Multicenter real-world data of adjuvant treatment and disease outcome of patients with melanoma with high-risk of recurrence.

Livingstone, Elisabeth; Forschner, Andrea; Hassel, Jessica C.; Wulfken, Lena M.; Meier, Friedegund; Mohr, Peter G.; Kähler, Katharina C.; Schilling, Bastian; Loquai, Carmen; Berking, Carola; Hüning, Svea; Eckardt, Julia; Gutzmer, Ralf; Reinhardt, Lydia; Kowall, Bernd; Galetzka, Wolfgang; Hauschild, Axel; Zimmer, Lisa; Schadendorf, Dirk; Lodde, Georg

doi:10.1200/jco.2022.40.16_suppl.9570

Cited by 4 publications

(9 citation statements)

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“…The RFS and OS rates reported for BRAF/MEK-treated patients in this study are similar to the RFS and OS rates reported in the registration trials [15,37,38]. Livingstone et al described a recurrence rate of 35% in TT and 48% in ICI at a median follow-up time of 25.3 and 24.6 months, respectively, in resected stage III/IV melanoma patients registered into a central German registry [40]. Unfortunately, our data are based on shorter follow-up times, as BRAF/MEK-inhibition therapy was approved and reimbursed later in the Netherlands compared to Germany.…”

Section: Braf/mek-inhibition Therapy Toxicity Premature Treatment Ces...supporting

confidence: 87%

“…A recent follow-up study to the Lodde et al study by Livingstone et al reported similar real-world results to our present study. In their study, the authors showed slightly higher premature discontinuation rates (44%) in real-world patients treated with TT and showed that 60% of patients who prematurely discontinued treatment had done so due to toxicity [40]. The discrepancy in grade ≥3 adverse events rates and treatment discontinuation rates due to any grade adverse events might be due to the under-reporting of these events in daily clinical practice.…”

Section: Braf/mek-inhibition Therapy Toxicity Premature Treatment Ces...mentioning

confidence: 92%

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Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Meza

Blokx

Bonenkamp

et al. 2023

Cancers

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Adjuvant BRAF/MEK- and anti-PD-1 inhibition have significantly improved recurrence-free survival (RFS) compared to placebo in resected stage III BRAF-mutant melanoma. However, data beyond the clinical trial setting are limited. This study describes the toxicity and survival of patients treated with adjuvant BRAF/MEK inhibitors and compares outcomes to adjuvant anti-PD-1. For this study, stage III BRAF V600 mutant cutaneous melanoma patients treated with adjuvant BRAF/MEK-inhibition or anti-PD-1 were identified from the Dutch Melanoma Treatment Registry. BRAF/MEK- and anti-PD-1-treated patients were matched based on propensity scores, and RFS at 12 and 18 months were estimated. Between 1 July 2018 and 31 December 2021, 717 patients were identified. Of these, 114 patients with complete records were treated with BRAF/MEK therapy and 532 with anti-PD-1. Comorbidities (p = 0.04) and geographical region (p < 0.01) were associated with treatment choice. In 45.6% of BRAF/MEK-treated patients, treatment was prematurely discontinued. Grade ≥ 3 toxicity occurred in 11.5% of patients and was the most common cause of early discontinuation (71.1%). At 12 and 18 months, RFS in BRAF/MEK-treated patients was 85% and 70%, compared to 68% and 68% in matched anti-PD-1-treated patients (p = 0.03). In conclusion, comorbidities and geographical region determine the choice of adjuvant treatment in patients with resected stage III BRAF-mutant melanoma. With the currently limited follow-up, BRAF/MEK-treated patients have better RFS at 12 months than matched anti-PD-1-treated patients, but this difference is no longer observed at 18 months. Therefore, longer follow-up data are necessary to estimate long-term effectiveness.

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Section: Braf/mek-inhibition Therapy Toxicity Premature Treatment Ces...supporting

confidence: 87%

Section: Braf/mek-inhibition Therapy Toxicity Premature Treatment Ces...mentioning

confidence: 92%

Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Meza

Blokx

Bonenkamp

et al. 2023

Cancers

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“…Recently in ASCO Annual meeting, a multicenter real-world data of adjuvant treatment from German with 288 Stage III BRAF-mutant melanoma patients identified, also showed that risk of recurrence was higher and earlier for immunotherapy than for targeted therapy. 15 In their report, 1-year and 2-year RFS for adjuvant D + T was 88% and 66%, which was similar to the data from COMBI-AD. But for anti-PD1 immunotherapy, 2-year RFS declined to only 45%, which was much worse than 68% reported in KEYNOTE 054.…”

Section: Discussionsupporting

confidence: 69%

“…Our study suggested that in real‐world experience, for Chinese melanoma, adjuvant immunotherapy did not show a comparable benefit to adjuvant dual‐targeted therapy, which was similar to some other studies. Recently in ASCO Annual meeting, a multicenter real‐world data of adjuvant treatment from German with 288 Stage III BRAF‐mutant melanoma patients identified, also showed that risk of recurrence was higher and earlier for immunotherapy than for targeted therapy 15 . In their report, 1‐year and 2‐year RFS for adjuvant D + T was 88% and 66%, which was similar to the data from COMBI‐AD.…”

Section: Discussionsupporting

confidence: 59%

Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China

Zhong

Sun

et al. 2023

Cancer Medicine

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Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log‐rank analysis was used to identify prognostic factors for relapse‐free survival (RFS). Results Ninety‐three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti‐PD‐1 immunotherapy (PD‐1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation‐only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse‐free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD‐1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti‐PD‐1 monotherapy also showed significantly worse relapse control (p = 0.032). Conclusions For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse‐free survival compared to observation only. Dual‐targeted D + T therapy may still be the best choice for adjuvant therapy because anti‐PD‐1 monotherapy has failed to report equivalent efficacy in real‐world practice.

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“… 23 In line, a recent subgroup analysis by Lodde et al and a propensity matched analysis by Wouters et al reported that adjuvant DT showed superior RFS outcomes in a real-world cohort of resected melanoma patients when compared with adjuvant anti-PD1 therapy. 24 25 …”

Section: Discussionmentioning

confidence: 99%

Treatment management forBRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG

Haist,

Stege,

Rogall

et al. 2023

J Immunother Cancer

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BackgroundAdjuvant therapy with immune-checkpoint inhibitors (CPI) or BRAF/MEK-directed targeted therapy (TT) improves recurrence-free survival (RFS) for patients with advanced,BRAFV600-mutant (BRAFmut) resected melanoma. However, 40% of these patients will develop distant metastases (DM) within 5 years, which require systemic therapy. Little data exist to guide the choice of upfront adjuvant therapy or treatment management upon DM. This study evaluated the efficacy of subsequent treatments following tumor recurrence upon upfront adjuvant therapy.MethodsFor this multicenter cohort study, we identified 515BRAFmut patients with resected stage III melanoma who were treated with PD-1 inhibitors (anti-PD1) or TT in the adjuvant setting. Disease characteristics, treatment regimens, details on tumor recurrence, subsequent treatment management, and survival outcomes were collected within the prospective, real-world skin cancer registry ADOReg. Primary endpoints included progression-free survival (PFS) following DM and best tumor response to first-line (1L) treatments.ResultsAmong 515 eligible patients, 273 patients received adjuvant anti-PD1 and 242 adjuvant TT. At a median follow-up of 21 months, 54.6% of anti-PD1 patients and 36.4% of TT patients recurred, while 39.6% (anti-PD1) and 29.3% (TT) developed DM. Risk of recurrence was significantly reduced in patients treated with TT compared with anti-PD1 (adjusted HR 0.52; 95% CI 0.40 to 0.68, p<0.001). Likewise, median RFS was significantly longer in TT-treated patients (31 vs 17 months, p<0.001). Patients who received TT as second adjuvant treatment upon locoregional recurrence had a longer RFS2 as compared with adjuvant CPI (41 vs 6 months, p=0.009). Patients who recurred at distant sites following adjuvant TT showed favorable response rates (42.9%) after switching to 1L ipilimumab+nivolumab (ipi+nivo). Patients with DM during adjuvant anti-PD1 achieved response rates of 58.7% after switching to 1L TT and 35.3% for 1L ipi+nivo. Overall, median PFS was significantly longer in patients who switched treatments for stage IV disease (median PFS 9 vs 5 months, p=0.004).ConclusionsBRAFmut melanoma patients who developed DM upon upfront adjuvant therapy achieve favorable tumor control and prolonged PFS after switching treatment modalities in the first-line setting of stage IV disease. Patients with locoregional recurrence benefit from complete resection of recurrence followed by a second adjuvant treatment with TT.

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Multicenter real-world data of adjuvant treatment and disease outcome of patients with melanoma with high-risk of recurrence.

Cited by 4 publications

References 0 publications

Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China

Treatment management forBRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG

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