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.

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

“…Despite these limitations, the results from this study are consistent with those of a recent retrospective analysis of patients with distant mMCC who received 2L chemotherapy, which reported an ORR of 23% and median PFS of 2 months [12]. Similar to the results reported here, the DOR was short (median DOR of 3.3 months [range: 0.2-7.4 months]).…”

“…Treatments typically include platinum agents, such as carboplatin or cisplatin with or without etoposide or topotecan, and are associated with high toxicity [9,11]. Although MCC is generally considered a chemosensitive tumor, responses to chemotherapy in metastatic disease are often not durable: response rates in the secondline (2L) setting range from 23% in patients with known distant metastasis to 45% in patients with unclear (nodal and/or distant) sites of metastasis [12,13]. In the first-line (1L) or mostly 1L setting, response rates range from 53 to 61% [12][13][14][15][16][17].…”

“…Regardless of the line of therapy, disease reoccurs in most patients by 6 months [12,14,17]. The available data are insufficient to assess the effect of chemotherapy on OS.…”

Nonprogression with Avelumab Treatment Associated with Gains in Quality of Life in Metastatic Merkel Cell Carcinoma

“…This is in line with the fact that most AEs related to avelumab were low grade, consisting mostly of fatigue and infusion-related reaction. Taken together, this indicates that avelumab is well tolerated and that its safety profile was manageable, whereas previous studies in patients with mMCC treated with chemotherapy have shown high rates of significant toxicities [8][9][10][11].…”

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

“…Although virtually all patients are initially rendered free of detectable disease, roughly half of these patients will recur [95,96]. Once distant metastatic disease arises, cytotoxic chemotherapy leads to a response in >50% of cases, but the median time to progression is only 3 months and durable responses are exceedingly rare [97]. There is thus an urgent need for improved therapies.…”