Highlights
- •An exploratory analysis was performed on 84 survival curves from 26 clinical trials in advanced metastatic melanoma.
- •In first-line, BRAF plus MEK inhibition was superior to PD-1 plus/minus CTLA-4 blockade within the first 12 months.
- •After 12 months, checkpoint blockers revealed superiority in the long-term survival.
- •In second-line or higher, BRAF plus MEK inhibition was superior to anti-PD-1 monotherapy throughout the first three years.
Abstract
Background
Recent therapeutic strategies, particularly MAP kinase pathway inhibitors (BRAF, MEK)
and immune checkpoint blockers (CTLA-4, PD-1), have been put on the test for their
differential impact on long-term survival of metastatic melanoma patients. Various
agents, dose regimens and combinations have been tested against each other vigorously
within these two therapy groups. However, results from prospective head-to-head comparative
trials comparing both strategies against each other are still lacking.
Methods
We performed an exploratory analysis of survival data from selected clinical trials
representative for these two treatment strategies in advanced metastatic melanoma.
84 Kaplan–Meier survival curves from 26 trials were digitised and grouped by therapy
strategy and treatment line. For each of these groups, mean survival curves were generated
for progression-free (PFS) and overall survival (OS) by weighted averaging.
Results
Survival curves grouped together by therapy strategy revealed a high concordance,
with a larger extent in the first-line setting compared to higher treatment lines.
In first-line therapy, the averaged 3-year OS proportions were 41.3% for BRAF plus
MEK inhibition, 49.9% for PD-1 inhibition, and 58.4% for CTLA-4 plus PD-1 inhibition.
Comparison of the mean PFS and OS curves of kinase inhibition and checkpoint blockade
revealed a superiority of combined BRAF plus MEK inhibition within the first 12 months,
later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4
blockade. In second-line or higher, BRAF plus MEK inhibition was superior to anti-PD-1
monotherapy throughout the first three years; averaged 3-year OS proportions were
42.4% for BRAF plus MEK inhibition, and 40.1% for PD-1 inhibition.
Conclusions
and relevance: These results need confirmation by head-to-head comparative randomised
clinical trials.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 13, 2020
Accepted:
February 2,
2020
Received:
January 30,
2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
