Journal of the European Academy of Dermatology and Venereology : JEADV · 2025
Switching PD-1 to BRAF + MEK inhibition improves recurrence-free survival in patients receiving a second course of adjuvant melanoma therapy.
Clinical StudyСтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Schumann Katharina, Klespe Kai Christian, Mauch Cornelia, Loquai Carmen, Schultheis Ulrike, Börger Sevil, Thiem Alexander, Emmert Steffen, Hoellwerth Magdalena, Kölblinger Peter, Nguyen Van Anh, Wanner Marina, Richtig Erika, Peitsch Wiebke K, Harth Wolfgang, Zenderowski Veronika, Braun Andreas Dominik, Mengoni Miriam, Dummer Reinhard, Mangana Johanna, Maul Lara Valeska, Meiß Frank, Rappersberger Klemens, Persa Oana Diana, Biedermann Tilo, Posch Christian
Аннотация
BACKGROUND: PD-1 or BRAF + MEK inhibition is considered the current gold standard in adjuvant melanoma therapy. Little is known if, after the recurrence of the disease and surgery, a second course of adjuvant therapy might be beneficial.
METHODS: A multicenter, retrospective study investigating a second course of adjuvant therapy after recurrence and surgery in stage III-IV melanoma patients. Patients received nivolumab (NIV), pembrolizumab (PEM) or dabrafenib plus trametinib (D + T) between 01/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS2). Further analyses included descriptive and correlative statistics.
RESULTS: Sixty-six patients from 22 centers in Germany, Austria and Switzerland were included. Thirty-two patients received D + T as second-course adjuvant therapy, 9 patients received PEM and 25 patients received NIV. Recurrence-free survival for the second-course adjuvant treatment (RFS2) was assessed after 12 and 24 months and showed a superiority of adjuvant BRAF + MEK over PD-1 therapy (12-months RFS2: 90.6% vs. 70.6%, HR 4.226 [95% CI 1.154-15.48]; p = 0.030; 24-months RFS2 71.9% vs. 52.9%, HR 3.154 [95% CI 1.374-7.242]; p = 0.007). There was no significant decrease in OS with either BRAF + MEK or PD-1 treatment (12-months OS: 100% both, 24-months OS: 100% vs. 93.8%). Furthermore, therapy sequences were investigated. For better comparability, only BRAF V600 mutated patients were assessed: RFS2 was significantly better for patients with a class switch from PD-1 to BRAF + MEK compared to BRAF + MEK to PD-1 (HR 4.401 (1.04-18.63), p = 0.044). No new safety signals were detected.
CONCLUSIONS: In the investigated cohort, a second course of adjuvant melanoma treatment is feasible and provides similar RFS compared to an initial course of adjuvant therapy using BRAF + MEK inhibitors; however, RFS2 is reduced for PD-1 antibodies. In addition, both treatments were convincing with a 24-month OS of almost 100%. Switching from adjuvant PD-1 to BRAF + MEK treatment provided better overall RFS compared to switching from adjuvant BRAF + MEK to PD-1 treatment.
METHODS: A multicenter, retrospective study investigating a second course of adjuvant therapy after recurrence and surgery in stage III-IV melanoma patients. Patients received nivolumab (NIV), pembrolizumab (PEM) or dabrafenib plus trametinib (D + T) between 01/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS2). Further analyses included descriptive and correlative statistics.
RESULTS: Sixty-six patients from 22 centers in Germany, Austria and Switzerland were included. Thirty-two patients received D + T as second-course adjuvant therapy, 9 patients received PEM and 25 patients received NIV. Recurrence-free survival for the second-course adjuvant treatment (RFS2) was assessed after 12 and 24 months and showed a superiority of adjuvant BRAF + MEK over PD-1 therapy (12-months RFS2: 90.6% vs. 70.6%, HR 4.226 [95% CI 1.154-15.48]; p = 0.030; 24-months RFS2 71.9% vs. 52.9%, HR 3.154 [95% CI 1.374-7.242]; p = 0.007). There was no significant decrease in OS with either BRAF + MEK or PD-1 treatment (12-months OS: 100% both, 24-months OS: 100% vs. 93.8%). Furthermore, therapy sequences were investigated. For better comparability, only BRAF V600 mutated patients were assessed: RFS2 was significantly better for patients with a class switch from PD-1 to BRAF + MEK compared to BRAF + MEK to PD-1 (HR 4.401 (1.04-18.63), p = 0.044). No new safety signals were detected.
CONCLUSIONS: In the investigated cohort, a second course of adjuvant melanoma treatment is feasible and provides similar RFS compared to an initial course of adjuvant therapy using BRAF + MEK inhibitors; however, RFS2 is reduced for PD-1 antibodies. In addition, both treatments were convincing with a 24-month OS of almost 100%. Switching from adjuvant PD-1 to BRAF + MEK treatment provided better overall RFS compared to switching from adjuvant BRAF + MEK to PD-1 treatment.
Предметные рубрики MeSH
AdultAgedFemaleHumansMaleMiddle AgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantDisease-Free SurvivalImmune Checkpoint InhibitorsMelanomaNeoplasm Recurrence, LocalNivolumabOximesProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins B-rafPyridonesPyrimidinonesRetrospective StudiesSkin NeoplasmsImidazoles