Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial

Kwan, Edmond M.; Spain, Lavinia; Antón, A.; Gan, Chun Loo; Garrett, Linda; Chang, D.W.; Liow, Elizabeth; Bennett, Caitlin; Zheng, Tiantian; Yu, Jianjun; Dai, Chao; Du, Pan; Jia, Shidong; Fettke, Heidi; Abou-Seif, Claire; Kothari, Gargi; Shaw, Margaret; Parente, Phillip; Pezaro, Carmel; Tran, Ben; Siva, Shankar; Azad, Arun

doi:10.1016/j.eururo.2021.08.011

Cited by 41 publications

(36 citation statements)

References 37 publications

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“…Ongoing prospective trials, such as the single-arm phase II TRAP trial ( 20 ) and the Medcare trial ( 21 ), are investigating the role of SABR for oligometastatic CRPC. Since immune-checkpoint inhibitor monotherapy has shown only modest benefits in the mCRPC setting, the ICE-PAC trial aimed at improving outcomes by combining the PD-L1 checkpoint inhibitor avelumab with SABR in patients with both low- as well as high-volume mCRPC after prior androgen-receptor pathway inhibitor therapy ( 22 ). A median radiographic PFS of 8.4 months was observed in this heavily pretreated patient group, of which the majority had >10 metastases.…”

Section: Discussionmentioning

confidence: 99%

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer

et al. 2022

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IntroductionThe addition of stereotactic ablative radiotherapy (SABR) to standard of care for patients with oligometastatic prostate cancer has the potential of improving survival and delaying further metastases. The primary aim of this analysis is to report survival outcomes and pattern of recurrence of patients with hormone-sensitive (HSPC) and castrate-resistant (CRPC) oligometastatic prostate cancer treated with SABR.MethodsThis is a single-center retrospective study of patients with oligometastatic prostate cancer treated in Iridium Network between 2014 and 2018. All patients with oligometastatic (≤3 active lesions) HSPC and CRPC treated with SABR were included. Data were collected using electronic records. Patterns of first progression following SABR were reported. Kaplan-Meier methods were used to determine survival outcomes.ResultsEighty-seven men received SABR to 115 metastases. Nineteen patients were castrate-resistant and 68 hormone-sensitive at the time of SABR. Median follow-up was 41.6 months. In 25% of patients, no decline from baseline PSA was recorded. Median bPFS was 11.7 months (95% CI 7.6 - 18.3) for HSPC as well as CRPC (95% CI 6.4 - 24.0) (p=0.27). Median DMFS was 21.8 (95% CI 16.9 - 43.2) versus 17.6 months (95% CI 6.7 - 26.2) for HSPC versus CRPC, respectively (p=0.018). Median OS was 72.6 months (95% CI 72.6 – not reached) for HSPC and not reached for CRPC (95% CI 35.4 months – not reached) (p=0.026). For the subgroup of oligorecurrent HSPC, short-term androgen-deprivation therapy was associated with improved bPFS (median 6.0 vs. 18.3 months, HR 0.31, p<0.001) and DMFS (median 15.8 vs 29.6 months, HR 0.5, p=0.06). Information on pattern of relapse was retrieved for 79 patients: 45% (36/79) of these patients were long-term disease-free (>18 months), 28% (22/79) of patients wmere oligoprogressive (≤3 new lesions) and 27% (21/79) developed a polymetastatic relapse.ConclusionIn this cohort, oligometastatic HSPC showed potential benefit from SABR with a median DMFS of 21.8 months. Well-selected patients with oligometastatic CRPC may also benefit from SABR. For patients with metachronous and repeat oligorecurrent HSPC, combining SABR with short-term androgen-deprivation therapy was associated with improved bPFS and DMFS. Overall, 36/87 (41%) of patients were still free from clinical relapse at 18 months.

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Section: Discussionmentioning

confidence: 99%

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer

et al. 2022

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“…However, there is still a lack of appropriate strategies for patients with mCRPC who have experienced ADT failure and second-line endocrine therapy. A recent study revealed that avelumab with SABR showed promising activity and acceptable toxicity in treatment-refractory mCRPC ( 26 ), indicating that immunotherapy combined with RT was still the best area of research. However, the data were limited to only one combination of tislelizumab and RT, limiting the treatment potential of mCRPC.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is a scarcity of sufficient studies examining the therapeutic effects of combined anti-PD-1 and multisite SBRT in mCRPC treatment, necessitating further research. Another phase II trial demonstrated that avelumab combined with SBRT exhibited elevated activity and acceptable toxicity in treatment-refractory mCRPC ( 26 ). Although a study reported that SBRT with a few fractionations was the best choice for the abscopal effect ( 27 ), an appropriate RT technique should be chosen based on the symptoms and condition of the patient with mCRPC.…”

Section: Introductionmentioning

confidence: 99%

Multisite Radiotherapy Combined With Tislelizumab for Metastatic Castration-Resistant Prostate Cancer With Second-Line and Above Therapy Failure: Study Protocol for an Open-Label, Single-Arm, Phase Ib/II Study

et al. 2022

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BackgroundTislelizumab combined with radiotherapy as a salvage treatment for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC) is not reported. This study aimed to describe a protocol to evaluate the safety and efficacy of multisite radiotherapy combined with tislelizumab as a salvage therapy for mCRPC in patients who had at least one second-line treatment failure.MethodsThe study included patients with mCRPC who had at least one lesion suitable for radiotherapy and failed androgen deprivation therapy (ADT), followed by at least one novel second-line endocrine therapy. All patients received tislelizumab monotherapy induction therapy for two cycles, then combined with multisite radiotherapy for one cycle, followed by tislelizumab maintenance therapy, until either disease progressed or the patient developed unacceptable toxicity. Radiation methods and lesions were individually selected according to the specified protocol. Primary endpoints included safety and objective response rate. Secondary endpoints included prostate-specific antigen (PSA) response rate, disease control rate, overall survival, radiographic progression-free survival (rPFS), and biochemical progression-free survival (bPFS). Furthermore, the exploratory endpoints included the identification of the predictive biomarkers and exploration of the correlation between biomarkers and the tumor response to the combined regimen.DiscussionThis study included three treatment stages to evaluate the efficacy of immunotherapy and the combination of immunotherapy and radiotherapy for patients with mCRPC who have had at least second-line treatment failure. Additionally, radiation-related and immune-related early and late toxicities were determined, respectively. Furthermore, the study also aimed to identify the predictive biomarkers associated with immunotherapy for treating mCRPC.Trial Registrationhttps://www.chictr.org.cn/showproj.aspx?proj=126359, identifier ChiCTR2100046212.

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“…This trial also analyzed cf RNA as a biomarker and used it to measure pathogenicity. The results of this trial indicated that cf RNA has the potential to be used to measure the tumor response and the development/emergence of resistance [ 124 ].…”

Section: Clinical Trialsmentioning

confidence: 99%

Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management

et al. 2022

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Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management.

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Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial

Cited by 41 publications

References 37 publications

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer

Multisite Radiotherapy Combined With Tislelizumab for Metastatic Castration-Resistant Prostate Cancer With Second-Line and Above Therapy Failure: Study Protocol for an Open-Label, Single-Arm, Phase Ib/II Study

Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management

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