1. Objective response rate was not significantly different in patients treated with stereotactic body radiotherapy compared to those without.
2. Partial response was seen in 100% of ICI-naïve patients compared to 31% of patients with prior ICI treatment.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Current treatment standards include immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-PD-L1 monotherapy. This study evaluated combination treatment with nivolumab and ipilimumab with or without stereotactic body radiotherapy (SBRT). Enrolled patients were randomly assigned to combination treatment with or without SBRT and were stratified based on previous ICI use. Objective response rate (ORR) was highest in ICI-naïve patients with 100% achieving a partial response and 41% achieving complete response. Objective response rate was lower in the ICI-relapsed or ICI-refractory population, but still clinically meaningful. ORR was not significantly different between patients treated with SBRT and those without SBRT. The most common treatment-related adverse event was fatigue. There were three deaths, but these were attributed to disease progression and not treatment. Limitations of this study include the relatively small sample size, given the rarity of the disease. Nevertheless, this study supports the use of combination nivolumab and ipilimumab for those with recurrent and metastatic Merkel cell carcinoma.
In-Depth [randomized controlled trial]: In this phase 2 study, participants were enrolled if they were at least 18 years old and had a diagnosis of unresectable, recurrent or stage IV Merkel cell carcinoma. Patients were required to have two histologically proven tumour lesions to assess the response of the irradiated lesion. A total of 50 participants were randomized 1:1 to either nivolumab and ipilimumab (group A, n = 25) or nivolumab and ipilimumab plus SBRT (group B, n = 25). Treatment regimens were nivolumab 240 mg every 2 weeks, IV ipilimumab 1 mg/kg every 6 weeks, and group B received SBRT at a dose of 24 Gy during week 2. All patients had a CT thorax, abdomen and pelvis at the time of screening and every 12 weeks. The scans were evaluated using the immune-related Response Evaluation Criteria in Solid Tumours (irRECIST) which was used to determine treatment response. The median follow-up period was 14.6 months. No significant differences in ORR were seen between group A and group B (72% vs 52%, p=0.26). A total of 22 of 22 (100%) of the ICI-naïve patients had an objective response and nine of 22 (41%) had a complete response. A total of eight of 26 (31%) of the previous ICI patients had an objective response and four of 26 (15%) had a complete response. Adverse events (grade 3 or 4) were seen in 10 of 25 (40%) patients in group A and 8 of 25 (32%) in group B.
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