I know, I know!!! I've said this a million times. Radiation administered ~ CONCOMITANTLY, CURRENTLY, AT THE SAME TIME, IN COMBINATION WITH ~ immunotherapy ~ provides much better outcomes for folks with melanoma brain mets. Here's my last report with a link to a zillion others: March 2018 - CONCURRENT radiation and immunotherapy for brain mets is BEST!!!! (yes, AGAIN!!!)
Now, there's this ~
Impact of simultaneous radiotherapy in melanoma patients treated with pembrolizumab in the French early access program. Saiag, Mortier, Dutriaux, et al. ASCO Meeting, 2018.
Information
on the use of radiotherapy in anti-PD-1 monoclonal antibody-treated
melanoma pts is limited although some data support a synergistic
effect. We
investigated the influence of simultaneous radiotherapy in a
multicenter ambispective cohort of advanced melanoma patients
initiating pembrolizumab between May 2014-Sept 2015. Palliative or
curative intent of radiotherapy was recorded.
663
pts (151 pts with brain metastases) were included in 40 French
centers, with 125 pts (19%) receiving simultaneous radiotherapy (43
pts with greater than/= to1 brain metastasis, 82 without). No
significant difference in baseline LDH level, ECOG performance
status, N of metastatic sites, previous treatment lines or
post-progression therapies was observed between pts who did or did
not receive radiation. As compared to pts without brain metastases,
radiotherapy was performed in brain metastases pts closer to
initiation of pembrolizumab (median 1.1 m vs 3.7 m) and more
frequently with a curative intent (72% vs 37%). Globally, OS was
longer in radiated vs non-radiated pts (median 18.9 m vs 12.5). This
benefit was mainly driven by the pts with brain metastases (OS:
median 26.0 m vs 6.0 m) (PFS: 6.4 m vs 2.5 m). No significant
difference was seen for OS in radiated pts without brain metastasis,
who were mainly radiated later and for palliative reasons and had
shorter PFS (2.8 vs 3.4 m). Simultaneous
radiotherapy may enhance efficacy of anti-PD1 therapy, particularly
when initiated early and in brain metastases pts.
Here, from an initial 663 melanoma patients, 125 patients were given pembro with simultaneous radiation. 43 of these had brain mets while 83 did not. Overall survival was better in radiated patients (18.9 months vs 12.5 months) though this benefit was driven mostly by the brain met folks who demonstrated an OS of (26 months vs 3.7 months). However, "No significant difference was seen for OS in radiated pts without brain metastasis, who were mainly radiated later and for palliative reasons and had shorter PFS (2.8 vs 3.4 m)." So the conclusion was: "Simultaneous radiotherapy may enhance efficacy of anti-PD1 therapy, particularly when initiated early and in brain metastases pts."
Okay, #1, this told us what we already knew: Immunotherapy works best for folks with brain mets when given WITH radiation therapy!!! But, it seems possible (at least to me) that that same rule may apply to folks with melanoma elsewhere. Because...though in this study the folks with radiation given to sites that were NOT brain mets did not see any particular benefit of the pembro/radiation combo...the authors acknowledge that those patients were "radiated later and for palliative reasons". I'm just wondering if it is possible that had THOSE patients been given radiation WITH their pembro - would they have done better, too????
And just when we think we have that all figured out....there's this ~
BRAF
V600 Mutation and BRAF Kinase Inhibitors in Conjunction With
Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A
Multicenter Retrospective Study. Mastorakos,
Xu, Yu, et al. Neurosurgery.
2018 May 29.
The
BRAF mutation has been identified as a potent target for the
treatment of metastatic melanoma and BRAF inhibitors (BRAFi) have
demonstrated promising results against melanoma brain metastases
(BM). In
this multicenter retrospective cohort study, 198 patients with known
BRAF mutation status and treated with stereotactic radiosurgery (SRS)
between 2011 and 2015 were identified. The median survival after the diagnosis of BM in patients with BRAF mutation who received BRAFi was increased compared to survival in patients with wild-type BRAF (BRAF wt). BRAF mutated Patients who received BRAFi following SRS had improved survival compared to patients who received it before or concurrently. PD-1 inhibitors improved survival, with more pronounced effect in patients not carrying the BRAF mutation. Among the patients who were treated with BRAFi, 10.4% developed intracerebral hematoma (ICH), in comparison to 3% of patients who were not treated with BRAFi.
In the setting of widespread use of BRAFi, the presence of a BRAF mutation is an independent predictor of better prognosis in patients with melanoma BM that underwent SRS. The effect of BRAFi is optimal when treatment is initiated at least 1 wk following SRS. BRAFi may increase the frequency of asymptomatic ICH.
So, here, folks with BRAF positive melanoma did better when treated with BRAF inhibitors than did those who were wild type. (Is that really news?) BRAF positive folks also did better when they were given BRAFi AFTER radiation to their brain mets, rather than those who were given BRAFi before or concurrently. Administration of BRAFi one week after radiation was best. However, folks given BRAFi did have an increased chance of developing some bleeding in the brain.
Clear as mud?? Not really, huh? Well, that's melanoma for you. Not sure the BRAFi/radiation report is an absolute yet. So at this point, zap your brain mets, start BRAFi the following week, and make sure your doc observes you closely for ICH. But, we certainly have more than enough info on immunnotherapy and radiation in melanoma brain mets to know for sure: Get yo SH!# TOGETHER!!! Hey, I like that little pneumonic!!! Meaning, get your immunotherapy WITH your radiation treatment!!!
Hang tough ratties!!! Cause melanoma don't play and the whole thing is just cray cray!!! - c
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