Haist, Maximilian;
Stege, Henner;
Ebner, Ronja;
Fleischer, Maria Isabel;
Loquai, Carmen;
Grabbe, Stephan
The Role of Treatment Sequencing with Immune-Checkpoint Inhibitors and BRAF/MEK Inhibitors for Response and Survival of Patients with BRAFV600-Mutant Metastatic Melanoma—A Retrospective, Real-World Cohort Study
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Medientyp:
E-Artikel
Titel:
The Role of Treatment Sequencing with Immune-Checkpoint Inhibitors and BRAF/MEK Inhibitors for Response and Survival of Patients with BRAFV600-Mutant Metastatic Melanoma—A Retrospective, Real-World Cohort Study
Beteiligte:
Haist, Maximilian;
Stege, Henner;
Ebner, Ronja;
Fleischer, Maria Isabel;
Loquai, Carmen;
Grabbe, Stephan
Erschienen:
MDPI AG, 2022
Erschienen in:
Cancers, 14 (2022) 9, Seite 2082
Sprache:
Englisch
DOI:
10.3390/cancers14092082
ISSN:
2072-6694
Entstehung:
Anmerkungen:
Beschreibung:
The advent of immune-checkpoint inhibitors (CPI) and BRAF/MEK-directed targeted therapy (TT) has improved the treatment landscape of patients with BRAFV600-mutant metastatic melanoma. While TT allows for rapid disease control, the development of secondary TT resistance limits the duration of responses. Responses to CPI have a slower onset but can be durable in a subset of patients. To date, little prospective data is available for the optimal sequencing of these agents in melanoma patients. In this retrospective, single-center, real-world analysis, we identified 135 patients with BRAF-mutated, metastatic melanoma who received consecutive treatment with TT followed by CPI, or vice versa, as first and second-line therapy, respectively. We collected data on clinical-pathological factors, treatment duration, best overall response, progression-free survival and overall survival (OS). Our data revealed that front-line treatment with CPI, followed by TT, showed a non-significant trend towards better OS compared to front-line TT (median OS: 35.0 vs. 18.0 months, p = 0.070). This association was confirmed in a subgroup of patients without systemic pre-treatments (median OS: 41.0 vs. 14.0 months, p = 0.02). Further, we observed significantly better objective response rates to second-line treatments for patients receiving front-line CPI (18.4 vs. 37.8%, p = 0.024). Last, our results indicated that rapid disease progression was less common in patients treated with front-line CPI (27.6% vs. 16.2%) and that subsequent treatment with TT resulted in favorable survival outcomes. Our real-world data indicate that sequential treatment with front-line CPI is associated with favorable tumor control and overall survival in a subgroup of previously untreated BRAF-mutant metastatic melanoma patients.