Adjuvant PD-1 Blockade in Resected Melanoma: Is Preventing Recurrence Enough?

Smithy, James W.; Shoushtari, Alexander N.

doi:10.1158/2159-8290.cd-21-1593

Cited by 7 publications

(12 citation statements)

References 8 publications

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“…In other recent trials evaluating adjuvant PD-1 antibodies (eg, CheckMate 238, SWOG S1404, and KEYNOTE-054), the lack of OS benefit despite RFS benefit raises questions of whether waiting for recurrence and receiving treatment for metastatic disease would be acceptable to patients. 5,[22][23][24] This is complicated by the active control arms in the two trials (CheckMate 238 and SWOG S1404) that have reported OS data thus far and the relative immaturity of those OS data. 5,22 Longer follow-up is needed for these trials to ascertain any long-term benefits with adjuvant PD-1 blockade.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Weber

Schadendorf²,

Vecchio

et al. 2023

JCO

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PURPOSE Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup. RESULTS At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.

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Section: Discussionmentioning

confidence: 99%

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Weber

Schadendorf²,

Vecchio

et al. 2023

JCO

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“…Therefore, a question of whether waiting for recurrence and receiving treatment for metastatic disease might be acceptable to patients was raised, and this may help avoid the risk of potentially irreversible immune-related adverse events in patients whose disease can be cured with surgery alone. 53 , 54 The oncologists need to discuss the known DFS benefits and the lack of OS benefit and side effects in the relatively short follow-up to date with the patient before making an adjuvant therapy decision. And assays like circulating tumor DNA (ctDNA), circulating tumor cells, tumor mutation burden (TMB), or exosome vesicles might be helpful in determining which patients are at a higher risk of disease recurrence after surgery.…”

Section: Discussionmentioning

confidence: 99%

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis

Zhu

Zhang

et al. 2023

Ther Adv Med Oncol

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Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III–IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III–IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

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“…Prior to 2015, interferon-α 2b was the only approved agent for adjuvant treatment of patients with high-risk cutaneous melanoma [ 115 , 116 , 117 , 118 ]. Interferon-α-2b exhibits anti-tumour activity by enhancing natural-killer cell activity as well as tumour antigen presentation and has been shown to have anti-proliferation and anti-angiogenic effects [ 115 ].…”

Section: The Era Of Immunotherapymentioning

confidence: 99%

The Evolution of the Sentinel Node Biopsy in Melanoma

Allard-Coutu

Dobson

Schmitz

et al. 2023

Life

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The growing repertoire of approved immune-checkpoint inhibitors and targeted therapy has revolutionized the adjuvant treatment of melanoma. While the treatment of primary cutaneous melanoma remains wide local excision (WLE), the management of regional lymph nodes continues to evolve in light of practice-changing clinical trials and dramatically improved adjuvant therapy. With large multicenter studies reporting no benefit in overall survival for completion lymph node dissection (CLND) after a positive sentinel node biopsy (SLNB), controversy remains regarding patient selection and clinical decision-making. This review explores the evolution of the SLNB in cutaneous melanoma in the context of a rapidly changing adjuvant treatment landscape, summarizing the key clinical trials which shaped current practice guidelines.

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Adjuvant PD-1 Blockade in Resected Melanoma: Is Preventing Recurrence Enough?

Cited by 7 publications

References 8 publications

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis

The Evolution of the Sentinel Node Biopsy in Melanoma

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