Toxicity of combined targeted therapy and concurrent radiotherapy in metastatic melanoma patients: a single-center retrospective analysis

Ziegler, Johanna S; Kroeze, S.G.C.; Hilbers, Marie-Luise; Imhof, Laurence; Gückenberger, Matthias; Levesque, Mitchell P.; Dummer, Reinhard; Cheng, Phil F.; Mangana, Joanna

doi:10.1097/cmr.0000000000000682

Cited by 5 publications

(1 citation statement)

References 42 publications

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“…For this combination, mainly an increased risk of skin toxicity has been described in the literature [ 21 ]. Although the study of Hecht et al observed an increased risk in grade ≥2 toxicity and worse OS when BRAFi was continued during SRT due to its radiosensitizing properties, the study of Ziegler et al did not see these side-effects when BRAFi was combined with MEKi [ 30 , 31 ], with the hypothesis that MEKi can mitigate the occurrence of skin side effects [ 32 ]. In this study, we did not observe skin toxicity since the dose to the skin is usually limited with SRT.…”

Section: Discussionmentioning

confidence: 99%

Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis

Kroeze

Fritz

Schaule

et al. 2021

Cancers

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The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan–Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1–102 mo); 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11–40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1–42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare; a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation.

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Section: Discussionmentioning

confidence: 99%

Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis

Kroeze

Fritz

Schaule

et al. 2021

Cancers

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Systemic Treatment of Melanoma

Dummer,

Goldinger

2024

Rook's Textbook of Dermatology

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Systemic therapy for melanoma patients has dramatically improved over the past decade. New treatment strategies have significantly ameliorated survival and prognosis of affected patients. The indication for immune directed and targeted therapies has expanded and can be considered for both very early melanoma stages as well as advanced disease. Ongoing challenges deal with reducing development of primary and secondary resistance to antitumoural drugs and identifying useful biomarkers as well as improving quality of life of affected patients. Overall, the aim to cure metastatic melanoma has become more tangible than ever before.

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Which is the best treatment for melanoma brain metastases? A Bayesian network meta-analysis and systematic review

Li,

Zhong

et al. 2024

Critical Reviews in Oncology/Hematology

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Toxicity of combined targeted therapy and concurrent radiotherapy in metastatic melanoma patients: a single-center retrospective analysis

Abstract: Supplemental Digital Content is available in the text.

Cited by 5 publications

References 42 publications

Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis

Continued versus Interrupted Targeted Therapy during Metastasis-Directed Stereotactic Radiotherapy: A Retrospective Multi-Center Safety and Efficacy Analysis

Systemic Treatment of Melanoma

Which is the best treatment for melanoma brain metastases? A Bayesian network meta-analysis and systematic review

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