Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events.
Immune checkpoint inhibitors
Immune-related adverse events
Overall response rate
Radiotherapy
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
08
08
2022
accepted:
03
07
2023
medline:
11
9
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT -/AE + group, 26.7% in the RT -/AE - group and 18.3% in the RT + /AE - group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT -/AE - and RT + /AE - groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT -/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582-0.935; p = 0.012, and HR 0.620; 95% CI 0.499-0.769; p < 0.001, respectively). Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.
Sections du résumé
BACKGROUND
BACKGROUND
Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear.
METHODS
METHODS
In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed.
RESULTS
RESULTS
Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT -/AE + group, 26.7% in the RT -/AE - group and 18.3% in the RT + /AE - group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT -/AE - and RT + /AE - groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT -/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582-0.935; p = 0.012, and HR 0.620; 95% CI 0.499-0.769; p < 0.001, respectively).
CONCLUSIONS
CONCLUSIONS
Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.
Identifiants
pubmed: 37486396
doi: 10.1007/s00262-023-03494-4
pii: 10.1007/s00262-023-03494-4
pmc: PMC10491510
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3337-3347Informations de copyright
© 2023. The Author(s).
Références
Wei SC, Duffy CR, Allison JP (2018) Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov 8:1069–1086. https://doi.org/10.1158/2159-8290.CD-18-0367
doi: 10.1158/2159-8290.CD-18-0367
pubmed: 30115704
Topalian SL, Hodi FS, Brahmer JR et al (2019) Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with Nivolumab. JAMA Oncol 5:1411–1420. https://doi.org/10.1001/jamaoncol.2019.2187
doi: 10.1001/jamaoncol.2019.2187
pubmed: 31343665
pmcid: 6659167
Sznol M, Ferrucci PF, Hogg D et al (2017) Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. J Clin Oncol 35:3815–3822. https://doi.org/10.1200/JCO.2016.72.1167
doi: 10.1200/JCO.2016.72.1167
pubmed: 28915085
Eigentler TK, Hassel JC, Berking C et al (2016) Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev 45:7–18. https://doi.org/10.1016/j.ctrv.2016.02.003
doi: 10.1016/j.ctrv.2016.02.003
pubmed: 26922661
Antonia SJ, Villegas A, Daniel D et al (2017) Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med 377:1919–1929. https://doi.org/10.1056/NEJMoa1709937
doi: 10.1056/NEJMoa1709937
pubmed: 28885881
Faivre-Finn C, Vicente D, Kurata T et al (2021) Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC—an update from the PACIFIC trial. J Thorac Oncol 16:860–867. https://doi.org/10.1016/j.jtho.2020.12.015
doi: 10.1016/j.jtho.2020.12.015
pubmed: 33476803
Lee NY, Ferris RL, Psyrri A et al (2021) Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol 22:450–462. https://doi.org/10.1016/S1470-2045(20)30737-3
doi: 10.1016/S1470-2045(20)30737-3
pubmed: 33794205
Shah MA, Bennouna J, Doi T et al (2021) KEYNOTE-975 study design: a phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol 17:1143–1153. https://doi.org/10.2217/fon-2020-0969
doi: 10.2217/fon-2020-0969
pubmed: 33533655
pmcid: 7927908
Theelen WSME, Chen D, Verma V et al (2021) Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med 9:467–475. https://doi.org/10.1016/S2213-2600(20)30391-X
doi: 10.1016/S2213-2600(20)30391-X
pubmed: 33096027
Phillips WJ, Baghai T, Ong M et al (2021) A contemporary report of clinical outcomes in patients with melanoma brain metastases. Curr Oncol 28:428–439. https://doi.org/10.3390/curroncol28010045
doi: 10.3390/curroncol28010045
pubmed: 33450821
pmcid: 7903273
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026
doi: 10.1016/j.ejca.2008.10.026
pubmed: 19097774
Hussaini S, Chehade R, Boldt RG et al (2021) Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors – a systematic review and meta-analysis. Cancer Treat Rev. https://doi.org/10.1016/j.ctrv.2020.102134
doi: 10.1016/j.ctrv.2020.102134
pubmed: 33302134
Lee Y, Auh SL, Wang Y et al (2009) Therapeutic effects of ablative radiation on local tumor require CD8 + T cells: changing strategies for cancer treatment. Blood 114:589–595. https://doi.org/10.1182/blood-2009-02-206870
doi: 10.1182/blood-2009-02-206870
pubmed: 19349616
pmcid: 2713472
Gupta A, Probst HC, Vuong V et al (2012) Radiotherapy promotes tumor-specific effector CD8+T cells via dendritic cell activation. J Immunol 189:558–566. https://doi.org/10.4049/jimmunol.1200563
doi: 10.4049/jimmunol.1200563
pubmed: 22685313
Reits EA, Hodge JW, Herberts CA et al (2006) Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 203:1259–1271. https://doi.org/10.1084/jem.20052494
doi: 10.1084/jem.20052494
pubmed: 16636135
pmcid: 3212727
Hiniker SM, Reddy SA, Maecker HT et al (2016) A prospective clinical trial combining radiation therapy with systemic immunotherapy in metastatic melanoma. Int J Radiat Oncol Biol Phys 96:578–588. https://doi.org/10.1016/j.ijrobp.2016.07.005
doi: 10.1016/j.ijrobp.2016.07.005
pubmed: 27681753
pmcid: 5077166
Tang C, Welsh JW, de Groot P et al (2017) Ipilimumab with stereotactic ablative radiation therapy: Phase i results and immunologic correlates from peripheral T cells. Clin Cancer Res 23:1388–1396. https://doi.org/10.1158/1078-0432.CCR-16-1432
doi: 10.1158/1078-0432.CCR-16-1432
pubmed: 27649551
Twyman-Saint Victor C, Rech AJ, Maity A et al (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377. https://doi.org/10.1038/nature14292
doi: 10.1038/nature14292
pubmed: 25754329
Shaverdian N, Lisberg AE, Bornazyan K et al (2017) Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 18:895–903. https://doi.org/10.1016/S1470-2045(17)30380-7
doi: 10.1016/S1470-2045(17)30380-7
pubmed: 28551359
pmcid: 5538772
Spigel DR, Faivre-Finn C, Gray JE et al (2022) Five-year survival outcomes from the pacific trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol 40:1301–1311. https://doi.org/10.1200/JCO.21.01308
doi: 10.1200/JCO.21.01308
pubmed: 35108059
pmcid: 9015199