Response rates and durability of chemotherapy among 62 patients with metastatic Merkel cell carcinoma

Abstract

Cytotoxic chemotherapy is commonly used to treat advanced Merkel cell carcinoma (MCC). However, its efficacy in distant metastatic MCC patients is unclear, in part because most prior reports aggregated these patients with those receiving adjuvant chemotherapy and combined chemoradiation for whom prognosis and outcomes may differ. In this retrospective study, we analyzed detailed records from 62 patients with distant metastatic MCC treated with cytotoxic chemotherapy. Efficacy outcomes including response rate (RR), durability of response (DOR), progression-free survival (PFS), and overall survival (OS) were evaluated. In this cohort, platinum plus etoposide was the most commonly used first-line regimen (69%). RR to first-line chemotherapy was 55% (34/62) with complete responses (CR) in 13% (8/62) and partial responses (PR) in 42% (26/62) while 6% (4/62) had stable disease and 39% (24/62) had progressive disease. Median PFS was 94 days and median OS was 9.5 months from start of chemotherapy. Among responding patients (n = 34), median PFS was 168 days and median DOR was 85 days. Among 30 of the 62 patients who received second-line chemotherapy, RR was 23% (7/30; 1 CR, 6 PR), median PFS was 61 days, and median DOR was 101 days. In summary, first-line chemotherapy is associated with a high RR in metastatic MCC, but responses are typically not durable, and the median PFS is only 3 months. These results suggest rapid emergence of chemoresistance in MCC tumors, and may serve as a useful comparator for immunotherapies currently being explored for metastatic MCC.

Keywords: Chemotherapy; Merkel cell carcinoma; durability of response; metastatic; neuroendocrine tumor; progression-free survival; response rate.

Figure 1

Response to first‐line chemotherapy. (A) Progression‐free survival (PFS) among all 62 patients with distant metastatic disease who received first‐line chemotherapy. (B) PFS is depicted among the patients based on their initial responses to first‐line chemotherapy.

Figure 2

Progression‐free survival in MCC patients following first‐line chemotherapy for distant metastatic disease. Table shows the immune status of each patient and their respective response to first‐line regimen. Platin plus etoposide was the most common first‐line chemotherapy in the study population. “Prior chemo” indicates patient had received previous adjuvant chemotherapy.

Figure 3

Progression‐free survival (PFS) in patients receiving second‐line chemotherapy, n = 30. (A) PFS among patients who received second‐line chemotherapy for distant metastatic MCC. (B) PFS from the time of initiation among patients who received second‐line chemotherapy. Median PFS was 61 days.

Figure 4

Overall survival in metastatic MCC, n = 62. (A) Overall survival from the time of initial diagnosis of distant metastatic disease. (B) Overall survival from the time of initiation of first‐line chemotherapy.