapy and chemotherapy, is presented. Nine months after the initiation of the treatment with avelumab, the patient achieved a partial remission with no treatment-related adverse events. After a follow-up of 17 months, a systematically ongoing partial response was reported. In conclusion, this case study offers a clinical insight into the patient’s case and highlights the importance of immunotherapy as a first-line therapy for metastatic MCC.

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

Journal of Clinical Oncology ◽

10.1200/jco.18.01896 ◽

2019 ◽

Vol 37 (9) ◽

pp. 693-702 ◽

Cited By ~ 102

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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Differences in terms of progression-free survival (PFS) and overall survival (OS) in patients treated with first-line sorafenib, sunitinib, and pazopanib for late relapsing (>5 years) renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.421 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 421-421

Author(s):

Matteo Santoni ◽

Camillo Porta ◽

Giuseppe Procopio ◽

Linda Cerbone ◽

Umberto Basso ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Univariate Analysis ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy

421 Background: Aim of this retrospective study was to investigate the clinico-pathological features and the outcome of patients (pts) with late relapsing renal cell carcinoma (LateR-RCC) treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) as first line therapy. Methods: Data were collected from 19 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 yr after initial radical nephrectomy. MSKCC prognostic categories were assessed before starting first-line treatment with VEGFR-TKI. Overall survival (OS) and progression free-survival (PFS) were estimated with the Kaplan-Meyer method with 95% CI and curves were compared with log-rank test. A Cox-regression model was applied to the data with a univariate and multivariate approach. Variables included in the univariate analysis were gender, age, time from surgery, MSKCC risk-group and targeted therapy employed at first line. Results: A total of 2,490 pts were screened and 269 pts (11%) were identified as LateR-RCC and treated with first-line VEGFR-TKI. Median age was 66 yr (range 29-87). Median time to recurrence was 7.9 yr. MSKCC prognostic category was good in 63% of pts, intermediate in 31% and poor in 6%. First-line therapy consisted of sunitinib in 190 pts (71%), sorafenib in 58 pts (21%) and pazopanib in 21 pts (8%). The median PFS was 20.0 months (95% CI 17.0−25.1) for sunitinib and 14.1 months for both sorafenib (95% CI 11.0−29.0) and pazopanib (95% CI 11.2−NR). At multivariate analysis, only MSKCC prognostic group was an independent prognostic factor for OS (HR: 2.07; 95% CI, 1.52–2.82 p < 0.001) and PFS (HR 2.54; 95% CI, 1.93−3.36 p < 0.001), whereas first line TKI was not significantly associated with OS (HR: 0.94; 95% CI, 0.38–1.82 p = 0.895) and PFS (HR 0.77; 95% CI, 0.43−1.99 p= 0.547). Conclusions: No significant differences were found in terms of OS and PFS in pts with LateR-RCC treated with first-line sorafenib, sunitinib or pazopanib. Our data may be considered in the long-term management of these patients.

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