Stopping Adjuvant Immunotherapy Early May Not Worsen Outcomes in Resected Metastatic Melanoma

Patients who receive adjuvant immunotherapy following metastatic melanoma resection do not experience inferior outcomes if they stop immunotherapy after less than 12 months, a new study has found. The study, which was published in the Journal of the European Academy of Dermatology and Venereology, suggests that patients who develop adverse events while taking adjuvant therapy may not benefit from continuing treatment.¹

Image Credit: © Ocskay Mark - stock.adobe.com

The study authors explained that patients with melanoma face a significant risk of recurrence following resection, particularly if they have distant metastatic melanoma.² Recurrence brings a high risk of mortality, depending on the cancer’s stage.

Anti–programmed cell death protein 1 (anti–PD-1) therapy has had a significant positive impact on outcomes for patients with metastatic melanoma, helping to decrease the risk of recurrence after resection. Yet, the authors noted it is unclear exactly how long adjuvant therapy should be continued. While recent trials have used a 12-month treatment duration, the reasoning behind the choice of 12 months as a treatment duration remains opaque.

Optimizing the length of time of adjuvant therapy is an important task, they argued, due to the “considerable risk for toxicity, including long-term side effects, time toxicity, and a financial burden for the health system or patients.”

The new study aimed to find out whether patients who discontinued immunotherapy due to toxicity have the same outcomes as patients who stay on therapy for the entire 12 months.

The investigators queried a multicenter skin cancer database to identify 620 patients with American Joint Committee on Cancer 8th edition stage III/IV resected melanoma who finished adjuvant treatment with either nivolumab (Opdivo) or pembrolizumab (Keytruda). The investigators then stratified patients based on whether they completed the entire course of therapy (52 ± 4 weeks) without recurrence, or whether they completed less than 48 weeks of therapy.

Nearly half of those who discontinued therapy early did so due to treatment-related side effects (45.3%), while the other half (54.7%) discontinued for reasons other than toxicity. The median treatment duration among those who stopped therapy early was 22.2 weeks, they said.

At a median follow-up of 26 months, participants who completed the entire course of immunotherapy or who experienced a recurrence while on adjuvant immunotherapy had a recurrence-free survival (RFS) rate of 51.5% (95% CI, 48.8-54.2). At a median follow-up of 19 months, patients who ended immunotherapy early had a 2-year RFS of 72.4% (95% CI, 68.5-76.3). When investigators excluded patients who experienced relapse during adjuvant treatment, the RFS for patients who completed the entire course of therapy was 84.1% (95% CI, 81.5-86.7).

The data show patients who terminated pembrolizumab or nivolumab earlier than 48 weeks for reasons other than disease progression did not have significantly inferior outcomes, according to the authors.

“According to our data, when toxicity leads to early termination, patients do not have a worse outcome than patients who discontinue adjuvant treatment for other reasons, and they may not benefit from continuation of adjuvant therapy,” they wrote.

When the investigators compared patients who experienced relapse after 12 weeks, there was a trend toward improved RFS in patients who were treated for the entire 12 months; however, there was no difference in overall survival.

The authors cited limitations due to factors associated with using a multicenter registry. For instance, reasons for longer treatment duration or premature discontinuation were not always listed in the data set. The investigators added that there was limited data on certain subsets of patients, such as patients with resected stage IV melanoma who received longer adjuvant therapy.

References

1. Tomsitz D, Livingstone E, Loquai C, et al. Early termination does not negatively impact the outcome of adjuvant immunotherapy in melanoma. J Eur Acad Dermatol Venereol. Published online March 22, 2025. doi:10.1111/jdv.20650
2. Leeneman B, Franken MG, Coupé VMH, et al. Stage-specific disease recurrence and survival in localized and regionally advanced cutaneous melanoma. Eur J Surg Oncol. 2019;45(5):825-831. doi:10.1016/j.ejso.2019.01.225

[This article was originally published by our sister publication, American Journal of Managed Care (AJMC).]