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

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Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG. / Haist, Maximilian; Stege, Henner; Rogall, Friederike; Tan, Yuqi; von Wasielewski, Imke; Klespe, Kai Christian; Meier, Friedegund; Mohr, Peter; Kähler, Katharina C; Weichenthal, Michael; Hauschild, Axel; Schadendorf, Dirk; Ugurel, Selma; Lodde, Georg; Zimmer, Lisa; Gutzmer, Ralf; Debus, Dirk; Schilling, Bastian; Kreuter, Alexander; Ulrich, Jens; Meiss, Frank; Herbst, Rudolf; Forschner, Andrea; Leiter, Ulrike; Pfoehler, Claudia; Kaatz, Martin; Ziller, Fabian; Hassel, Jessica C; Tronnier, Michael; Sachse, Michael; Dippel, Edgar; Terheyden, Patrick; Berking, Carola; Heppt, Markus V; Kiecker, Felix; Haferkamp, Sebastian; Gebhardt, Christoffer; Simon, Jan Christoph; Grabbe, Stephan; Loquai, Carmen.

In: J IMMUNOTHER CANCER, Vol. 11, No. 9, e007630, 09.2023.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Haist, M, Stege, H, Rogall, F, Tan, Y, von Wasielewski, I, Klespe, KC, Meier, F, Mohr, P, Kähler, KC, Weichenthal, M, Hauschild, A, Schadendorf, D, Ugurel, S, Lodde, G, Zimmer, L, Gutzmer, R, Debus, D, Schilling, B, Kreuter, A, Ulrich, J, Meiss, F, Herbst, R, Forschner, A, Leiter, U, Pfoehler, C, Kaatz, M, Ziller, F, Hassel, JC, Tronnier, M, Sachse, M, Dippel, E, Terheyden, P, Berking, C, Heppt, MV, Kiecker, F, Haferkamp, S, Gebhardt, C, Simon, JC, Grabbe, S & Loquai, C 2023, 'Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG', J IMMUNOTHER CANCER, vol. 11, no. 9, e007630. https://doi.org/10.1136/jitc-2023-007630

APA

Haist, M., Stege, H., Rogall, F., Tan, Y., von Wasielewski, I., Klespe, K. C., Meier, F., Mohr, P., Kähler, K. C., Weichenthal, M., Hauschild, A., Schadendorf, D., Ugurel, S., Lodde, G., Zimmer, L., Gutzmer, R., Debus, D., Schilling, B., Kreuter, A., ... Loquai, C. (2023). Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG. J IMMUNOTHER CANCER, 11(9), [e007630]. https://doi.org/10.1136/jitc-2023-007630

Vancouver

Haist M, Stege H, Rogall F, Tan Y, von Wasielewski I, Klespe KC et al. Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG. J IMMUNOTHER CANCER. 2023 Sep;11(9). e007630. https://doi.org/10.1136/jitc-2023-007630

Bibtex

@article{c76b52d162c54902b9b727806957b3ad,
title = "Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG",
abstract = "BACKGROUND: Adjuvant 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.METHODS: For this multicenter cohort study, we identified 515 BRAFmut 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.RESULTS: Among 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).CONCLUSIONS: BRAFmut 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.",
keywords = "Humans, Proto-Oncogene Proteins B-raf/genetics, Cohort Studies, Neoplasm Recurrence, Local/genetics, Prospective Studies, Skin Neoplasms/drug therapy, Melanoma/drug therapy, Registries, Adjuvants, Immunologic",
author = "Maximilian Haist and Henner Stege and Friederike Rogall and Yuqi Tan and {von Wasielewski}, Imke and Klespe, {Kai Christian} and Friedegund Meier and Peter Mohr and K{\"a}hler, {Katharina C} and Michael Weichenthal and Axel Hauschild and Dirk Schadendorf and Selma Ugurel and Georg Lodde and Lisa Zimmer and Ralf Gutzmer and Dirk Debus and Bastian Schilling and Alexander Kreuter and Jens Ulrich and Frank Meiss and Rudolf Herbst and Andrea Forschner and Ulrike Leiter and Claudia Pfoehler and Martin Kaatz and Fabian Ziller and Hassel, {Jessica C} and Michael Tronnier and Michael Sachse and Edgar Dippel and Patrick Terheyden and Carola Berking and Heppt, {Markus V} and Felix Kiecker and Sebastian Haferkamp and Christoffer Gebhardt and Simon, {Jan Christoph} and Stephan Grabbe and Carmen Loquai",
note = "{\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2023",
month = sep,
doi = "10.1136/jitc-2023-007630",
language = "English",
volume = "11",
journal = "J IMMUNOTHER CANCER",
issn = "2051-1426",
publisher = "BioMed Central Ltd.",
number = "9",

}

RIS

TY - JOUR

T1 - Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG

AU - Haist, Maximilian

AU - Stege, Henner

AU - Rogall, Friederike

AU - Tan, Yuqi

AU - von Wasielewski, Imke

AU - Klespe, Kai Christian

AU - Meier, Friedegund

AU - Mohr, Peter

AU - Kähler, Katharina C

AU - Weichenthal, Michael

AU - Hauschild, Axel

AU - Schadendorf, Dirk

AU - Ugurel, Selma

AU - Lodde, Georg

AU - Zimmer, Lisa

AU - Gutzmer, Ralf

AU - Debus, Dirk

AU - Schilling, Bastian

AU - Kreuter, Alexander

AU - Ulrich, Jens

AU - Meiss, Frank

AU - Herbst, Rudolf

AU - Forschner, Andrea

AU - Leiter, Ulrike

AU - Pfoehler, Claudia

AU - Kaatz, Martin

AU - Ziller, Fabian

AU - Hassel, Jessica C

AU - Tronnier, Michael

AU - Sachse, Michael

AU - Dippel, Edgar

AU - Terheyden, Patrick

AU - Berking, Carola

AU - Heppt, Markus V

AU - Kiecker, Felix

AU - Haferkamp, Sebastian

AU - Gebhardt, Christoffer

AU - Simon, Jan Christoph

AU - Grabbe, Stephan

AU - Loquai, Carmen

N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2023/9

Y1 - 2023/9

N2 - BACKGROUND: Adjuvant 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.METHODS: For this multicenter cohort study, we identified 515 BRAFmut 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.RESULTS: Among 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).CONCLUSIONS: BRAFmut 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.

AB - BACKGROUND: Adjuvant 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.METHODS: For this multicenter cohort study, we identified 515 BRAFmut 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.RESULTS: Among 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).CONCLUSIONS: BRAFmut 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.

KW - Humans

KW - Proto-Oncogene Proteins B-raf/genetics

KW - Cohort Studies

KW - Neoplasm Recurrence, Local/genetics

KW - Prospective Studies

KW - Skin Neoplasms/drug therapy

KW - Melanoma/drug therapy

KW - Registries

KW - Adjuvants, Immunologic

U2 - 10.1136/jitc-2023-007630

DO - 10.1136/jitc-2023-007630

M3 - SCORING: Journal article

C2 - 37730278

VL - 11

JO - J IMMUNOTHER CANCER

JF - J IMMUNOTHER CANCER

SN - 2051-1426

IS - 9

M1 - e007630

ER -