Preclinical data suggest that combining radiotherapy and immunotherapy will improve the abscopal effect.


Continue Reading

“Preliminary data are promising, but still inconclusive,” Dr Scorsetti told Cancer Therapy Advisor. To date, in-human studies testing the combination of radiotherapy and immunotherapy included small, retrospective, or single institution series, each of which yielded inconsistent results. Several studies reported abscopal responses in patients with melanoma who received radiotherapy or SRS after ipilimumab.8,9,10

Two small studies, 1 retrospective and the other a case series, demonstrated that patients with melanoma brain metastases treated with SRS and ipilimumab had prolonged overall survival, in contrast with those who did not receive ipilimumab.11,12 Two other small studies, however, found no difference in overall survival or local control among patients who received the combination of SRS and ipilimumab and those who received SRS alone.13,14

The timing of SRS and ipilimumab may be important. A small study found that treatment with SRS before or during ipilimumab therapy improved overall survival and regional recurrence, in contrast with SRS administered after ipilimumab.15

According to Dr Scorsetti, “the combination of CTLA-4 blockade or PD-1/PD-L1 blockade plus radiotherapy still needs prospective trials. There are a lot of ongoing trials that will hopefully answer our questions.”

In the studies to-date, the combination is well tolerated. There was, however, an increased risk of radiation necrosis in some studies. “According to the available data, I do not see any significant problems in terms of side effects or toxicity. There are some contradictory results about radiation necrosis in the brain, but it is also true that radionecrosis can be regarded as a marker of good response and better prognosis,” Dr Scorsetti said.

Disclosures: the author has no relevant relationships to report.

References

  1. Franceschini D, Franzese C, Navarria P, et al. Radiotherapy and immunotherapy: can this combination change the prognosis of patients with melanoma brain metastasis? Cancer Treat Rev. 2016;50:1-8. doi: 10.1016/j.ctrv.2016.08.003
  2. Engelhardt B. The blood-central nervous system barriers actively control immune cell entry into the central nervous system. Curr Pharm Des. 2008;14:1555-65.
  3. Prins RM, Vo DD, Khan-Farooqi H, et al. NK and CD4 cells collaborate to protect against melanoma tumor formation in the brain. J Immunol. 2006;177:8448-55.
  4. Heller KN, Pavlick AC, Hodi FS, et al. Safety and survival analysis of ipilimumab therapy in patients with stable asymptomatic brain metastases. J Clin Oncol 29:2011 (suppl; abstr 8581)
  5. Queirolo P, Spagnolo F, Ascierto PA, et al. Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases. J Neurooncol. 2014;118:109–16.
  6. Di Giacomo AM, Ascierto PA, Pilla L, et al. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol. 2012;13:879-86.
  7. Weber JS, Amin A, Minor D, Siegel J, Berman D, O’Day SJ. Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. Melanoma Res. 2011;21:530-4. doi: 10.1097/CMR.0b013e32834d3d88
  8. Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925-31. doi: 10.1056/NEJMoa1112824
  9. Muller-Brenne T, Rudolph B, Schmidberger H, et al. Successful therapy of a cerebral metastasized malign melanoma by whole-brain-radiation and therapy with ipilimumab. J Dtsch Dermatol Ges. 2011;9:787-8.
  10. Bot I, Blank CU, Brandsma D. Clinical and radiological response of leptomeningeal melanoma after whole brain radiotherapy and ipilimumab. J Neurol. 2012;259:1976-8. doi: 10.1007/s00415-012-6488-4
  11. Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117:227-33. doi: 10.3171/2012.5.JNS111929
  12. Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med. 2013;2:899-906. doi: 10.1002/cam4.140
  13. Schoenfeld JD, Mahadevan A, Floyd SR, Dyer MA, Catalano PJ, Alexander BM, et al. Ipilimumab and cranial radiation in metastatic melanoma patients: a case series and review. J Immunother Cancer. 2015;15:50. doi: 10.1186/s40425-015-0095-8