Radiation & Immunotherapy Clinical Evidence

[Xrt4life]

Published online today Lancet Oncology:

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30380-7/fulltext

Progression-free survival with pembrolizumab was significantly longer in patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30–0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1–10·4] vs 2·0 months [1·8–2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36–0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5–20·5] vs 5·3 months [3·0–8·5]).

---

Members don't see this ad.

 

[seper]

"thought-provoking", but obvious limitations are here (small numbers, unbalanced).
My back of the envelope calculations for fragility index here is 2, meaning 2 more dead patients at 10 months in XRT group would make p value insignificant.

 

[nkmiami]

There was a vaccine trial for lung cancer several years ago, that also showed a benefit o in patients who had a history of radiation. It was one of the background rationals for the Pacific trial- adjuvant pdl1 inhibitor in stage III -which was positive. Also, patients on a checkpoint inhibitor, who subsequently fail, and then get chemotherapy (like a taxane or temodar in cases of melanoma) seem anecdotally to have an enhanced response...

 

[PruritisAni]

Pacific Trial asks a different question (and the data still embargoed, yes?), but who cares?! This is great news for XRT in the immuno era! This will cause additional trials to open and probably have mass effect for medical oncologists to send more patients see RO for XRT for those people getting pumped full of liquid gold!

 

[RadOncDoc21]

N=1 here but in my "experience," I treated a patient with 30 Gy in 10 for a large posterior chestwall mass (10cm) for palliation. She went on to get nivolumab. One month later, the tumor was gone. It was interesting to say the least.

 

[Palex80]

Lots of selection bias.

Also, evidence of toxicity: Radiation necrosis with stereotactic radiosurgery combined with CTLA-4 blockade and PD-1 inhibition for treatment of intracranial disease in metast... - PubMed - NCBI. Same caveats.

I would not overestimate those "brain necrosis" data on melanoma.
This may very well be a bias caused by the fact that metastatic melanoma patients nowadays actually live enough to develop a necrosis after SRS. In the past, without immunotherapy, metastatic melanoma patients had a miserable overall survival, generally less than a year and more than half of them were dead due to extracranial disease before coming into the time window, when radiation necrosis could occur in the CNS after SRS.

 

[nkmiami]

Clinically, there is difference between "radiation necrosis" and "radiation effect". A transient -pseudo progression (just like with xrt and mgmt positive gbms) can be seen after stereo in the setting of a checkpoint inhibitor. I am not sure that this is the same as necrosis, and the literature seems to be confusing on this.

I posted links on an earlier thread to series that show the presence of radiation effect following stereotactic actually confers a benefit. Certainly, surviving for a year or more after the treatment is correlated with increased likelihood of radiation necrosis.

 

[medgator]

Clinically, there is difference between "radiation necrosis" and "radiation effect". A transient -pseudo progression (just like with xrt and mgmt positive gbms) can be seen after stereo in the setting of a checkpoint inhibitor. I am not sure that this is the same as necrosis, and the literature seems to be confusing on this.

I posted links on an earlier thread to series that show the presence of radiation effect following stereotactic actually confers a benefit. Certainly, surviving for a year or more after the treatment is correlated with increased likelihood of radiation necrosis.

This is happens with lesions in other areas as well, I've heard of cavitating lung lesions which enlarge but end up being related to pseudoprogression

 

[nkmiami]

Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. - PubMed - NCBI

thought provoking:
"The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). "

 

[nkmiami]

Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. - PubMed - NCBI

thought provoking:
"The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). "

 

[evilbooyaa]

Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases. - PubMed - NCBI

thought provoking:
"The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). "

I suppose if you have a choice, this would lean you towards doing SRS first in a newly diagnosed NSCLC with 50%+ PD-L1 expression with a couple brain mets.

However, the main people that would likely be getting PD-L1 inhibition consistently before SRS would be those that were already metastatic who require SRS for metachronous metastases. I imagine this was not accounted for in the study.

I'd be interested in data looking at only those with newly diagnosed NSCLC, including brain mets that are amenable to SRS. Determine which patients got SRS followed by IT, and which ones got IT followed by SRS. Prospectively, if at all possible, to eliminate confounding of "worse systemic disease gets IT prior to SRS". Easier said than done, I'm sure.

 

[Chartreuse Wombat]

^^^^17 patients, 15 co-authors...now that's thought provoking