Neoadjuvant, SBRT With Intratumoural Pembrolizumab Followed by Neoadjuvant Chemotherapy in Breast Cancer

Summary

This study will evaluate the immune-priming effects of stereotactic body radiation therapy (SBRT) regimen coupled with two injections of pembrolizumab in high-risk primary breast carcinoma prior to neoadjuvant chemotherapy. Preliminary results from the investigators' local TRIO Trial suggest that SBRT prior to neoadjuvant chemotherapy (NAC) may result in improved response rates due to the combined effect of radiation therapy (RT) and chemotherapy. The investigators aim to augment this effect with the addition of pembrolizumab, a monoclonal antibody that binds to and blocks programmed cell death protein 1 (PD-1).

Timeline

Start

2026-01-19

Primary completion

2027-07

Completion

2029-02

Publications

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• Background Greco C, Zelefsky MJ, Lovelock M, Fuks Z, Hunt M, Rosenzweig K, Zatcky J, Kim B, Yamada Y. Predictors of local control after single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1151-7. doi: 10.1016/j.ijrobp.2009.12.038. Epub 2010 May 25.
• Background Hong WX, Haebe S, Lee AS, Westphalen CB, Norton JA, Jiang W, Levy R. Intratumoral Immunotherapy for Early-stage Solid Tumors. Clin Cancer Res. 2020 Jul 1;26(13):3091-3099. doi: 10.1158/1078-0432.CCR-19-3642. Epub 2020 Feb 18.
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• Background Iaccarino G, Pinnaro P, Landoni V, Marzi S, Soriani A, Giordano C, Arcangeli S, Benassi M, Arcangeli G. Single fraction partial breast irradiation in prone position. J Exp Clin Cancer Res. 2007 Dec;26(4):543-52.
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• Background Kimple RJ, Klauber-DeMore N, Kuzmiak CM, Pavic D, Lian J, Livasy CA, Chiu WM, Moore DT, Sartor CI, Ollila DW. Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer. Ann Surg Oncol. 2011 Apr;18(4):939-45. doi: 10.1245/s10434-010-1392-6.
• Background Lemanski C, Azria D, Gourgon-Bourgade S, Gutowski M, Rouanet P, Saint-Aubert B, Ailleres N, Fenoglietto P, Dubois JB. Intraoperative radiotherapy in early-stage breast cancer: results of the montpellier phase II trial. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):698-703. doi: 10.1016/j.ijrobp.2009.02.039. Epub 2009 May 23.
• Background Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, Zhou G, Rajapaksa R, Green MR, Torchia J, Brody J, Luong R, Rosenblum MD, Steinman L, Levitsky HI, Tse V, Levy R. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 2013 Jun;123(6):2447-63. doi: 10.1172/JCI64859.
• Background Melero I, Castanon E, Alvarez M, Champiat S, Marabelle A. Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Nat Rev Clin Oncol. 2021 Sep;18(9):558-576. doi: 10.1038/s41571-021-00507-y. Epub 2021 May 18.
• Background Middleton MR, Hoeller C, Michielin O, Robert C, Caramella C, Ohrling K, Hauschild A. Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives. Br J Cancer. 2020 Sep;123(6):885-897. doi: 10.1038/s41416-020-0994-4. Epub 2020 Jul 27.
• Background Minniti G, Salvati M, Muni R, Lanzetta G, Osti MF, Clarke E, Costa A, Bozzao A, Trasimeni G, Enrici RM. Stereotactic radiosurgery plus whole-brain radiotherapy for treatment of multiple metastases from non-small cell lung cancer. Anticancer Res. 2010 Jul;30(7):3055-61.
• Background Ollila DW, Klauber-DeMore N, Tesche LJ, Kuzmiak CM, Pavic D, Goyal LK, Lian J, Chang S, Livasy CA, Sherron RF, Sartor CI. Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively. Ann Surg Oncol. 2007 Feb;14(2):660-9. doi: 10.1245/s10434-006-9154-1.
• Background Palma D, Visser O, Lagerwaard FJ, Belderbos J, Slotman BJ, Senan S. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol. 2010 Dec 10;28(35):5153-9. doi: 10.1200/JCO.2010.30.0731. Epub 2010 Nov 1.
• Background Palta M, Yoo S, Adamson JD, Prosnitz LR, Horton JK. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):37-42. doi: 10.1016/j.ijrobp.2010.09.041. Epub 2010 Nov 17.
• Background Park C, Papiez L, Zhang S, Story M, Timmerman RD. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):847-52. doi: 10.1016/j.ijrobp.2007.10.059.
• Background Pinnaro P, Arcangeli S, Giordano C, Arcangeli G, Impiombato FA, Pinzi V, Iaccarino G, Soriani A, Landoni V, Strigari L. Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer. Radiat Oncol. 2011 Nov 11;6:155. doi: 10.1186/1748-717X-6-155.
• Background Sacchini V, Beal K, Goldberg J, Montgomery L, Port E, McCormick B. Study of quadrant high-dose intraoperative radiation therapy for early-stage breast cancer. Br J Surg. 2008 Sep;95(9):1105-10. doi: 10.1002/bjs.6208.
• Background Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.
• Background Theberge V, Whelan T, Shaitelman SF, Vicini FA. Altered fractionation: rationale and justification for whole and partial breast hypofractionated radiotherapy. Semin Radiat Oncol. 2011 Jan;21(1):55-65. doi: 10.1016/j.semradonc.2010.08.007.
• Background Vaidya JS, Baum M, Tobias JS, Wenz F, Massarut S, Keshtgar M, Hilaris B, Saunders C, Williams NR, Brew-Graves C, Corica T, Roncadin M, Kraus-Tiefenbacher U, Sutterlin M, Bulsara M, Joseph D. Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1091-7. doi: 10.1016/j.ijrobp.2010.07.1996. Epub 2010 Oct 15.
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• Background Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010 Jul 10;376(9735):91-102. doi: 10.1016/S0140-6736(10)60837-9.
• Background Veronesi U, Orecchia R, Luini A, Galimberti V, Zurrida S, Intra M, Veronesi P, Arnone P, Leonardi MC, Ciocca M, Lazzari R, Caldarella P, Rotmensz N, Sangalli C, Sances D, Maisonneuve P. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat. 2010 Nov;124(1):141-51. doi: 10.1007/s10549-010-1115-5. Epub 2010 Aug 15.
• Background Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Leonardi MC, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(13)70497-2. Epub 2013 Nov 11.
• Background Videtic GM, Stephans KL. The role of stereotactic body radiotherapy in the management of non-small cell lung cancer: an emerging standard for the medically inoperable patient? Curr Oncol Rep. 2010 Jul;12(4):235-41. doi: 10.1007/s11912-010-0108-1.

Drugs

Indications