Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE)

Orlova, Kristina V.; Ledin, Evgeniy V; Zhukova, Natalia V.; Орлова, Р. В.; Карабина, Е. В.; Volkonsky, Mikhail; Stroyakovskiy, Daniil; Yurchenkov, Aleksandr N; Проценко, Светлана; Novik, A.V. Novik; Vorotilina, Ludmila V; Moiseenko, Fedor; Chang, V L; И, Казьмин А; Tkachenko, Svetlana A; Gamaunov, Sergey V; Насхлеташвили, Д. Р.; Samoylenko, Igor; Vikhrova, Anastasia S; Utyashev, Igor; Kharkevich, G Yu; Петенко, Н. Н.; Шубина, И. Ж.; Демидов, Лев В.

doi:10.3390/cancers13112529

Cited by 16 publications

(10 citation statements)

References 28 publications

(32 reference statements)

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“…Analyses performed excluding these patients led to the same results (data not shown). Previous real-world research showed a statistically significant difference in PFS and OS for different V600 mutations [19]. In the real-world population, subsequent anticancer therapy was used in 52% of the patients, which was comparable to data from the COMBI-v and -d trial (53%) and the coBrim trial (51%) [5,17].…”

Section: Trials Vs Real-worldsupporting

confidence: 67%

Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

et al. 2022

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Recent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS) of more than 2 years. This study aimed to investigate these patients' real-world survival and identify the characteristics of long-term survivors. The study population consisted of patients with advanced cutaneous melanoma with a BRAF-V600 mutated tumor who were treated with first-line BRAF-MEK inhibitors between 2013 and 2017. Long-term survival was defined as a minimum OS of 2 years from start therapy. The median progression-free survival (mPFS) and median OS (mOS) of real-world patients (n = 435) were respectively 8.0 (95% CI, 6.8-9.4) and 11.7 (95% CI, 10.3-13.5) months. Two-year survival was reached by 28% of the patients, 22% reached 3-year survival and 19% reached 4-year survival. Real-world patients often had brain metastases (41%), stage IV M1c disease (87%), ECOG PS ≥2 (21%), ≥3 organ sites (62%) and elevated LDH of ≥250 U/I (49%). Trial-eligible real-world patients had an mOS of 17.9 months. Patients surviving more than 2 years (n = 116) more often had an ECOG PS ≤1 (83%), normal LDH (60%), no brain metastases (60%), no liver metastases (63%) and <3 organ sites (60%). Long-term survival of realworld patients treated with first-line BRAF-MEK inhibitors is significantly lower than that of trial patients, which is probably explained by poorer baseline characteristics of patients treated in daily practice. Long-term survivors generally had more favorable characteristics with regard to age, LDH level and metastatic sites, compared to patients not reaching longterm survival. Melanoma Res 32: 460-468

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Section: Trials Vs Real-worldsupporting

confidence: 67%

Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

et al. 2022

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“…In the 382 included patients the ORR to the combined BRAF/MEK inhibitor and to the BRAF inhibitor mono-therapy were 57.4% and 39.8%, respectively. The median PFS and OS were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third or higher-line therapy [12]. The results of this study were similar to those in clinical trials and better than those in other real-world data studies.…”

Section: Discussionmentioning

confidence: 97%

Real-world treatment patterns and outcomes in patients with metastatic melanoma

et al. 2023

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Introduction/Objective. The purpose of this study was to assess the effectiveness of different approaches in the treatment of metastatic melanoma in daily clinical practice in a situation with limited and late availability of new drugs in a resource-limited country and to compare these parameters with those reported in clinical studies and from other real-world data. Methods. Main methods included assessment of overall survival (OS) and progression-free survival (PFS). Patients were included in the study if they were treated with first or second-line systemic therapy for radiologically/pathologically confirmed metastatic melanoma. Patients were divided into four groups based on the type of therapy they received: chemotherapy (dacarbazin), BRAF inhibitor (vemurafenib), BRAF/MEK inhibitors (vemurafenib/cobimetinib and trametinib/dabrafenib) and anti PD-1 therapy with pembrolizumab. Results. Regardless of the line of therapy, the calculated median OS in chemotherapy and vemurafenib group was nine months. The median OS in the BRAF/MEK inhibitor group was 14 months and 15 months in the pembrolizumab group. Median PFS in the chemotherapy group was four months, seven months for vemurafenib, in the BRAF/MEK inhibitor group nine months and in the pembrolizumab group six months. There was a statistically significant difference in survival between first and second-line therapy in the pembrolizumab group. Conclusion. Our results showed lower median OS and PFS in comparison to reported data from clinical trials. Compared to other real-world data from countries with similar problems related to the late reimbursement of new drugs, our research has shown similar results.

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“…BRAFi plus MEKi combination therapy has demonstrated improved efficacy compared with BRAFi alone and is the standard TT option for patients with BRAF+ melanoma, which could explain the difference in findings between this study and ours. Moreover, this sequencing analysis included a small number of patients ( n = 123), with only 31 patients in the IO before TT group and 92 patients in the IO after TT group, and it was unclear whether this analysis was adjusted for baseline differences between groups [14].…”

Section: Discussionmentioning

confidence: 99%

“…One other study by Orlova et al . [14] found that patients who received IO (anti-PD1) before TT demonstrated a significantly higher survival rate compared to those who started IO after TT. The TT group in this study, however, included both patients who received BRAF inhibitor (BRAFi) monotherapy and those who received BRAFi plus MEK inhibitor (MEKi) combination therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Atkins et al [13] compared patients likely to receive one of two treatment sequences, 1L IO/2L TT or 1L TT/2L IO, in advanced BRAF+ melanoma patients and found no difference in OS after adjusting for differences in demographics and confounding factors. One other study by Orlova et al [14] found that patients who received IO (anti-PD1) before TT demonstrated a significantly higher survival rate compared to those who started IO after TT. The TT group in this study, however, included both patients who received BRAF inhibitor (BRAFi) monotherapy and those who received BRAFi plus MEK inhibitor (MEKi) combination therapy.…”

Section: Relation To Prior Workmentioning

confidence: 98%

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Real-world outcomes of different lines and sequences of treatment in BRAF-positive advanced melanoma patients

et al. 2022

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The objective of this study is to compare efficacy with different treatment sequences and lines of treatment among BRAF V600 mutated (BRAF+) advanced melanoma patients with immunotherapies (IO) and targeted therapies (TT) using real-world data. This was a retrospective cohort study using the Novartis BRAF+ meLanoma patients ObsErvational database, the harmonized customized data from Flatiron and ConcertAI. The study included BRAF+ advanced unresectable melanoma patients treated with first-line (1L) IO or TT between 1 January 2014 and 31 May 2020. Patient characteristics and treatment patterns were described. Kaplan–Meier curves and propensity score-adjusted Cox models were used for analyzing progression-free survival (PFS) and overall survival (OS). A total of 1961 patients were included, of which, 57.2% received IO and 42.8% received TT on 1L therapy. Overall, 603 patients initiated a 2L therapy: 56.2% IO and 43.8% TT. Regardless of treatment sequence, patients progressed at a relatively similar rate with no significant difference between groups (median PFS: 12.9 months for 1L TT/2L IO and 13.1 months for 1L IO/2L TT; HR, 0.84; P = 0.137). The 2-year OS rate was also similar with 1L TT/2L IO and 1L IO/2L TT (78% vs. 80%; HR, 1.09; P = 0.730). PFS was worse on 2L therapy compared with 1L (median 4.7 vs. 6.5 months). Efficacy on 2L therapy was poor compared with 1L. Among patients who received 2L therapy, regardless of treatment sequences, outcomes were comparable between 1L TT/2L IO and 1L IO/2L TT in this study that reflects real-world experiences beyond clinical trial selective eligibility criteria.

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Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE)

Cited by 16 publications

References 28 publications

Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Real-world treatment patterns and outcomes in patients with metastatic melanoma

Real-world outcomes of different lines and sequences of treatment in BRAF-positive advanced melanoma patients

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