Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study

Ascierto, Paolo A.; Stroyakovskiy, Daniil; Gogas, Helen; Robert, Caroline; Lewis, Karl D.; Проценко, Светлана; Pereira, Rodrigo dos Santos; Eigentler, Thomas; Rutkowski, Piotr; Демидов, Лев В.; Zhukova, Natalia V.; Schachter, Jacob; Yan, Yibing; Caro, Ivor; Hertig, Christian; Xue, Cloris; Kusters, Lieke; McArthur, Grant A.; Gutzmer, Ralf

doi:10.1016/s1470-2045(22)00687-8

Cited by 54 publications

(38 citation statements)

References 23 publications

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“…In addition, the triplet regimen atezolizumab plus vem/cobi was approved in the USA in 2020. However, median OS in the second interim analysis was 39.0 months for the triplet therapy and 25.8 months for vem/cobi, which are not significantly different (HR: 0.84, p = 0.14) 64 . The National Comprehensive Cancer Network melanoma guidelines do not recommend the triplet regimen as first‐line treatment for BRAF‐mutated melanoma.…”

Section: Combination Therapy Of Icis and Braf/meki In Braf‐mutated Me...mentioning

confidence: 91%

“…However, median OS in the second interim analysis was 39.0 months for the triplet therapy and 25.8 months for vem/cobi, which are not significantly different (HR: 0.84, p = 0.14). 64 The National Comprehensive Cancer Network melanoma guidelines do not recommend the triplet regimen as first-line treatment for BRAF-mutated melanoma. In addition, a phase 3 study (COMBI-i) comparing the three-drug combination of the anti-PD-1 Ab spartalizumab plus dab/tra with dab/ tra failed to demonstrate a significant improvement of the primary endpoint, PFS.…”

Section: Comb Inati On Ther Apy Of I Cis and B R Af/mek I In B R Af-m...mentioning

confidence: 99%

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Optimal strategy in managing advanced melanoma

Uchi

2023

The Journal of Dermatology

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The advent of immune checkpoint inhibitors and combination therapy with BRAF inhibitors and MEK inhibitors has dramatically improved the prognosis of advanced melanoma. However, since acral melanoma and mucosal melanoma, which are rare in Western countries but are major subtypes of melanoma in East Asia, including Japan, have a low frequency of BRAF mutations, there are currently no treatment options other than immune checkpoint inhibitors in most such cases. Furthermore, owing to a lower tumor mutation burden, immune checkpoint inhibitors are less effective in acral and mucosal melanoma than in cutaneous melanoma. The aim of this review was to summarize the current status and future prospects for the treatment of advanced melanoma, comparing cutaneous melanoma, acral melanoma, and mucosal melanoma.

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Section: Combination Therapy Of Icis and Braf/meki In Braf‐mutated Me...mentioning

confidence: 91%

Section: Comb Inati On Ther Apy Of I Cis and B R Af/mek I In B R Af-m...mentioning

confidence: 99%

Optimal strategy in managing advanced melanoma

Uchi

2023

The Journal of Dermatology

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“…In the IMspire150 trial, a combination of vemurafenib plus cobimetinib (Vem/Cobi), a BRAF/MEKi, and atezolizumab, an anti‐PD‐L1 antibody, was compared with Vem/Cobi in 514 treatment‐naïve patients with advanced BRAF V600‐mutant melanoma. Although the investigator‐assessed PFS was prolonged in the triplet combination treatment arm, it was not confirmed by the central review, and OS was similar between the treatment arms 77–79 …”

Section: Emerging Combination Therapiesmentioning

confidence: 97%

“…Although the investigator-assessed PFS was prolonged in the triplet combination treatment arm, it was not confirmed by the central review, and OS was similar between the treatment arms. [77][78][79] In the RELATIVITY-047 trial, a fixed-dose combination of nivolumab plus relatlimab, (relatlimab-nivolumab), an anti-LAG-3 that for advanced melanoma. Given this, developing a new combination therapy by adding another agent to Nivo/Ipi seems difficult.…”

Section: Ta B L Ementioning

confidence: 99%

Long‐term survival with systemic therapy in the last decade: Can melanoma be cured?

Namikawa,

Nakano,

Ogata

et al. 2024

The Journal of Dermatology

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Immune checkpoint inhibitors have been shown to prolong survival of patients with several types of cancer, and the finding was first established in melanoma. Previously, systemic therapy for advanced melanoma aimed only at tumor control and palliation of symptoms. However, in recent years, some patients who received systemic therapy have achieved a complete response and survived without continuous treatment for more than several years. This review discusses the long‐term survival rates achieved with currently used systemic therapies and their future perspectives. Long‐term survival is currently most likely to be achieved with the use of the standard‐dose combination of nivolumab plus ipilimumab, however, this regimen is associated with a high frequency of serious or persistent immune‐related adverse events. Several new anti‐PD‐1‐based combination therapies with a better risk–benefit balance are currently under development. Although the acral and mucosal subtypes tend to be less responsive to immune checkpoint inhibitors, anti‐PD‐1‐based combination therapy should continue to be investigated for these subtypes owing to its potential for better long‐term survival. With the development of efficacious immunotherapy and targeted therapy, it is important to determine the optimal duration of systemic therapy to avoid unnecessary health and financial burdens as well as to improve efforts to support long‐term cancer survivors. As the goal of systemic therapy shifts from tumor control to long‐term survival, in future clinical trials, long‐term clinical outcomes should be evaluated to assess the benefits of novel agents.

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“…MAPK modulators in combination with immunotherapies could worsen gastrointestinal and dermal toxicities specifically, or increase the frequency of rarer effects such as neuropathies. A phase 3 trial (NCT02908672) combining atezolizumab (ant-PD-L1), cobimetinib (MEKi) and vemurafenib (BRAFi), observed toxicities of diarrhoea, nausea, rash and pyrexia, with some participants experiencing acute inflammation, and peripheral neuropathy (Table 1 ) [ 138 ]. Combinations with DDR1i and AXLi, are predicted to have a similar toxicity profile, with diarrhoea, nausea, rash and inflammation common [ 139 , 140 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer immune evasion through KRAS and PD-L1 and potential therapeutic interventions

Watterson

Coelho

2023

Cell Commun Signal

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Oncogenic driver mutations have implications that extend beyond cancer cells themselves. Aberrant tumour cell signalling has various effects on the tumour microenvironment and anti-tumour immunity, with important consequences for therapy response and resistance. We provide an overview of how mutant RAS, one of the most prevalent oncogenic drivers in cancer, can instigate immune evasion programs at the tumour cell level and through remodelling interactions with the innate and adaptive immune cell compartments. Finally, we describe how immune evasion networks focused on RAS, and the immune checkpoint molecule PD-L1 can be disrupted through therapeutic intervention, and discuss potential strategies for combinatorial treatment.

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Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study

Cited by 54 publications

References 23 publications

Optimal strategy in managing advanced melanoma

Optimal strategy in managing advanced melanoma

Long‐term survival with systemic therapy in the last decade: Can melanoma be cured?

Cancer immune evasion through KRAS and PD-L1 and potential therapeutic interventions

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