First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma

Wang, Xuechen; Haaland, Benjamin; Hu‐Lieskovan, Siwen; Colman, Howard; Holmen, Sheri L.

doi:10.1002/cnr2.1419

Cited by 8 publications

(8 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A retrospective study by Wang et al assessed BMFS in a cohort of BRAF mut , but not BRAF wt patients, receiving ICI or BRAF+MEK TT. 21 This work showed a prolonged BMFS for patients who received ICI as 1L-therapy compared with patients who received BRAF+MEK. These findings were based on propensity scored matching of single variables and not on a multivariate Cox regression analysis including all important prognostic variables as in our analysis.…”

Section: Discussionmentioning

confidence: 74%

“…19 A French group analyzed 293 melanoma patients without brain metastases who were treated with either anti-PD-1 or anti-PD-L1 antibodies or other systemic therapies (including BRAF inhibitors and chemotherapy) and found a lower incidence of MBM in the PD-1 group compared with patients treated with other therapies. 20 The results of this study are weakened by the fact, that BRAFmut patients were not assessed separately in the multivariate analysis 21 This work showed a prolonged BMFS for patients who received ICI as 1L-therapy compared with patients who received BRAF+MEK. These findings were based on propensity scored matching of single variables and not on a multivariate Cox regression analysis including all important prognostic variables as in our analysis.…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Franklin

Mohr

Bluhm

et al. 2023

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundDespite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.MethodsPatients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).ResultsOf 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwtpatients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmutpatients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmutpatients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmutpatients. In BRAFwtpatients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwtpatients. For BRAFmutpatients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.ConclusionsIn BRAFmutpatients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwtpatients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 78%

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Franklin

Mohr

Bluhm

et al. 2023

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…In a retrospective cohort of 683 BRAF V600 mutated patients, treated over an 8-year period (2011-2019), it was found that the incidence of brain metastasis was approximately double with initial targeted therapy versus immunotherapy (31 versus 16%) and median brain metastases-free survival was 11 months with targeted therapy compared with 42 months with immunotherapy. Therefore, this study suggests that immunotherapy is more effective than targeted therapy in preventing or delaying the occurrence of brain metastases from melanoma, in both adjuvant and metastatic contexts 69 .…”

Section: Discussionmentioning

confidence: 89%

Immunotherapeutic Strategies for Intra-cranial Metastatic Melanoma - a Meta-analysis and Systematic Review

Tang,

Rao,

Peters

et al. 2024

J. Cancer

View full text Add to dashboard Cite

Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable remissions, and long-term overall survival may be achieved in between 50-60% of patients. Although intracranial metastases are very common in melanoma (about 50-75% of all patients with advanced disease), most of the pivotal prospective clinical trials exclude patients with intra-cranial metastases, certainly if their lesions are symptomatic and steroid-requiring and the degree of sensitivity of intra-cranial melanoma to immunotherapy remains uncertain, and requires further investigation especially in view of the demonstrable activity of RAF-MEK inhibitors in this clinical setting and the emergence of stereotactic radiotherapy. Our study aimed to evaluate the efficacy and toxicity of immunotherapy against advanced melanoma patients with brain metastases. In terms of comparative studies, only retrospective analyses could be identified. Based on 3 retrospective studies, treatment of patients with melanoma brain metastases with immunotherapeutic approaches improves overall survival substantially compared with supportive measures alone (no active anticancer treatment). The efficacy of targeted therapy appeared to be comparable to that of immune therapy in terms of overall survival, based on a small number of patients. The combination of concurrent radiation therapy to the brain and systemic immunotherapy led to improved overall survival compared to radiotherapy alone, suggesting potential synergism between the approaches, and combination treatment could be delivered safely. Our review supports the use of immunotherapeutic strategies for these patients although treatment efficacy appears to be lower for symptomatic lesions. In view of the extremely high efficacy of stereotactic radiotherapy approaches in the brain, understanding the interaction between radiotherapy and immunotherapy is vital and should be an area of active investigation.

show abstract

“…Second-line double immunotherapy might be a preferable option with the hazard of fast and dangerous CNS metastases progression following sudden TT discontinuation, a risk that might be overcome by local treatment of the most threatening lesions. Conversely, the interest of second-line triplet TT/antiPD1 therapy in case of morphological or clinical primary or secondary CNS progression after first-line double immunotherapy remains to be investigated [36].…”

Section: Discussionmentioning

confidence: 99%

Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey

Fabre,

Lamoureux,

Meunier

et al. 2024

Melanoma Research

View full text Add to dashboard Cite

Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy.

show abstract

First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma

Cited by 8 publications

References 43 publications

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Immunotherapeutic Strategies for Intra-cranial Metastatic Melanoma - a Meta-analysis and Systematic Review

Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey

Contact Info

Product

Resources

About