Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen‐receptor–targeted therapy for metastatic castration‐resistant prostate cancer

Cancer ◽  
2021 ◽  
Author(s):  
Shabbir M. H. Alibhai ◽  
Henriette Breunis ◽  
Aaron R. Hansen ◽  
Richard Gregg ◽  
Padraig Warde ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Research Group ◽  
Older Men ◽  
Castration Resistant Prostate Cancer ◽  
Aging Research ◽  
Castration Resistant

Metastasis free survival in older men with nonmetastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: An FDA-pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12038-12038
Author(s):  
Harpreet Singh ◽  
Lijun Zhang ◽  
Anup Amatya ◽  
Yutao Gong ◽  
Daniel L. Suzman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Adverse Events ◽  
Older Men ◽  
Pooled Analysis ◽  
Cytotoxic Chemotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Time To Initiation

12038 Background: The FDA has approved three androgen receptor (AR) inhibitors for nonmetastatic castration-resistant prostate cancer (nmCRPC) based on improvements in metastasis-free survival (MFS). MFS is an earlier endpoint, defined as the time from randomization to either imaging-detectable distant disease or death. This pooled analysis examines MFS, time to initiation of cytotoxic chemotherapy (TTCyto), and safety outcomes in men over 80 treated with AR inhibitors. Methods: Data was pooled from three randomized controlled studies (n=4117) of AR inhibitors for nmCRPC. The treatment effect of AR inhibitors on MFS and TTCyto across age groups was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model. Hazard Ratios for MFS and TTCyto were adjusted for baseline ECOG, total Gleason score, PSA doubling time, and prior bone-targeting therapy. Results: For patients age 80 years or older (n=675) who were treated with AR inhibitors, the hazard ratio was 0.38 (95% CI 0.29, 0.49) with an estimated median MFS of 40 months (95% CI 36, 41) versus 22 months (95% CI 18, 29) for those treated with placebo (n=348). For patients <80 (n=2019) treated with AR inhibitors, the HR was 0.31 (95% CI 0.27, 0.36) with an estimated median MFS of 41 months (95% CI 36, NR) versus 16 months (95% CI 15, 18) for those treated with placebo (n=1075). Patients over 80 also derived similar improvements in time to initiation of cytotoxic chemotherapy (HR 0.43 95% CI 0.23, 0.82), compared to their younger counterparts (HR 0.41 95% CI 0.33, 0.50). See Table for selected safety outcomes. Conclusions: In an exploratory subgroup analysis, older men (≥80) with nmCRPC derived similar benefit in MFS and time to initiation of cytotoxic chemotherapy with AR inhibitors compared with younger patients. Men age 80 and above experienced higher rates of Grade 3-4 adverse events, serious adverse events, falls, and fractures. This trend towards increased toxicity was observed regardless of treatment arm. Analysis of patient reported outcomes is ongoing. [Table: see text]

scholarly journals Androgen Receptor Targeted Therapy + Radiotherapy in Metastatic Castration Resistant Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria Massaro ◽  
Giuseppe Facondo ◽  
Gianluca Vullo ◽  
Anna Maria Aschelter ◽  
Alessandro Rossi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Progression Free Survival ◽  
Conformal Radiotherapy ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

ObjectivesTo investigate whether radiotherapy as metastasis-directed therapy (MDT) on oligo-progressive sites in metastatic castration-resistant prostate cancer (mCRPC) patients during treatment with androgen receptor-targeted therapy (ARTT) may lead to control resistant lesions, prolonging ARTT. We analysed progression free survival, overall survival and prognostic parameters that can identify patients that best suit to this approach.Patients and MethodsRetrospective analysis of a total of 67 lesions in 42 mCRPC patients treated with ablative or palliative RT to oligoprogressive lesions during ARTT. Twenty-eight patients (67%) underwent ARTT with Abiraterone acetate and 14 patients (33%) underwent ARTT with Enzalutamide. Median time between the start of ADT and ARTT beginning was 50.14 months (range 3.37-219 months). We treated 58 lesions (87%) with 3D conformal radiotherapy (3DCRT) and nine lesions (13%) with stereotactic body radiotherapy (SBRT). The Kaplan Meier method was used to assess the median overall survival (OS) and the progression-free survival (PFS).ResultsMedian follow-up was 28 months (range 3-82 months). Median OS was 32.5 months (95% CI 25.77-39.16), 1 and 2-year OS were 71.6% and 64.1%, respectively. Median PFS was 19,8 months (95% CI 11.34–28.31), 1 and 2-year PFS were 67.2% and 47.4%, respectively. Median OS for patients that underwent radiotherapy before 6 months from the start of ARTT was 23.4 months (95% CI 2.04-44.89) and 45.5 months (95% CI 31.19-59.8) for patients that underwent radiotherapy after 6 months (p = 0.009).ConclusionLocal ablative radiation therapy directed to progressive metastasis is a non-invasive, well tolerated treatment with efficacy on prolonging clinical benefit of systemic therapies with ARTT. Patients who underwent RT &gt;6 months from the start of ARTT presented a statistically better OS and PFS compared with patients who underwent radiotherapy &lt;6 months from the start of ARTT.

scholarly journals Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)

2021 ◽  
Author(s):  
Fred Saad ◽  
Kim N. Chi ◽  
Neal D. Shore ◽  
Julie N. Graff ◽  
Edwin M. Posadas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Open Label Phase ◽  
Phase 1B

Abstract Purpose To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer. Results Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation. Conclusions These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC. Trial registration no. NCT02924766 (ClinicalTrials.gov).

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