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

Rozeman, Elisa A.; Menzies, Alexander M.; Akkooi, Alexander C. J. van; Adhikari, Chandra Mani; Bierman, Carolien; Wiel, Bart A. van de; Scolyer, Richard A.; Krijgsman, Oscar; Sikorska, Karolina; Eriksson, Hanna; Broeks, Annegien; Thienen, J.V. van; Guminski, Alexander; Acosta, A. Torres; Meulen, Sylvia ter; Koenen, Anne Miek; Bosch, Linda J.W.; Shannon, Kerwin F.; Pronk, Loes M.; Gonzalez, Maria; Ch’ng, Sydney; Grijpink-Ongering, Lindsay G; Stretch, Jonathan R.; Heijmink, Stijn W. T. P. J.; Tinteren, Harm van; Haanen, John B.A.G.; Nieweg, Omgo E.; Klop, W. Martin C.; Zuur, Charlotte L.; Saw, Robyn P.M.; Houdt, Winan J. van; Peeper, Daniel S.; Spillane, Andrew J.; Hansson, Johan; Schumacher, Ton N.; Long, Georgina V.; Blank, Christian U.

doi:10.1016/s1470-2045(19)30151-2

Cited by 375 publications

(329 citation statements)

References 26 publications

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“…Nivolumab is indicated as an adjuvant treatment in all patients diagnosed with stage IIIA-IIID melanoma or totally resected stage IV melanoma. Nivolumab and ipilimumab combined treatment also shows promising results as neoadjuvant therapy in patients with macroscopic stage III melanoma [25].…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Nanosystems for Improved Targeted Therapies in Melanoma

Beiu

Giurcăneanu

Grumezescu

et al. 2020

JCM

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Melanoma is one of the most aggressive forms of skin cancer, with limited therapeutic options. Since its incidence has been rapidly rising in recent years, the study of new targeted therapeutic strategies has increased. The implication of nanoscience in the development of alternative targeted therapies for melanoma has multiple benefits and could significantly improve the outcome of melanoma patients. In this paper, we review the most recent progress in the field of targeted therapies, emphasizing the impact of nanoscale materials on the targeting and controlled release of anti-tumor drugs. The applications of nanomedicine in the management of melanoma are extensive and refer to sentinel lymph node mapping, chemotherapy, and RNA interference; each of these applications harboring the potential to develop efficient and personalized diagnostic techniques and therapies. Further research, especially in clinical trials, is needed to establish whether fighting melanoma on the nanoscale level represents the key to reaching a critical inflection point in mankind’s battle with metastatic melanoma.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Nanosystems for Improved Targeted Therapies in Melanoma

Beiu

Giurcăneanu

Grumezescu

et al. 2020

JCM

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“…This has even led to the formation of an International Neoadjuvant Melanoma Consortium which has recently published consensus-based recommendations on neoadjuvant systemic therapy [19]. Treatment approaches with both targeted (BRAF/MEK inhibitor combination) and immunotherapy have been investigated in the neoadjuvant setting [20][21][22][23][24][25]. The treatment duration before surgery typically ranged from 3 to 12 weeks in these trials, frequently followed by a period of adjuvant treatment resulting in a total treatment duration of 1 year.…”

Section: Neoadjuvant Treatmentmentioning

confidence: 99%

“…For example, after a median followup of 10 months, in 51 patients who achieved a pCR after neoadjuvant immunotherapy, not a single recurrence event had occurred. As toxicity is a particular issue with neoadjuvant combined immunotherapy, different dosing schedules have been compared in the largest neoadjuvant trial conducted to date (OpACINneo) [25]. A regimen with two cycles of ipi 1 mg/kg plus nivo 3 mg/kg before surgery without subsequent adjuvant therapy appeared to be most suitable for use in future neoadjuvant trials.…”

Section: Neoadjuvant Treatmentmentioning

confidence: 99%

Adjuvant and neoadjuvant treatment of melanoma

Koelblinger

2020

memo

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For years, interferon alpha was the sole option in the adjuvant treatment of patients with completely resected melanoma with lymph node metastases and a high risk of disease recurrence, albeit being associated with a relatively low efficacy combined with significant toxicities. After the advent of immunotherapy and targeted therapy in locally advanced or metastatic melanoma at the beginning of the last decade, these therapeutic approaches have meanwhile also shown superior efficacy compared to previously used treatments or observation in the context of adjuvant therapy. Hence, adjuvant targeted or anti-PD1-antibody-based immunotherapy was incorporated into routine clinical practice to reduce the risk of tumor recurrence in affected patients in early 2018. Moreover, modern melanoma therapies are increasingly being investigated in a neoadjuvant setting in analogy to other solid malignancies. Considering the promising results reported so far, neoadjuvant immunotherapy might potentially become the treatment of choice in high-risk melanoma patients with macrometastatic disease in the near future.

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“…Recently, neoadjuvant treatment schemes with ipilimumab and nivolumab were evaluated inducing a pathological response in a high proportion of patients after their surgery. 73 There are reasons to consider that neoadjuvant immunotherapy is even more promising than adjuvant therapy. The hypothesis is that with a melanoma tumor in situ, a stronger and broader tumor-specific T cell response can be achieved.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…And, according to the study of Rozeman et al, some patients may not require any surgery at all. 73 Studies to answer this question are now underway.…”

Section: Future Perspectivesmentioning

confidence: 99%