1. Nalley, Catlin

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Patients with stage III melanoma who received adjuvant immunotherapy had improved survival compared with those who did not, according to findings presented during the AACR Virtual Annual Meeting II, held June 22-24 (Abstract 4338).

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"Immune checkpoint inhibitors have significantly improved outcomes in clinical trials in melanoma," noted Justin Moyers, MD, a fellow at Loma Linda University in California. In 2015, the FDA approved ipilimumab as an adjuvant treatment to reduce the risk of melanoma recurrence. Subsequently, CheckMate 238 showed superior recurrence-free survival of nivolumab versus ipilimumab and was approved by the FDA in 2017.


"The goal of our study was to determine the percentage of patients receiving immunotherapy after surgery in the era of FDA approval for adjuvant checkpoint inhibitors following surgical resection in the real-world setting," Moyers said, in a statement. "We also aimed to see the 24-month survival rate of those receiving immunotherapy versus those who did not."


Study Details

Moyers and colleagues queried the National Cancer Database (NCDB) for treatment data from melanoma cases diagnosed in 2015 and 2016, as well as survival data from cases diagnosed in 2015. Eligible patients had stage III disease that was surgically resected. Researchers excluded those who received systemic therapies prior to surgery, as well as patients who underwent chemotherapy after surgery.


Patients were divided into two groups: receipt of immunotherapy or no receipt of immunotherapy after surgery. Investigators compared the following factors: age, sex, diagnosis year, pathologic stage group, Charlson-Deyo score, primary payer and state Medicaid expansion status, income, treatment region, and facility type.


Among all patients, the mean age was 60.3 years, according to Moyers. Those who did not receive immunotherapy were, on average, older at 62.4 years compared to 54.8 among those who received immunotherapy.


"Between 2015 and 2016, the percentage receiving immunotherapy increased from 24.8 percent to 30.6 percent," Moyers reported.


The percentage of patients receiving immunotherapy was similar regardless of insurance status at diagnosis, Moyers noted. The exception was Medicare with only 18.4 percent of patients receiving immunotherapy.


The study included 4,093 patients who met criteria to be analyzed for survival with 25 percent (n=1,014) receiving immunotherapy. Median overall survival has not yet been reached in either treatment group.


"Looking at survival for all stage III disease, the landmark 24-month survival was 83 percent for those receiving immunotherapy and 80 percent for those not receiving immunotherapy," Moyers reported. "When separating by substages, the survival differences between the immunotherapy received groups in stage IIIA and stage IIIC were found to be statistically significant."


For patients with stage IIIA disease who received immunotherapy, survival at 24 months was 94 percent compared to 91 percent for those who did not. Among patients with stage IIIC disease, survival was 70 percent for those who underwent immunotherapy versus 59 percent for those who did not receive any therapy after surgery.


Of the 8,160 patients who met the inclusion criteria for treatment pattern analysis, 28 percent (n=2,260) received adjuvant immunotherapy. The researchers reported that increasing Charlson-Deyo Scores of 1-3, lower income, lower high school graduation rate, 2015 as year of diagnosis, and Medicare as primary payer were associated with decreased percentage of patients receiving immunotherapy.


"There was a trend towards decrease in receipt of immunotherapy for those with lower income, and lower high school graduation rate (a measure of education), but this was not statistically significant," Moyers explained. "Based on our findings, immunotherapy after resected stage III melanoma appears to reveal a trend for real-world 24-month survival advantage compared with no therapy, supporting the role of adjuvant immunotherapy in the real-world setting."


NCBD is a retrospective cohort database, not a population database; therefore, Moyers acknowledged that there are limitations. Differences between specific agents used as immunotherapy cannot be assessed. Additionally, since the information is not reported to the database, disease-specific survival and recurrence/progression-free survival estimates cannot be made, he noted.


Some demographic data are based on averages from the zip codes of the patients' residence at diagnosis, and not specific to individual patients. "Additionally, we cannot differentiate between those who received adjuvant therapy versus palliative therapy after early progressive disease following surgery," Moyers added.


Conclusions, Ongoing Analysis

The researchers have provided the first early analysis of the NCDB in the era of adjuvant immune checkpoint inhibitors. This study showed a survival benefit for adjuvant immunotherapy in stage III melanoma at 24-month landmark analysis, although not yet statistically significant, Moyer said, adding this treatment did yield a superior survival advantage among resected stage IIIC melanoma patients.


Additionally, the study authors noted that sociodemographic factors appear to play a role in receiving adjuvant immunotherapy.


"This is an early analysis from the first year of adjuvant checkpoint inhibitor approval and should be repeated on data in subsequent years of follow-up to see if the survival curves show further separation as years progress," Moyers concluded.


"Dr. Moyers and colleagues analyze real-world data from the NCDB to study the use of adjuvant immunotherapy in patients with resected melanoma at high risk for relapse," commented Antoni Ribas, MD, PhD, FAACR, chairperson of the AACR Annual Meeting 2020 Program and AACR President, during the press briefing. "They analyze the data of over 8,000 patients, [focusing] on the year 2015 to 2016, which is the first year when adjuvant immunotherapy was approved for this indication following the reporting of improved outcomes in two large randomized trials, but the implementation of this therapy was low to start.


"Only one-third of patients received this therapy, but those patients did better than the ones who did not get adjuvant immunotherapy," he continued. "Patients with Medicare-only insurance and comorbid conditions were less likely to receive adjuvant immunotherapy and there was a trend for patients with lower income and lower high school graduation rates to also receive less adjuvant immunotherapy.


"Together, this data highlights the negative impact of socioeconomic background on having access to therapy that benefits patients, both in clinical trials and in real-world data," he concluded.


Catlin Nalley is a contributing writer.