Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial

Arance, Ana; Gogas, Helen; Dréno, Brigitte; Flaherty, Keith T.; Демидов, Лев В.; Stroyakovskiy, Daniil; Eroglu, Zeynep; Ferrucci, Pier Francesco; Pigozzo, Jacopo; Rutkowski, Piotr; Mackiewicz, Jacek; Rooney, Isabelle; Voulgari, Athina; Troutman, Sarah M.; Pitcher, Bethany; Yan, Yafei; Larkin, James

doi:10.1093/annonc/mdz394.066

Cited by 22 publications

(13 citation statements)

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“…The phase III IMspire 170 trial (NCT03273153) was designed to evaluate atezolizumab (PD-L1 inhibitor) plus cobimetinib (MEK inhibitor) versus pembrolizumab in untreated patients with BRAF wild-type tumors: unfortunately, it failed to meet its primary endpoint and PFS was not improved. 81 Recently, positive results were presented from a phase III triplet trial, IMspire150 (NCT02908672), in which cobimetinib plus vemurafenib was evaluated with or without atezolizumab in untreated patients with BRAF-mutant melanoma. The triplet combination significantly improved PFS compared with cobimetinib plus vemurafenib (15.1 vs 10.6 months), although objective response rates (ORRs) were similar; median OS data, although not mature, suggested a benefit with the triplet regimen.…”

Section: Long-term Survival Outcomesmentioning

confidence: 99%

Evolving impact of long-term survival results on metastatic melanoma treatment

Michielin

Atkins

Koon

et al. 2020

J Immunother Cancer

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Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

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Section: Long-term Survival Outcomesmentioning

confidence: 99%

Evolving impact of long-term survival results on metastatic melanoma treatment

Michielin

Atkins

Koon

et al. 2020

J Immunother Cancer

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“…Studies of ICIs with radiation are ongoing in a variety of cancers ( 21 , 33 ). ICIs combined agents targeting components of the MAP-kinase pathway have also been evaluated ( 21 , 34 – 36 ). Within the TME, vascular endothelial growth factor (VEGF)–driven angiogenesis is a key driver of tumor-associated immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Hack¹,

Zhu

Wang³

2020

Front. Immunol.

182

132

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“…These data, combined with our results, support a rationale for combining immunotherapy and MEKi in NRAS-mutated melanoma. However, the results of the IMspire 170 phase III trial comparing atezolizumab + cobimetinib to pembrolizumab in 450 patients with untreated BRAF WT melanoma proved negative [27]. The group of patients with BRAF WT and NRAS WT was too limited in size to be individually analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…While the combination with ipilimumab was too toxic [ 22 , 23 ], phase III clinical trials comparing the triple combination of anti-PD1 with dabrafenib + trametinib versus dabrafenib + trametinib + placebo (Keynote-022 [ 24 ], combi-I [ 25 ]), or the anti-programmed cell death ligand 1 (anti-PDL1) atezolizumab with vemurafenib + cobimetinib versus vemurafenib + cobimetinib + placebo (TRILOGY IMspire150 [ 26 ]) in treatment-naïve patients with BRAF V600-mutated advanced melanoma are ongoing. In BRAF WT melanoma, few data have been published to date about the combination of MEKi with anti-PD1 [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

Huynh

Mortier

Dutriaux³

et al. 2020

Cancers

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Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess the safety of combined ICI and TT as a rescue line in real-life clinical practice. We conducted a study within the prospective French multicentric MelBase cohort, including patients treated with a combination of anti-PD1 (pembrolizumab/nivolumab) and BRAF inhibitor (BRAFi: dabrafenib/vemurafenib) and/or MEK inhibitors (MEKi: trametinib/cobimetinib) for BRAF mutated or wild-type advanced melanoma. Fifty-nine patients were included: 30% received the triple combination, 34% an anti-PD1 and BRAFi, and 36% an anti-PD1 and MEKi. Grade 3–4 adverse events occurred in 12% of patients. Permanent discontinuation or dose reduction of one of the treatments for toxicity was reported in 14% and 7% of patients, respectively. In the BRAF wild-type subgroup, treatment with MEKi and anti-PD1 induced a tumor control rate of 83% and median progression-free survival of 7.1 months. The combination of anti-PD1 and BRAFi and/or MEKi was a safe rescue line for advanced melanoma patients previously treated with ICI/TT. The benefit of these combinations, specifically anti-PD1 and MEKi in BRAF wild-type melanoma patients, needs to be prospectively studied.

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Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (wt) advanced melanoma: Primary analysis from the phase III IMspire170 trial

Cited by 22 publications

References 0 publications

Evolving impact of long-term survival results on metastatic melanoma treatment

Evolving impact of long-term survival results on metastatic melanoma treatment

Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities

Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

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