Pd42-02 optimizing Sequence of Therapy and Radiation Delivery When Combined With Pd-L1 Immune-Checkpoint Inhibition in Bladder Cancer

Tholomier, Côme; Marcq, Gautier; Shinde-Jadhav, Surashri; Ayoub, Mina; Huang, Jia; Kool, Ronald; Skowronski, Rodrigo; Mansure, José João; Kassouf, Wassim

doi:10.1097/ju.0000000000000922.02

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“…day post RT, highlighting the nuances in optimally combining RT with different immunotherapy regimen[44]. While some pre-clinical data show an increase PD-L1 expression and improved survival when RT was given concurrently with ICIs[41,44], we were unable to show any difference in tumor growth rate inhibition when ICI was given either neoadjuvantly, concomitantly or adjuvantly with TMT (Tholomier et al[45], in press). In contrast, in Sundahl et al phase I trial of metastatic MIBC, ORR was 44.4% in the concomitant Pembrolizumab-SBRT vs. 0% in the sequential arm[29].…”

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confidence: 61%

“…Thus, caution should be taken when ICIs are given concurrently with hypofractionated RT. Since the sequencing of TMT and immunotherapy does not appear to affect efficacy in MIBC [45], and in light of acute toxicity concerns presented herein, currently we favor neoadjuvant or adjuvant immunotherapy.…”

Section: Toxicitiesmentioning

confidence: 99%

“…In a mouse model of breast and colon cancer, while all fractionations were effective at controlling the primary irradiated tumor, only the multi-fractionated regimens (8 Gyx3 fractions or 6 Gyx5 fractions), but not the single dose regimen (20 Gy/1 fraction), synergized with anti-CTLA4 to decrease distant tumor growth [48]. Specifically in bladder cancer mouse models, ICIs were more effective when combined with a 10 Gyx2 [27] or 6.25 Gyx2 [45] RT regimens than with a 10 Gyx1 regimen. In the clinical setting, establishing the ideal RT dose and fractionation when combined with immunotherapy remains a challenge requiring further evaluation.…”

Section: Doses and Fractionationmentioning

confidence: 99%

“…While some pre-clinical data show an increase PD-L1 expression and improved survival when RT was given concurrently with ICIs [ 41 , 44 ], we were unable to show any difference in tumor growth rate inhibition when ICI was given either neoadjuvantly, concomitantly or adjuvantly with TMT (Tholomier et al . [ 45 ], in press). In contrast, in Sundahl et al .…”

Section: Practical Considerations Of Combining Rt With Icis In Mibcmentioning

confidence: 99%

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Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response

et al. 2020

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Purpose Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer. Methods Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister. eu/ retrieved ongoing clinical trials on the topic as well. Results Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes. Conclusion RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.

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