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Tumor Discovery Adjuvant immunotherapy in high-risk melanoma

individuals, with rates higher among males at 67/100,000 clinical trials that led to the regulatory approval of ICIs as
and slightly lower among females at 45/100,000, resulting adjuvant systematic treatments for resected Stage III and
in over 16,000 new cases, accounting for 11.2% of all newly IV melanoma. 12,13 In EORTC KN-054, pembrolizumab
diagnosed cancer cases. 2 (a monoclonal antibody against programmed death 1)
The American Joint Committee on Cancer (AJCC) was compared to placebo in resected high-risk Stage III
eighth edition melanoma staging system classifies patients melanoma patients. In the pembrolizumab group, the
into four prognostic stage groups categorized according to 12-month RFS rate was 75.4% (95% confidence interval
tumor size, lymph node involvement, and metastasis status. [CI]: 71.3 – 78.9) compared to 61.0% (95% CI: 56.5 – 65.1)
Stage III includes pathologically involved regional lymph in the placebo group. Treatment-related grade 3–5 toxicity
nodes and/or in-transit metastases. Furthermore, Stage III occurred in 14.7% of patients receiving pembrolizumab
has further substages – IIIA, IIIB, IIIC, and IIID – based on and 3.4% in the placebo group. Similarly, in CM-238,
the extent of regional lymph node involvement as well as nivolumab (a human IgG4 monoclonal antibody against
the status of the primary tumor lesion. Distant metastasis programmed death 1) demonstrated better RFS at the
is classified as a stage IV disease. Early detection is crucial, 12-month mark compared to ipilimumab in resected
3
as survival rates for melanoma significantly improve with high-risk Stage III and IV melanoma patients (70.5%
early-stage diagnosis. Five-year survival rates of Stages [95% CI: 66.1 – 74.5] vs. 60.8% [95% CI: 56.0 – 65.2],
IIIA, IIIB, IIIC, and IIID are 93%, 83%, 69%, and 32%, respectively). Nivolumab also exhibited lower toxicity
4
respectively. Surgical excision can be curative if melanoma compared to ipilimumab (14.4% vs. 45.9% for grade 3 – 4
5
is diagnosed at an early stage. However, some patients toxicity, respectively).
have metastatic disease at presentation. Many develop Beyond the clinical trial setting, there are limited data
metastatic disease after the initial, definitive surgical available on the outcomes of adjuvant systemic ICI therapy
treatment. in melanoma patients. Our study aimed to investigate
14
Over time, researchers have developed various the safety and efficacy of adjuvant systemic ICI therapy in
systemic therapies to treat patients with skin melanoma routine clinical practice for patients with resected Stage III
in an adjuvant setting. High-dose interleukin-2 (IL-2) and IV melanoma. We compared our findings with historical
was the first treatment introduced in the 1980s to data from key clinical trials such as the EORTC KN-054
change the disease course of metastatic melanoma in the and the CM-238 trial. Furthermore, we examined and
adjuvant setting, which led to some improvement in cure presented data on treatment efficacy, toxicity profiles, disease
rates; however, it was limited by severe toxicity. Later, recurrence rates, management strategies, and subsequent
6-8
biochemotherapy (chemotherapy combined with IL-2 treatment outcomes.
or interferon) improved the response rates but did not
translate into a better survival benefit. With innovation in 2. Methods
9
immune checkpoint inhibitors (ICIs) and targeted therapy, 2.1. Patients and procedures
the recurrence-free survival (RFS) and overall survival
(OS) of patients with resected malignant melanoma have Retrospectively, clinical data were collected for
improved, with a manageable toxicity profile. 95 patients treated with ICI therapy, that is, nivolumab or
pembrolizumab, between January 2018 and June 2021 at
The United States Food and Drug Administration the Medical Oncology Units of Fiona Stanley Hospital or
approved ipilimumab (a human immunoglobulin (G1) Hollywood Private Hospital.
monoclonal antibody against cytotoxic T-lymphocyte
antigen 4) in 2015 for adjuvant treatment in patients with The inclusion criteria comprised patients aged 18 years
resected Stage III melanoma. This approval was granted or older diagnosed with Stage III or Stage IV melanoma,
4
based on the improvement in RFS seen in the Phase 3 according to the 2018 AJCC eighth edition classification.
10
randomized, placebo-controlled trial. It was observed in All patients had an Eastern Cooperative Oncology Group
this clinical trial that at 5-year follow-up, the ipilimumab (ECOG) performance-status Score of 0–2 and histologically
resulted in better OS as compared to the placebo (65.4% confirmed melanoma with surgically resected metastases
vs. 54.4%), along with a better distant metastasis-free to regional lymph nodes or distant sites, indicating that
survival (DMFS), but with a toxicity profile of Grade 3 or 4 they were considered disease-free (Table 1).
immune-related adverse events of 42%. 11 All patients received standard care ICI regimens.
The European Organization for Research and Treatment Specifically, 87 patients were treated with intravenous
of Cancer (EORTC) 1325/KEYNOTE-054 trial (KN-054) infusions of nivolumab 480 mg every 4 weeks for up
and CheckMate-238 (CM-238) trial were the two landmark to 13 doses (or 240 mg every 4 weeks for 26 cycles),

Volume 3 Issue 3 (2024) 2 doi: 10.36922/td.3143