Sunday, May 17, 2020

The ipi/nivo combo WITH radiation to melanoma brain mets leads to improved overall survival!!!!


I feel like I have been yelling about this for TEN YEARS - because I have!  Immunotherapy COMBINED with radiation leads to better results for melanoma patients than does either therapy alone!!!  Here is a testament to my yelling: Radiation AND immunotherapy does a body good!

Now, this: 

Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients.  Amaral, Kiecker, Schaefer, et al. J Immunother Cancer. 2020 Mar 8. 

Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.

Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS.

Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab. In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS. Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy, regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population.

Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM.

Again, if you have a melanoma brain met (though we have learned in many other reports that these facts are true for the rest of the body as well) the ipi/nivo combo WITH radiation provides the best overall survival in both symptomatic and asymptomatic patients.  I still get reports from patients for whom this combination has not been provided.  From institutions that should definitely know better.  Sighs, eye rolls, and screaming continues.  But here you go ~ again.  For what it's worth.  - c

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