Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial

Mao, Lili; Ding, Ya; Bai, Xue; Sheng, Xinan; Dai, Jie; Chen, Zhihong; Cui, Chuanliang; Kong, Yan; Fan, Yun; Xu, Yanjun; Wang, Xuan; Tang, Bixia; Lian, Bin; Yan, Xieqiao; Li, Siming; Zhou, Li; Wei, Xiaoting; Li, Caili; Guo, Jun; Zhang, Xiaoshi; Si, Lu

doi:10.3389/fonc.2021.720044

Cited by 10 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With long-term follow-up of the Chinese patients identified in multicenter phase IIa trial for Dabrafenib plus Trametinib conducted in East Asia, ORR reached as 71.7% and PFS was 9.3 months, which was comparable to the data from the clinical trials with Caucasian population. 27 Our study still has several important limitations. First of all, it is a retrospective study with relatively small sample of patients in each treatment group.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 90%

“…With long‐term follow‐up of the Chinese patients identified in multicenter phase IIa trial for Dabrafenib plus Trametinib conducted in East Asia, ORR reached as 71.7% and PFS was 9.3 months, which was comparable to the data from the clinical trials with Caucasian population. 27 …”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…These results may imply that BRAF/MEK inhibitors can exert efficacy for acral melanoma (including NAM) comparable to that for cutaneous melanoma. Other case series may also support this notion [ 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ]. However, the long-term efficacy of targeted therapies remains unclear.…”

Section: Treatmentmentioning

confidence: 82%

“…A retrospective study from South Korea reported similar results (objective response rate of 78.9% in 10 acral/mucosal melanomas) [ 116 ]. Furthermore, a single-arm phase II trial in China (12 acral, 41 non-acral cutaneous, and 7 unknown primary melanomas) reported the efficacy of dabrafenib/trametinib combination therapy; the 3-year overall survival was 28.8% in the overall population and 35.7% in acral melanoma patients [ 117 ]. These results may imply that BRAF/MEK inhibitors can exert efficacy for acral melanoma (including NAM) comparable to that for cutaneous melanoma.…”

Section: Treatmentmentioning

confidence: 99%

Nail Apparatus Melanoma: Current Management and Future Perspectives

Ito

Hashimoto

Kaku-Ito

et al. 2023

JCM

View full text Add to dashboard Cite

Nail apparatus melanoma (NAM) is a rare type of cutaneous melanoma that belongs to the acral melanoma subtype. NAM is managed principally in accordance with the general treatment for cutaneous melanoma, but there is scarce evidence in support of this in the literature. Acral melanoma is genetically different from non-acral cutaneous melanoma, while recently accumulated data suggest that NAM also has a different genetic background from acral melanoma. In this review, we focus on recent advances in the management of NAM. Localized NAM should be surgically removed; amputation of the digit and digit-preserving surgery have been reported. Sentinel lymph node biopsy can be considered for invasive NAM for the purpose of accurate staging. However, it is yet to be clarified whether patients with metastatic sentinel lymph nodes can be safely spared completion lymph node dissection. Similar to cutaneous melanoma, immune checkpoint inhibitors and BRAF/MEK inhibitors are used as the first-line treatment for metastatic NAM, but data on the efficacy of these therapies remain scarce. The therapeutic effects of immune checkpoint inhibitors could be lower for NAM than for cutaneous melanoma. This review highlights the urgent need to accumulate data to better define the optimal management of this rare melanoma.

show abstract

“…[3][4][5] Immunotherapy (pembrolizumab, nivolumab, nivolumab plus ipilimumab, and nivolumab plus relatlimab) as a standard first-line therapy for advanced cutaneous melanoma 6 yields modest efficacy in advanced AM. [7][8][9][10][11] Despite the favorable efficacy of treatment with BRAF inhibitors combined with MEK inhibitors in patients with BRAF V600 -mutant advanced melanoma, 12,13 infrequent variants of BRAF (10%-22%) and NRAS (9%-28%) in AM limited the use of this combination. [3][4][5]14,15 KIT variants are primarily found in mucosal and acral melanomas, but also with a low frequency (10%-20%).…”

mentioning

confidence: 99%

Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

Mao

Lian

et al. 2023

JAMA Oncol

Self Cite

View full text Add to dashboard Cite

ImportanceAcral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking.ObjectiveTo investigate the activity and safety of camrelizumab (an anti–programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma.Design, Setting, and ParticipantsIn this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022.InterventionsPatients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m2, once daily on days 1 to 5 until disease progression or unacceptable toxic effects.Main Outcomes and MeasuresThe primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety.ResultsA total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years]) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%]), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%]). No treatment-related deaths occurred.Conclusions and RelevanceThe findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial.Trial RegistrationClinicalTrials.gov Identifier: NCT04397770

show abstract

Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial

Cited by 10 publications

References 29 publications

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

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

Nail Apparatus Melanoma: Current Management and Future Perspectives

Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

Contact Info

Product

Resources

About