Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy
Fuente:
Wiley Open Access
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Artículo Open Access |
| Published: |
Wiley
2025
|
| Subjects: | |
| Online Access: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1867018509558480896 |
|---|---|
| author | Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch |
| author_facet | Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch |
| collection | Wiley Open Access |
| contents | Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch Journal of the European Academy of Dermatology and Venereology Abstract 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. 10.1111/jdv.20708 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1111/jdv.20708 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_jdv_20708 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch Journal of the European Academy of Dermatology and Venereology Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy Katharina Schumann Kai Christian Klespe Cornelia Mauch Carmen Loquai Ulrike Schultheis Sevil Börger Alexander Thiem Steffen Emmert Magdalena Hoellwerth Peter Kölblinger Van Anh Nguyen Marina Wanner Erika Richtig Wiebke K. Peitsch Wolfgang Harth Veronika Zenderowski Andreas Dominik Braun Miriam Mengoni Reinhard Dummer Johanna Mangana Lara Valeska Maul Frank Meiß Klemens Rappersberger Oana Diana Persa Tilo Biedermann Christian Posch Journal of the European Academy of Dermatology and Venereology Abstract 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. 10.1111/jdv.20708 http://creativecommons.org/licenses/by/4.0/ |
| title | Switching PD‐1 to BRAF + MEK inhibition improves recurrence‐free survival in patients receiving a second course of adjuvant melanoma therapy |
| topic | Journal of the European Academy of Dermatology and Venereology |
| url | https://onlinelibrary.wiley.com/doi/10.1111/jdv.20708 |