Real-World Study Demonstrates Benefits with Adjuvant Nivolumab in Resected Stage IIIA Melanoma

A significant proportion of patients with resected stage IIIA melanoma were alive and recurrence-free after a median follow-up of more than 20 months after treatment with adjuvant nivolumab (Opdivo), according to a real-world analysis presented at the 19th International Congress of the Society for Melanoma Research.1

Patients treated with adjuvant nivolumab (n=171) achieved a 12-month disease-free survival rate (FRS) of 97.1% (95% CI, 93.1% to 98.8%) versus 81.6 % (95% CI, 65.2% to 90.8%) for patients who were observed (n=38). RFS rates at 18 months were 91.4% (95% CI, 85.6% to 94.9%) versus 78.6% (95% CI, 61.6% to 88.7%) , respectively. The median RFS was not reached in either arm.

Additionally, neoadjuvant nivolumab treatment improved overall survival (OS) rates at 12 and 18 months; 98.2% (95% CI, 94.6%-99.4%) and 94.2% (95% CI, 89.1%-96.9%) compared to 94.7% (CI at 95%, 80.6%-98.7%) and 91.8% (95% CI, 76.6%-97.3%) in the observation group, respectively. Median OS was 34.6 months and not achieved, respectively.

“In 2 published real-world studies, nivolumab was shown to provide benefit, but the numbers were small,” Anna C. Pavlick, BSN, MSc, DO, MBA, medical oncologist at Weill Cornell Medicine, in New York, New York, said in a data presentation. “Therefore, we present the actual Cardinal Health database [for patients] with resected stage IIIA melanoma treated with nivolumab or observation. It is the largest real-world database to be presented to date. »

The real-world study collected data from Cardinal Health’s extensive network of proprietary oncology providers. 2017.3 However, according to the AJCC-7 staging criteria, patients with stage IIIA melanoma were excluded and a minimal number of AJCC-8 patients were recruited.

Patients in the adjuvant nivolumab cohort (n=171) and an observation cohort were ≥18 years of age with AJCC-8 stage IIIA melanoma and underwent complete surgical resection between Jan. 2018 and December 31, 2019.2

The mean age of the patients was 57.4 years in the adjuvant nivolumab cohort and 68.1 years in the observation group; both cohorts had a predominantly white male population. Year to resection was 30% in 2018 and 70% in 2019 compared to 47% in 2018 and 53% in 2019, respectively.

Most patients in both cohorts had 1 node involvement, but 33% of patients in the nivolumab arm had 2 or 3 node involvement versus 26% in the observation arm. Only 1 patient had 4 or more and was in the nivolumab arm.1

In patients for whom data were known or available, most patients in both groups had a sentinel lymph node tumor mass of 1 mm to 4 mm. Primary lesion sites were similar across cohorts: trunk (25% vs 24%), extremities (55% vs 53%), head/neck (20% vs 21%), and external genitalia (1% vs 3% ), in the nivolumab and observation groups, respectively. Although ulcers were mostly absent, 22% of patients in the nivolumab arm and 18% of patients in the observation arm had ulcers. The median Breslow thickness of the tumors at the time of resection was 1.80 vs 1.90, respectively. ECOG performance status ranged from 0 to 3, with most patients scoring 0.

The median duration of treatment with nivolumab was 12.0 months (95% CI, 11.8-12.0). Three patients continued treatment and 91% of patients completed the planned duration of nivolumab treatment, with the most common reasons for discontinuation being patient choice, toxicity, and disease progression.

Additional data from the study showed that distant metastasis-free survival was also examined and was 98.2% and 91.3% versus 94.7% and 88.8%, respectively.

The median time to first recurrence was 18.9 (range, 3.9-29.1) months in the nivolumab arm and 9.4 months (range, 2.6-30.6) in the observation, the most common sites being the lungs and lymph nodes. A first recurrence occurred in 11% versus 26% of patients, respectively. There were 11 deaths (6%) in the nivolumab group and 6 deaths (16%) in the observation group and the most common cause was disease progression. Cardiovascular diseases, infectious diseases and unspecified diseases were also cited as fatal events.1

With respect to safety, treatment-related endocrine, dermatological, gastrointestinal, and hepatic adverse events (TREIs) of any grade occurred in the adjuvant nivolumab group at rates of 13%, 11%, 8%, and 5 %, respectively. Grade 3 or 4 events were observed in the endocrine and gastrointestinal categories in 1% and 2% of patients, respectively, and 2% of patients discontinued treatment due to EITR. The data was collected from patient records and may be underreported because the data is real-world, the investigators noted.

Although the study used a national database to assess real-world data from this subgroup of patients who may be able to provide a more precise date than data from the randomized controlled trial population, the The analysis was retrospective. Other limitations included the shorter follow-up of survival outcome data, as patients with stage IIIA melanoma have a relatively good prognosis, errors that may have occurred in data entry, and differences in baseline characteristics of the cohort.

A lack of adjustment for heterogeneity between the 2 cohorts when reporting Kaplan-Meier curves was a challenge, the study authors wrote.

When asked if removing the IIIA from patients by less than 1mm would result in curves more like what one would expect, Pavlick explained: “The number of measurements that have been done, it there are very few patients who have had a numerical measurement in their sentinel lymph node [and because] it was mostly reported as positive or negative, which would be hard to do.

References

  1. Pavlick AC, Amin A, Moser JC, et al. Results in patients with resected stage IIIA melanoma treated with adjuvant nivolumab or followed up with observation: a real-life study. Presented at: 19th International Congress of the Society for Melanoma Research. October 17-20, 2022. Edinburgh, Scotland.
  2. Pavlick AC, Amin A, Moser JC, et al. Results in patients with resected stage IIIA melanoma treated with adjuvant nivolumab or followed up with observation: a real-life study. J Clin Oncol. 2022;40(supplement 16): e21534. doi:10.1200/JCO.2022.40.16_suppl.e21534
  3. The FDA grants regular approval to nivolumab for the adjuvant treatment of melanoma. FDA. December 20, 2017. Accessed November 7, 2022. bit.ly/3WYnDe6

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