Checkpoint blockade and BRAF/MEK therapy in the therapeutic setting improved the overall survival after sentinel node biopsy: A retrospective study comparing patients with primary care between 1998‐2009 and 2010‐2017
Immunotherapies using checkpoint blockade and BRAF/MEK therapies have improved overall survival (OS) in patients with unresectable melanoma metastases. In this retrospective study, we aimed to demonstrate the resulting increase in melanoma‐specific survival (MSS) and OS after the excision of primary...
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| Published in: | International journal of cancer Vol. 153; no. 2; pp. 380 - 388 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Hoboken, USA
John Wiley & Sons, Inc
15-07-2023
Wiley Subscription Services, Inc |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Immunotherapies using checkpoint blockade and BRAF/MEK therapies have improved overall survival (OS) in patients with unresectable melanoma metastases. In this retrospective study, we aimed to demonstrate the resulting increase in melanoma‐specific survival (MSS) and OS after the excision of primary melanomas (≥1 mm thick) and sentinel lymph node (SN) biopsy (SNB). Using Kaplan‐Meier estimates and Cox models, we compared two consecutive cohorts. Patients in cohort 1 (N = 518) underwent SNB between 1998 and 2009, and patients in cohort 2 (N = 460) between 2010 and 2017, when checkpoint blockade and BRAF/(MEK) inhibition became available for the treatment of unresectable relapses. The median follow‐up times were 120 and 73 months, respectively. While recurrence‐free and distant metastasis‐free survival rates remained very similar, MSS and OS increased in favor of cohort 2. The estimated 5‐year OS rate of SN‐positive patients increased by 14.3% (78.5% vs 64.2%, logrank test: P = .005). The MSS benefit was significant even with low SN tumor burden (metastasis diameter < 1 mm). On multivariate analyses, the risk‐reduction in favor of cohort 2 was significant in the total population and in the SN‐negative and SN‐positive subgroups. In SN‐positive patients, besides the availability of modern therapies, SN metastasis diameter and ulceration were independent factors of MSS and OS. Treatment of unresectable melanoma recurrences with modern drug therapies results in significantly higher survival rates in a population with SNB. The survival benefit measured from primary melanoma affects both the SN‐positive and SN‐negative subpopulations.
What's new?
With the introduction of modern targeted therapies and immunotherapies to treat unresectable recurrences in 2010, the OS calculated from excision of the primary melanoma improved significantly in a population with SNB. In multivariate analysis adjusting for Breslow thickness, ulceration and SN status, the relative risk of death nearly halved after the introduction of modern recurrence therapies. Significantly higher OS rates were observed in both SN‐negative and SN‐positive subpopulations. On multivariate analysis of SN‐positive patients, the availability of effective recurrence therapies, SN tumor burden and ulceration were significant for OS. Our study exemplifies that the assumption of proportionality of DMFS and OS can become invalid when effective therapies are used in the later course of the disease. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0020-7136 1097-0215 |
| DOI: | 10.1002/ijc.34475 |