Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: Updated results from a phase III trial (CheckMate 238).

Weber, Jeffrey S.; Mandalà, Mario; Vecchio, Michele Del; Gogas, Helen; Arance, Ana; Cowey, C. Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Rodas, Iván Márquez; Grob, Jean‐Jacques; Butler, Marcus O.; Middleton, Mark R.; Maio, Michele; Atkinson, Victoria; Dummer, Reinhard; Pril, Veerle de; Qureshi, Anila; Larkin, James; Ascierto, Paolo A.

doi:10.1200/jco.2018.36.15_suppl.9502

Cited by 62 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adjuvant anti-PD-1, nivolumab has very recently shown a significant RFS benefit for stage IIIB/C, IV (AJCC seventh edition; [43]) resected melanoma when compared with adjuvant high-dose ipilimumab, with an RFS HR of 0.66, 70% of patients free of relapse versus 60% at 12 months, 66% versus 53% at 18 months and 63% versus 50% at 24 months, respectively [55]. The RFS HR is very consistent across stage subgroups with 0.68 for IIIB, 0.68 for IIIC and 0.66 for M1a/M1b [55]. Moreover, this adjuvant treatment with nivolumab had far fewer grade 3/4 adverse events compared with the very toxic high-dose ipilimumab; 14.4% versus 45.9%, respectively [56].…”

Section: Special Articlementioning

confidence: 99%

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Michielin¹,

et al. 2019

View full text Add to dashboard Cite

Section: Special Articlementioning

confidence: 99%

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Michielin¹,

et al. 2019

View full text Add to dashboard Cite

“…The 1 year recurrence-free survival rates were 70.5% in the nivolumab arm and 60.8% in the ipilimumab arm. At a minimum follow-up of 24 months, recurrence-free survival rates continued to be higher for nivolumab vs. ipilimumab with 62.6% vs. 50.2% [38]. Toxicity was lower in the nivolumab arm with adverse events requiring therapy discontinuation in 9.7% of patients compared with 42.6% of patients in the ipilimumab arm.…”

Section: Adjuvant Therapymentioning

confidence: 91%

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Gellrich

Schmitz

Beissert

et al. 2020

JCM

101

View full text Add to dashboard Cite

Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).

show abstract

“…Some preclinical models suggested that neoadjuvant therapy with clinically detectable volumes of disease would be required to induce long‐term disease control . These preclinical concerns surrounding an overt tumor microenvironment being a requirement for anti‐PD1 activity have been settled in melanoma, however, with the reporting of multiple international adjuvant therapy clinical trials of completely resected stage IIIB and IIIC (AJCCv7) and stage IV disease (Table ) . In the CheckMate 238 study (Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIB/IIIC or Stage IV Melanoma) of stage III and IV melanoma (stages IIIB and IIIC, resected stage IV; AJCCv7), nivolumab demonstrated superiority to ipilimumab in terms of both relapse‐free survival (RFS) and toxicity profile.…”

Section: Role Of Anti‐pd1 Therapy In Melanomamentioning

confidence: 99%

“…20 These preclinical concerns surrounding an overt tumor microenvironment being a requirement for anti-PD1 activity have been settled in melanoma, however, with the reporting of multiple international adjuvant therapy clinical trials of completely resected stage IIIB and IIIC (AJCCv7) and stage IV disease (Table 1). [21][22][23][24][25] In the CheckMate 238 study (Efficacy Study of Nivolumab Compared to Ipilimumab in Prevention of Recurrence of Melanoma After Complete Resection of Stage IIIB/IIIC or Stage IV Melanoma) of stage III and IV melanoma (stages IIIB and IIIC, resected stage IV; AJCCv7), nivolumab demonstrated superiority to ipilimumab in terms of both relapse-free survival (RFS) and toxicity profile. Similarly, in the KEYNOTE-054 study (Study of Pembrolizumab [MK-3475] Versus Placebo After Complete Resection of High-Risk Stage III Melanoma, pembrolizumab demonstrated superiority to placebo in patients with completely resected stage III melanoma (stages IIIA, IIIB, and IIIC; AJCCv7).…”

Section: Role Of Anti-pd1 Therapy In Melanomamentioning

confidence: 99%

Considering adjuvant therapy for stage II melanoma

Poklepovic

Luke

2019

Cancer

View full text Add to dashboard Cite

Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier stage at diagnosis. Before 2011, treatment options were limited for patients with metastatic disease, and the median overall survival was less than 1 year. Since then, the field of melanoma therapeutics has undergone major changes. The use of anti–CTLA‐4 and anti‐PD1 immune checkpoint inhibitors and combination BRAF/MEK inhibitors for patients with BRAF V600 mutations has significantly extended survival and allowed some patients to remain in durable disease remission off therapy. It has now been confirmed that these classes of agents have a benefit for patients with stage III melanoma after surgical resection, and anti‐PD1 and BRAF/MEK inhibitors are standards of care in this setting. Some patients with stage II disease (lymph node‐negative; American Joint Committee on Cancer stage IIB and IIC) have worse melanoma‐specific survival relative to some patients with stage III disease. Given these results, expanding the population of patients who are considered for adjuvant therapy to include those with stage II melanoma has become a priority, and randomized phase 3 clinical trials are underway. Moving into the future, the validation of patient risk‐stratification and treatment‐benefit prediction models will be important to improve the number needed to treat and limit exposure to toxicity in the large population of patients with early stage melanoma.

show abstract

Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: Updated results from a phase III trial (CheckMate 238).

Cited by 62 publications

References 0 publications

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Considering adjuvant therapy for stage II melanoma

Contact Info

Product

Resources

About