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ESMO Immuno-Oncology 2018: OpACIN Trial: Neoadjuvant Ipilimumab Plus Nivolumab in Stage III Melanoma

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Key Points

  • After follow-up of median 31.6 months, none of the seven patients achieving a pathologic response in the neoadjuvant arm have relapsed.
  • The estimated 30-month RFS rate was 80% in the neoadjuvant arm.
  • 90% of patients developed one or more grade 3/4 adverse events; all of these patients recovered to ≤ grade 1, except for eight (50%) patients with ongoing endocrine toxicities, which required hormonal supplementation therapy.

Updated data of the OpACIN study, which studied combined ipilimumab (Yervoy) plus nivolumab (Opdivo) administered as neoadjuvant or adjuvant therapy in patients with high-risk stage III melanoma, demonstrated high response rates upon neoadjuvant therapy and promising long-term clinical outcome, according to findings presented by Rozeman et al at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2018 (Abstract LBA3).

Patients with high-risk stage III melanoma generally have a poor outcome, with less than 50% of patients surviving 5 years. Adjuvant ipilimumab has been shown to improve 5-year relapse-free survival (RFS) and overall survival (OS) rates, and RFS was improved even more with adjuvant anti–programmed cell death protein 1 (PD-1) therapy, according to study author Elisa A. Rozeman, MD, of The Netherlands Cancer Institute. In stage IV disease, the combination of ipilimumab plus nivolumab has been demonstrated to induce higher response rates. Therefore, Dr. Rozeman and colleagues conducted the phase Ib OpACIN feasibility trial to test this combination in stage III melanoma. 

Methods

From August 2015 to October 2016, the trial enrolled 20 patients with high-risk, stage IIIB/IIIC melanoma with palpable nodal disease. Patients were randomly assigned to receive ipilimumab at 3 mg/kg plus nivolumab at 1 mg/kg, either in four adjuvant courses, or to receive the same doses split into two neoadjuvant plus two adjuvant courses. Pathologic response was defined as < 50% viable tumor cells as reviewed by a blinded pathologist.

Findings

After follow-up of median 31.6 months (minimum = 23.5 months), none of the seven patients achieving a pathologic response in the neoadjuvant arm have relapsed. The two patients in this arm who did not achieve a pathologic response have relapsed. The estimated 30-month RFS rate was 80% in the neoadjuvant arm. The OS rate at 30 months was 90% with neoadjuvant treatment.

In the adjuvant arm, four patients have relapsed and the 30-month RFS rate was 60%. The 30-month OS rate with adjuvant treatment was 67%.

One patient in the neoadjuvant arm and three patients in the adjuvant arm died. At the time of the analysis, 16 patients were alive.

Ninety percent of patients developed one or more grade 3/4 adverse events; all of these patients recovered to ≤ grade 1, except for eight (50%) patients with ongoing endocrine toxicities, which required hormonal supplementation therapy.

The study authors concluded, “The OpACIN trial was the first trail initiated to investigate the combination of ipilimumab plus nivolumab as neoadjuvant treatment in patients with macroscopic stage III melanoma and, therefore, represents the longest follow-up of this regimen. None of the patients demonstrating pathologic response has relapsed, which suggested to the authors, that pathologic response could become a primary read-out for subsequent neoadjuvant immunotherapy trials, as well as a surrogate marker for RFS and OS.”

Disclosure: The study authors’ full disclosures can be found at academic.oup.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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