Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma
February 20, 2025
Journal
European Journal of Cancer
Publication Date
February 20, 2025
Authors
Merkelcell.org Summary
Merkel cell carcinoma (MCC) is a rare but aggressive type of skin cancer that can spread beyond where it first appears. In the past, chemotherapy was the main treatment for MCC that had spread, but immunotherapy—where the body’s own immune system is boosted to fight cancer—has significantly improved survival rates.
This study looked at 158 patients with metastatic MCC from 17 cancer centers across six countries to understand how they responded to immunotherapy. About 60% of patients saw their tumors shrink completely or partially, and on average, their response lasted 43 months. However, not all patients had lasting benefits—59% of patients had their cancer worsen, typically around 14 months after starting treatment. This included those whose cancer initially responded as above but later progressed (secondary resistance, 50%) and those whose cancer never responded to immunotherapy at all (primary resistance, 26%).
Out of 50 patients whose cancer worsened on immunotherapy, 18 switched to chemotherapy, while 16 continued with immunotherapy—either the same or a different type—combined with other treatments. Among those who tried chemotherapy, 67% had some tumor shrinkage, but it only lasted around five months. On the other hand, 56% of patients who received another round of immunotherapy combined with other treatments saw benefits that lasted about 20 months.
These findings highlight two key takeaways: Immunotherapy is generally effective for treating metastatic MCC. For patients whose cancer worsens, continuing immunotherapy along with other treatments may offer relatively long-lasting benefits.
Abstract
Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.
Method: This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy.
Results: One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median follow-up of 28.7 months (95 % CI: 21.4-38.3), ORR was 57.3 %, median DOR was 42.8 months (95 % CI, 25.8 – not reached (NR)), median PFS was 14 months (95 % CI, 8.1- 19.8), and median OS was 42.8 months (95 % CI, 30.3 – NR). One-hundred and eight patients (59 %) experienced progressive disease; 50 % (n = 54/108) with primary resistance and 26 % (n = 28/108) with secondary resistance. Fifty patients (27 %; n = 50/185) received subsequent systemic therapies (+/- local therapy) with response data; 18 (36 %; n = 18/50) received doublet platinum chemotherapy (ORR 67 %, DOR 5.0 months [95 % CI; 3.7 – NR]) and 16 (32 %; n = 16/50) were rechallenged with anti-PD-(L)1 (ORR 56 %, DOR 20.2 months [95 % CI; 8.3 – NR]).
Conclusion: The most common subsequent treatment for patients with primary resistance was chemotherapy, while those with secondary resistance most frequently underwent further anti-PD-(L)1 therapy in combination with other therapies. Despite both therapies demonstrating promising ORR, doublet platinum chemotherapy had a poorer DOR compared to anti-PD-(L)1 rechallenge.
Keywords: Carcinoma; Immune Checkpoint Inhibitors; Immunotherapy; Merkel Cell; Neoplasms; Skin.
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