PD (L) 1-Inhibitors and Radiation: A Good Combination for Local and Systemic Effects?
Main Article Content
Abstract
Radiation therapy is an important component in treatment of solid tumours, in a locally advanced situation and also in a metastatic situation. Indications for using PD- (L) -1 inhibitors increase especially in the metastatic situation, but also in locally advanced solid tumours. Preclinical data show local and systemically effective synergies between local irradiation and an application of checkpoint inhibitors. In the metastatic situation, a possible abscopal effect is of particular interest. This abscopal effect can be achieved especially in concurrent approaches of PD-(L)-1-inhibitors and stereotactic radiation with higher single doses like 3 x 8 Gy or 4 x 12,5 Gy. In locally advanced tumours a local enhancement of the radiation effect, and also an abscopal effect to eliminate potential micrometastases to is of great interest to achieve healing. In this treatment situation promising results are seen in the application of PD-(L)-1-inhibitors as maintenance after concurrent chemoradiation especially in non-small cell lung cancer, as well as in concurrent applications of conventionally fractionated radiotherapy and PD-(L)-1 inhibitors. These approaches and results are considered from the clinician’s point of view.
Article Details
How to Cite
KLAUTKE, Gunther; PIETSCHMANN, Klaus; SROUR, Zohier.
PD (L) 1-Inhibitors and Radiation: A Good Combination for Local and Systemic Effects?.
Medical Research Archives, [S.l.], v. 9, n. 6, june 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2444>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v9i6.2444.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Rückert M, Deloch L, Frey B, Schlücker E, Fietkau R, Gaipl US. Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and Tumor Microenvironment. Cancers 2021; 13, 714
3. Liu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors Journal of Hematology and Oncology 2018; 1:104 Candeias S M, Gaipl US. The Immune System in Cancer Prevention, Development and Therapy. Anticancer Agents Med Chem. 2016; 16:101-7
4. Deng L, Liang H, Burnette B, Beckett M, Darga Th, Weichselbaum RR, Fu Y. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice J Clin Invest 2014; 124: 687-695
5. Frey B, Rückert M, Weber J, Mayr X, Derer A, Lotter M, Bert Ch, Rödel F, Fietkau R, Gaipl US. Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors. Front Immunol. 2017; 8:231
6. Grapin M, Richard C, Limagne E, et al. Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: promising new combination. J Immunother Cancer. 2019; 7:160
7. Jing Y, Zhang Y, Wang J, et al. Association Between Sex and Immune-Related Adverse Events During Immune Checkpoint Inhibitor Therapy. J Natl Cancer Inst. 2021 Mar 10; djab035. online ahead of print.
8. Barhli A, Joulia M L, Tournigand C, Kempf E. Adverse events reporting in phase 3 oncology clinical trials of checkpoint inhibiors: A systemic review. Critical Reviews in Oncology / Hematology 2021; 157
9. Antionia S J, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer N Engl J Med 2017 377:1919-29
10. Peters S, Felip E, Dafni U, et al. Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in Stage III non-small cell lung cancer The ETOP NICOLAS trial. Lung Cancer 2019; 133: 83-87
11. Cousin F, Desir C, Mustapha SB, Mievis C, Coucke Ph, Hustinx R. Incidence, risk factors, and CT characteristics of radiation recall pneumonitis induced by immune checkpoint inhibitor in lung cancer. Radiother Oncol. 2021; 157:47-55.
12. Marcq G, Souhami L, Cury F L, et al. Phase I Trial of Atezolizumab plus Trimodal Therapy in Patients with localized Muscle-Invasive Bladder Cancer. Int J Radiat Oncol Biol Phys. 2021 Jan 6; S0360-3016(20)34729-5 online ahead of print.
13. Chen L, Douglass J, Kleinberg L, et al. Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Int J Radiation Oncol Biol Phys 2018; 100: 916-925. Enright TL, Witt JS, Burr AR, Yadav P, Leal T, Baschnagel AM. Combined Immunotherapy and Stereotactic Radiotherapy Improves Neurologic Outcomes in Patients with Non-small-cell Lung Cancer Brain Metastases. Clinical Lung Cancer 2020; online ahead of print
14. Theelen W S, Peulen H, Lalezari F, et al. Randomized phase II study of pembrolizumab after stereotactic body radiotherapy (SBRT) versus pembrolizumab alone in patients with advanced non-small cell lung cancer: The BEMBRO-RT study. J Clin Oncol 2018; 36 (suppl: abstr 9023)
15. McBride S M, Sherman E, Tsai C, et al. A phase II randomized trial of nivolumab with stereotactic body radiotherapy (SBRT) versus nivolumab alone in metastatic (M1) head and neck squamous cell carcinoma (HNSCC). J Clin Oncol 2018; 36 (suppl: abstr 6009)
16. Mohamad O, Diaz de Leon A, Schroeder S, et al. Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy ONCOIMMUNOLOGY 2018; 7, e1440168 (10 pages)
17. Xu H, Xu X, Ge W, Lei J, Cao D. The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis. Ther Adv Med Oncol. 2020 Dec 18; eCollection 2020
18. Klemen N D, Wang M, Feingold P L, et al. Patterns of Failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma Journal for ImmunoTherapy of Cancer 2019; 7:196
19. Theelen WSME, Peulen HMU, Lalezari F, et al. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial JAMA Oncol. 2019; 5:1276-1282
20. Welsh J, Chen D, Baas P, et al. Radiotherapy to augment pembrolizumab responses and outcomes in metastatic non-small cell lung cancer: Pooled analysis of two randomized trials. J Clin Oncol 2020; 38 (suppl: abstr 9548)
21. Welsh J, Menon H, Chen D, et al. Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial J Immunother Cancer 2020; 8:e001001.
22. Sundahl N, Vandekerkhove G, Decaestecker K, et al. Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. European Urology 2019; 75: 707-711
23. Schubert P, Rutzner S, Eckstein M, et al. Prospective Evaluation of All-lesion Verus Single-lesion Radiotherapy in Combination With PD-1/PD-L1 Immune Checkpoint Inhibitors. Frontiers in Oncology 2020,10; Article 576643
24. Antonia S J, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLCN Engl J Med. 2018;379:2342-2350
25. Faivre-Finn C, Vicente D, Kurata T, et al.
26. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC – an Update From the PACIFIC Trial J Thorac Oncol. 2021 Jan 19; S1556-0864(21)00022-8. doi: 10.1016 online ahead of print.
27. Taugner J, Käsmann L, Eze C, et al. Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients Invest New Drugs. 2021 Mar 11. doi: 10.1007/s10637-021-01091-9. Online ahead of print.
28. Hecht M, Gostian A O, Eckstein M, et al. Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8 J Immunother Cancer. 2020; 82:e001378.
29. Weiss J, Sheth S, Deal A M, et al. Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication Clin Cancer Res. 2020; 26:4260-4267.