- •Response to neoadjuvant therapy is concordant in the primary site and nodal melanoma.
- •Neoadjuvant therapy induces high response rates in the primary site and nodal melanoma.
- •Consider postponing resection of the primary site melanoma to after neoadjuvant therapy.
Patients with synchronous clinical stage III melanoma can present with primary melanoma lesions, locally recurrent melanoma or in-transit metastases. Neoadjuvant ipilimumab plus nivolumab induces high pathologic response rates and an impressive relapse-free survival in patients with nodal macroscopic stage III melanoma. Whether primary site melanoma and in-transit metastases respond similarly to lymph node metastases with neoadjuvant immunotherapy is largely unknown. Such data would clarify whether surgical excision of these melanoma lesions should be performed before neoadjuvant therapy or whether it could be deferred and performed in conjunction with lymphadenectomy following neoadjuvant immunotherapy.
Patients with synchronous clinical stage III melanoma were identified from the OpACIN, OpACIN-neo and PRADO neoadjuvant trials, where all patients were treated with ipilimumab plus nivolumab. An additional case treated outside those clinical trials was included.
Seven patients were identified; six patients had a concordant response in primary site melanoma lesions or in-transit metastasis and the lymph node metastases. One patient had concordant progression in both the primary and nodal tumour lesions and developed stage IV disease during neoadjuvant treatment, and thus, no resection was performed.
Pathologic response following neoadjuvant ipilimumab plus nivolumab in primary site melanoma lesions or in-transit metastasis is concordant with a response in the lymph node metastases, indicating that there may be no need to perform upfront surgery to these melanoma lesions prior to neoadjuvant treatment.
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- Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual.CA – Cancer J Clin. 2017; 67: 472-492
- Adjuvant pembrolizumab versus placebo in resected stage III melanoma.N Engl J Med. 2018; 378: 1789-1801
- Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma.N Engl J Med. 2017; 377: 1824-1835
- Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma.N Engl J Med. 2017; 377: 1813-1823
- Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma.Nat Med. 2018; 24: 1655-1661
- Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.Lancet Oncol. 2019; 20: 948-960
- 1313PD 3-year relapse-free survival (RFS), overall survival (OS) and long-term toxicity of (neo)adjuvant ipilimumab (IPI) + nivolumab (NIVO) in macroscopic stage III melanoma (OpACIN trial).Ann Oncol. 2019; 30: v535
- LBA75 18-months relapse-free survival (RFS) and biomarker analyses of OpACIN-neo: a study to identify the optimal dosing schedule of neoadjuvant (neoadj) ipilimumab (IPI) + nivolumab (NIVO) in stage III melanoma.Ann Oncol. 2019; 30: v910
- Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.N Engl J Med. 2003; 349: 859-866
- Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer.N Engl J Med. 2012; 366: 299-309
- Preoperative chemoradiotherapy for esophageal or junctional cancer.N Engl J Med. 2012; 366: 2074-2084
- Melanoma patients with unknown primary site or nodal recurrence after initial diagnosis have a favourable survival compared to those with synchronous lymph node metastasis and primary tumour.PloS One. 2013; 8e66953
- Neoadjuvant immunotherapy with combined ipilimumab and nivolumab in patients with melanoma with primary or in transit disease.Br J Dermatol. 2020 Sep; 183: 559-563
- Personalized response-driven adjuvant therapy after combination ipilimumab and nivolumab in high-risk resectable stage III melanoma: PRADO trial.J Clin Oncol. 2019; 37 (TPS9605-TPS9605)
- Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma.Ann Oncol. 2018; 29: 1861-1868
- Mitotic rate and subcutaneous involvement are prognostic factors for survival after recurrence in patients with only locoregional skin metastasis as the first site of recurrence from cutaneous melanoma.J Eur Acad Dermatol Venereol. 2013; 27: 436-441
- Learning from clinical trials of neoadjuvant checkpoint blockade.Nat Med. 2020; 26: 475-484
- First safety and efficacy results of PRADO: a phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma.J Clin Oncol. 2020; 38 (10002–10002)
- Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.Nat Med. 2018; 24: 1649-1654
- A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma.Nat Med. 2019; 25: 454-461
Published online: March 15, 2021
Accepted: February 3, 2021
Received in revised form: December 18, 2020
Received: September 18, 2020
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