The Optimal Neoadjuvant Regimen of Checkpoint Inhibitors in High-Risk Melanoma Is Unclear

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Treatment with ipilimumab plus nivolumab in the neoadjuvant setting resulted in high patient response rates — but it was linked to high toxicity, as well.
Treatment with ipilimumab plus nivolumab in the neoadjuvant setting resulted in high patient response rates — but it was linked to high toxicity, as well.

A phase 2 study examining the neoadjuvant use of 2 regimens of immune checkpoint blockade in high-risk, resectable melanoma reinforced the need for more research in this area.1

The small study showed that neoadjuvant treatment with ipilimumab plus nivolumab resulted in high response rates with high toxicity, and treatment with single-agent nivolumab resulted in moderate response rates with low toxicity.

“Further studies are needed to optimize these regimens and determine long-term benefits as well as to better understand the mechanistic underpinnings of therapeutic response and resistance,” the researchers wrote.

Although studies have suggested an enhanced response to immune checkpoint inhibitors in the neoadjuvant setting, optimal treatment regimens have not been established.

In this study, researchers randomly assigned 23 patients to receive neoadjuvant nivolumab monotherapy or ipilimumab plus nivolumab. The overall response rate (ORR) was 25% for monotherapy compared with 73% for combination therapy.

“Responders demonstrated a trend towards a higher total mutational burden compared to nonresponders, although responses were seen even in patients with a low mutational burden,” the researchers noted.

Treatment with the combination also resulted in improved progression-free survival, relapse-free survival, distant-metastasis-free survival, and overall survival, but the differences compared with nivolumab monotherapy were not statistically significant.

Toxicity was significantly different between the 2 treatment groups. Only 8% of patients on monotherapy had grade 3 treatment-related adverse events compared with 73% of patients assigned to receive combination treatment.

The researchers noted that since the trial began, immune checkpoint blockade treatment dosing and schedules have been optimized.

Disclosure: This study was funded by a pharmaceutical company. For a full list of disclosures, please refer to the original study.

Reference

  1. Amaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma [published online October 8, 2018]. Nature Med. doi: 10.1038/s41591-018-0197-1

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