Marco Donia, Professor at University of Copenhagen, shared a post on LinkedIn about a recent article by Georg C. Lodde et al, published in Journal of Clinical Oncology:
“Adjuvant PD-1 vs BRAF/MEK in Stage III Melanoma
Adjuvant therapy with anti-PD-1 or BRAF/MEK inhibitors (targeted therapy, TT) the only systemic option for patients with microscopic BRAF-mutant stage III melanoma.
n.b. Overall survival (OS) for anti-PD-1 vs observation still pending; BRAF/MEK did not show a statistically significant OS benefit.
This study compares real-world outcomes of patients treated with adjuvant anti-PD-1 vs TT. It does NOT compare active systemic treatment vs observation or discuss the value of RFS/median RFS.
Key Points
- Cohort and follow-up: 589 resected stage III melanoma, 11 German centers
- RFS at ~48 months (crude): PD-1 42.9% vs TT 52.6%; higher recurrence risk with PD-1 vs TT (HR 1.61, 95% CI 1.22–2.11).
- BRAF-mutant subset (n=232): higher recurrence risk with PD-1 vs TT (HR 1.57, 95% CI 1.09–2.26).
- Resected macroscopic disease: 1-year RFS 58% (PD-1) vs 87% (TT). All cohort: HR 1.65 (95% CI 1.00–2.73); in BRAF-mutant, HR 1.68 (95% CI 0.91–3.12).
Take-Home
- In this real-world series, TT was associated with lower recurrence risk than PD-1 at 4 year-follow up, particularly for early recurrences after resection of macroscopic disease.
Clinical Implications
- For BRAF-mutant stage III melanoma not receiving neoadjuvant therapy (and likely, for those with inadequate response to neoadjuvant immunotherapy), adjuvant TT remains an option to reduce early recurrence, especially after macroscopic nodal disease.
This is not a randomized study and is subject to the usual biases of, even well-conducted, real-world analyses.
The figures show RFS for BRAF mutant patients. Note the usual ‘banana’ shaped curves of RFS / PFS in BRAF/MEK (and many other targeted therapies), with curves becoming closer over time
These results are consistent with prior literature studies, such as Teresa Amaral, et al.”
Title: Long-Term Follow-Up of Real-World Adjuvant Anti–PD-1 Checkpoint Inhibition and Targeted Therapy in Patients With Stage III Melanoma
Authors: Georg C. Lodde, Jessica C. Hassel, Imke von Wasielewski, Friedegund Meier, Peter Mohr, Katharina Kähler, Axel Hauschild, Valerie Glutsch, Henner Stege, Carola Berking, Svea Hüning, Julia Huynh, Ralf Gutzmer, Lydia Reinhardt, Bastian Schilling, Carmen Loquai, Michael Erdmann, Andreas Stang, Bernd Kowall, Wolfgang Galetzka, Alexander Roesch, Daniel Tilkorn, Selma Ugurel, Lisa Zimmer, Dirk Schadendorf, Andrea Forschner, Elisabeth Livingstone
Read the Full Article on Journal of Clinical Oncology
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