Standard neoadjuvant immunotherapy in patients with resectable stage III melanoma – The early Australian experience

Author Identifier (ORCID)

Lydia Warburton’s ORCID record ORCID Logo

Abstract

Background: Neoadjuvant immune checkpoint inhibitor therapy (nICI) improves outcomes in stage III melanoma. Real-world data remain limited, especially in patient subgroups ineligible for trials or undergoing approaches deviating from trial protocols. Methods: Retrospective review of all patients who received nICI outside clinical trials for resectable stage IIIB-D melanoma across 8 Australian institutions. Baseline characteristics, treatment details, radiological and pathological responses, event-free survival (EFS) and recurrence-free survival (RFS) were examined. Results: From June 2023 to October 2025, 268 patients received nICI; 173 (65%) had lymph node (LN) metastases only, 65 (24%) had in-transit metastases (ITM) only, and 30 (11%) had both. Anti-PD-1 monotherapy (mono) was used in 198 patients (74%); 70 (26%) received anti-PD-1 + anti-CTLA-4 (combo). Surgery was performed in 227 patients (85%), while 41 (15%) did not proceed to surgery: 25 following clinical complete response (cCR), 14 due to progression, and 2 due to toxicity. Major pathological response (MPR) was achieved in 118 patients (52%). At a median follow-up of 12.1 months, combo was associated with higher 12-month EFS than mono (85.6% vs 75.6%, p ' 0.05). Patients with MPR to mono who omitted adjuvant ICI had lower 12-month RFS than those who received it (80.4% vs 100%, p ' 0.05); this difference was not observed after MPR to combo. ITM-only patients had similar 12-month EFS to LN-only patients (76.2% vs 81.0%, p = 0.13). No patient managed nonoperatively after cCR recurred. Conclusion: Neoadjuvant ICI is feasible in real-world practice, including for ITM-only disease. Following MPR to mono, adjuvant ICI confers superior outcomes than omitting it.

Keywords

adjuvant, immune checkpoint inhibitors, immunotherapy, in-transit metastases, gelanoma, neoadjuvant, nonoperative management, real-world

Document Type

Journal Article

Date of Publication

7-26-2026

Article Number

116865

ISSN

09598049

Volume

243

Publication Title

European Journal of Cancer

Publisher

Elsevier

School

Centre for Precision Health

RAS ID

99996

Funding Information

AMM is supported by an NHMRC Investigator Grant and Nicholas and Helen Moore. SNL have received funding from Melanoma Institute Australia. GVL is supported by an NHMRC Investigator Grant.

Copyright

subscription content

Content Type

Metadata only

Recommended Citation

Proulx-Rocray, F., Symons, R., Wang, Y., Liaqat, S., Warburton, L., Jiang, C., Wong, T., Hsiao, E., Ch’ng, S., Shannon, K. F., Rtshiladze, M., Pennington, T. E., Coker, D. J., Carlino, M. S., Spillane, A., Stretch, J., Saw, R. P., Van Akkooi, A. C., Snow, H., . . . Menzies, A. M. (2026). Standard neoadjuvant immunotherapy in patients with resectable stage III melanoma – The early Australian experience. European Journal of Cancer, 243, Article 116865. https://doi.org/10.1016/j.ejca.2026.116865

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Link to publisher version (DOI)

10.1016/j.ejca.2026.116865