Radium-223 dichloride (Ra-223) in U.S. expanded access program (EAP).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 247-247 ◽  
Author(s):  
Nicholas J. Vogelzang ◽  
Daniel Celestino Fernandez ◽  
Michael J. Morris ◽  
Andrei Iagaru ◽  
Alan Brown ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Median Time ◽  
Radium 223 ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Psa Progression ◽  
Grade 3 ◽  
Efficacy Parameters ◽  
Castrate Resistant ◽  
Ecog Ps

247 Background: The ALSYMPCA study (Parker, NEJM, 2013) was the basis for regulatory approval of Ra-223 for the treatment of castrate-resistant prostate cancer (CRPC) patients (pts) with symptomatic bone metastases. The aim of this prospective EAP was to monitor acute and long-term safety of Ra-223. Pt profiles and findings in the EAP setting are presented. Methods: In the EAP, CRPC pts with symptomatic bone metastases who either received or were not eligible for docetaxel received Ra-223 50 kBq/kg by injection q4wks for 6 cycles. Primary endpts: ECOG PS, symptomatic skeletal-related events (SSE), treatment-emergent adverse events [TEAEs], routine laboratory tests including PSA. Exploratory endpts: overall survival (OS), SSE rates, changes in total ALP (tALP)/PSA responses, time to tALP normalization, and to tALP and PSA progression. Descriptive statistics were used. Results: 184 pts entered treatment; baseline characteristics were similar as seen in ALSYMPCA (N=600) (exceptions in table); 67% had total ALP <220 U/L and 47% mild/moderate pain. 81/184 (44%) received all 6 injections; 26 (14%) had a dose interruption/delay, 18 due to AEs. Median OS was 17m (50/184; 27% pts). TEAEs occurring at ≥10% were anemia, fatigue, diarrhea, and nausea. The most common Grade 3/4 hematologic TEAE was anemia (11%). Majority of pts had no change in ECOG PS within each trt cycle. 19 (10%) pts had an SSE, 13 received EBRT for bone pain. 33% of pts had a ≥30% confirmed ALP decline from baseline and 16% had a ≥50% decline. Median time to ALP progression was not reached. Median time to PSA progression was 4m and 6% had a confirmed PSA response. Conclusions: In heavily pretreated patients with CRPC and bone metastases and in an EAP setting, Ra-223 was well tolerated with no new safety concerns and a positive effect on efficacy parameters. Clinical trial information: NCT01516762. [Table: see text]

PRINT: Prostate cancer intensive, non-cross reactive therapy for CRPC—Early observations of feasibility and efficacy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 310-310
Author(s):  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao ◽  
Matt D. Galsky ◽  
Richard Lorne Bakst ◽  
Robert Stewart ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Primary Endpoint ◽  
Abiraterone Acetate ◽  
Radium 223 ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3 ◽  
Additional Therapy ◽  
Clinical Trial Information

310 Background: Optimal sequencing of approved therapeutic agents in mCRPC is not known. The standard approach, is to treat until resistance then switch. The PRINT trial explores the efficacy of treating mCRPC with a rapidly-cycling, non-cross reactive regimen as a way to more effectively treat an intrinsically heterogeneous disease, to delay or prevent drug resistance, and minimize treatment toxicity. Methods: Patients were treated with 3 consecutive treatment modules, each of 12 weeks' duration: 1. abiraterone acetate 1000 mg PO daily and prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV and carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily and radium-223 50 kBq/kg IV q4 weeks (in those with bone metastases). After completion of this 9 month regimen, patients are followed on ADT alone. Primary endpoint is PSA or radiographic time to disease progression. Results: From 3/2017 to 10/2018, 28 of 40 planned men with mCRPC were enrolled, 19 (67.9%) with bone metastases. PSA response rates ( > 90%/ > 50%), compared to baseline, following each treatment module: 1. 50%/78.6%; 2. 50%/92.7%; 3. 64.39%/92.7%. Currently, 14 patients have completed the study regimen with median follow up of 3.6 months, 8 of whom continue without any additional therapy. Of the patients evaluable for primary endpoint, median time to PSA progression is 96+ days (95% CI 82-110+ days). The regiment was well tolerated, grade 3/4 adverse effects include: hyperglycemia (17.9%), diarrhea (7.1%), anemia (3.6%), fatigue (3.6%), neutropenia (3.6%), thrombocytopenia (3.6%). Measurable response and molecular correlate data will be presented. Conclusions: Treatment of mCRPC with a rapidly-cycling non-cross reactive regimen is feasible, demonstrates significant antitumor benefits, and is well tolerated. Further follow up will determine if PRINT delays progression compared with standard approaches. Clinical trial information: NCT02903160.

Use of radium-223 in heavily pretreated metastatic castrate resistant prostate cancer (mCRPC) patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 275-275
Author(s):  
Dipenkumar Modi ◽  
SeongHo Kim ◽  
Hirva Mansurali Mamdani ◽  
Clara Hwang ◽  
Hersham Gayar ◽  
...  
Keyword(s):  
Visual Assessment ◽  
Prior Therapy ◽  
Pain Scores ◽  
Radium 223 ◽  
Heavily Pretreated ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Pretreated Patients ◽  
Castrate Resistant ◽  
Post Therapy

275 Background: Ra 223 has been shown to improve overall survival in mCRPC patients with symptomatic bone metastases. Little is known about the utility of following PSA during Ra 223 therapy in heavily pretreated patients. Here we report our experience with Ra 223 in such a setting. Methods: We reviewed 26 heavily pretreated mCRPC patients who received Ra 223 at 3 institutions and evaluated the trend of PSA during treatment, the association of various demographic, clinical and biochemical variables with PSA trend, and the correlation of PSA trend with clinical outcomes. Patients received IV Ra 223 every 4 weeks with a planned total of 6 cycles. Results: Twenty six patients were treated between August 2013 and August 2014. Median age was 70 years (range 49-80); 77% (N=20) were European American (EA), 19% (N=5) were African Americans (AA), unknown for 1 patient. Prior therapy included docetaxel in 77% (N=20) of patients, cabazitaxel in 19% (N=5), enzalutamide in 65% (N=17), and abiraterone in 54% (N=14). 62% (N=16) received at least 3 prior therapies.35% (N=9) received all 6 cycles of Ra 223, while 18% (N=4) received only 1 cycle. Median alkaline phosphatase level increased from 126.0 U/L (54.0, 514.0) to 332.0 U/L (136.0, 566.0) at the end of Ra 223 therapy. Median pre-therapy PSA was 100.3 and median post-therapy PSA was 429.5. 54% (N=14) patients had >50% rise in PSA. Higher pre-therapy PSA was strongly associated with higher post-therapy PSA (Pearson’s correlation coefficient = 0.84, p <0.0001). Faster rate of rise in PSA was observed in patients with higher number of bone metastasis and those who have had prior therapy with docetaxel. The patients with >50% PSA rise had reported overall higher pain scores by visual assessment scale. Ra 223 was discontinued in 15% (N=4) patients due to myelosuppression and in 8% (N=2) due to side effects. Conclusions: All heavily pretreated patients receiving Ra 223 therapy for mCRPC showed PSA progression and reasonable tolerability. Only 35% of patients were able to receive all 6 cycles of Ra 223.

CTNI-33. METRONOMIC TEMOZOLOMIDE THERAPY IN HEAVILY PRETREATED PATIENTS WITH RECURRENT GLIOBLASTOMA: A LARGE MONO-INSTITUTIONAL RETROSPECTIVE STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi66-vi67
Author(s):  
Alberto Bosio ◽  
Giulia Cerretti ◽  
Marta Padovan ◽  
Mario Caccese ◽  
Valentina Guarneri ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
First Line Therapy ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Third Line ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Ecog Ps

Abstract BACKGROUND Despite advances in surgical and first-line treatment, all glioblastoma pts relapse. The aim of this study is to evaluate the benefit of metronomic temozolomide (mTMZ) for recurrent glioblastoma. METHODS 120 pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis. RESULTS mFollow-up was 15.6ms, mAge 59ys (range 18-81), ECOG PS 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated in 66 of 105 (62%) evaluable pts, IDH mutated in 9 of 106 (8%). mNumber of prior lines of treatment was 2 (range 1-7); 41% of pts received mTMZ beyond the third line. mTime between last standard TMZ (sTMZ) cycle and mTMZ administration was 6ms (range 1-50); 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS 2.6ms (95% CI 2.3-2.8). On univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p= 0.03); mOS for pts with ECOG PS &gt; or ≤ 2 was 2.3 and 6.0ms (p&lt; 0.001). On multivariate analysis, MGMTmet status (HR= 2.3, 95% CI, p= 0.004) and ECOG PS (HR= 0.5, 95% CI, p= 0.017) remained significant for PFS; ECOG PS (HR= 0.4, 95% CI, p= 0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon. CONCLUSIONS Rechallenge with mTMZ can be a well tolerated treatment option for recurrent glioblastoma, even in heavily pretreated pts. Pts with MGMTmet and good ECOG PS might report the major benefit.

A multicenter phase II study of pemetrexed and cisplatin in patients with advanced gastric cancer (AGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14008-14008
Author(s):  
Y. Bang ◽  
Y. Kim ◽  
H. C. Chung ◽  
W. Kang ◽  
S. Park ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Median Time ◽  
Progressive Disease ◽  
Treatment Schedule ◽  
Curative Surgery ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Common Grade ◽  
Grade 3

14008 Background: Pemetrexed is a novel folate antimetabolite, and it inhibits a number of folate-dependent enzymes. This agent has demonstrated activity in a variety of tumor types including AGC. This study was performed to evaluate the combination of pemetrexed and cisplatin in the treatment of AGC. The primary endpoint was response rate, and secondary endpoints were duration of response, time to progressive disease, time to treatment failure, overall survival, and toxicity. Methods: Patients with stage IV AGC not to be amendable to curative surgery and measurable disease were eligible. Pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 were given on day 1, every 21 days. Treatment was supplemented with folic acid, vitamin B12, and dexamethasone. Response was assessed by RECIST, and toxicity was assessed by NCI-CTC v 2.0. Results: From October 2003 to September 2004, 51 patients were enrolled, but 1 did not meet the eligibility criteria. There were 37 men and 13 women with a median age of 56 years (range, 24–69) and an ECOG PS 0/1 for 14/36 patients; all had metastatic disease. Of 50 evaluable patients, there were no complete responses, and 13 had confirmed partial responses (26%; 95% CI, 14.6%-40.3%). Fifteen patients (30%) had stable disease, and 21 (42%) progressed, and 1 (2%) was unknown. Among 13 responders, the median durarion of response was 3.60 months (95% CI, 2.80–9.40). Median time to progressive disease was 2.8 months (95% CI, 2.20–4.40), and median overall survival was 6.6 months (95% CI, 4.80–10.40). The median time to treatment failure was 2.10 months (95% CI, 1.00–2.80). Survival estimates were 32.0% at 3 months and 7.0% at 6 months. A total of 212 cycles were administered to 51 patients (median 4 [range, 1–13]). Based on 51 patients, most common grade 3/4 hematologic toxicities were neutropenia (49.0%), leukopenia (19.7%), and anemia (13.7%); the most common grade 3/4 nonhematologic toxicities were hyponatremia (15.7%), anorexia (9.8%), nausea (7.8%), and vomiting (7.8%). Conclusions: : The combination of pemetrexed and cisplatin in the current dose and schedule has a modest activity and a mild toxicity profile in patients with AGC. Further study is warranted using a different dose and treatment schedule. [Table: see text]

Phase II multicenter study of abiraterone acetate (AA) plus prednisone therapy in docetaxel-treated castration-resistant prostate cancer (CRPC) patients (pts): Impact of prior ketoconazole (keto)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5048-5048 ◽  
Author(s):  
D. C. Danila ◽  
J. de Bono ◽  
C. J. Ryan ◽  
S. Denmeade ◽  
M. Smith ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pivotal Study ◽  
Heavily Pretreated ◽  
Psa Progression ◽  
Hormonal Therapies ◽  
Ecog Ps ◽  
Anti Tumor Activity

5048 Background: AA is a potent blocker of CYP17, required for synthesis of testosterone in the testes, adrenals, and prostate tissue. Study objectives included confirming AA antitumor activity and safety in multicenter setting, describing changes in ECOG PS, and comparing keto-naïve pts to keto-exposed pts. Methods: The 58 pts had progressive, metastatic CRPC and had failed hormonal therapy and up to two cytotoxic regimens, including docetaxel. AA (1,000 mg QD) and prednisone (5mg BID) were administered daily, the registration trial regimen. 56/58 pts had available data. Results: Baseline demographics: median age - 69.0 (44–86) yrs; median PSA - 151.00 (10.0–3846.0) ng/mL; ECOG 0 (n = 23), 1 (n = 30), 2 (n = 2), missing (n = 1); median prior hormonal therapies were 4 and chemo 1; 24 pts had prior keto, 32 pts were keto-naïve and 2 pts had no data on keto exposure. 45% pts had total maximal PSA decline ≥50%. Total maximal PSA decline (≥30%, ≥50% and ≥90%) in prior keto vs. keto-naïve pts was observed respectively, in: 10 (42%) vs. 20 (63%) pts; 8 (33%) vs. 17 (53%); 1 (4%) vs. 10 (31%). From 32 pts with ECOG 1 or 2, 16 pts (50%, 95% CI 32–68) improved (PS 1 to 0 in 14 pts, PS 2 to 1 in 1 pt; PS 2 to 0 in 1 pt); 39 pts (64% of total 58 pts) maintained PS. Median time to PSA progression was 169 days (95% CI 82–200): keto-naïve-198 days, prior keto-99 days. The majority of AA-related adverse events (AEs) were grade 1–2. No AA-related grade 4 AE was noted. Conclusions: Abiraterone acetate was well-tolerated and produced anti-tumor activity in heavily pretreated pts, as evidenced by PSA declines and improved PS. Incidence of mineralocorticoid-related AEs (HTN or hypokalemia) was reduced with the addition of low-dose prednisone. The keto-naïve post-docetaxel CRPC population was selected for the ongoing phase III pivotal study to confirm these results. [Table: see text]

Everolimus in combination with paclitaxel and carboplatin in patients with advanced melanoma: A phase II trial of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8556-8556
Author(s):  
Ralph J. Hauke ◽  
Jeffrey R. Infante ◽  
Kent C. Shih ◽  
Mark S. Rubin ◽  
Edward Arrowsmith ◽  
...  
Keyword(s):  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Entire Group ◽  
Combination Regimen ◽  
Eligibility Criteria ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps

8556 Background: The PI3k/AKT pathway is activated in most metastatic melanomas; mTOR is a critical component of this pathway. Everolimus, an mTOR inhibitor, has demonstrated single-agent activity in patients with advanced melanoma. We evaluated the efficacy and toxicity of everolimus in combination with paclitaxel/carboplatin in patients with advanced melanoma. Methods: Eligible patients had stage IV or unresectable stage III melanoma, unselected for braf status, previously untreated with chemotherapy or targeted agents. Previous immunotherapy was allowed. Additional eligibility criteria: ECOG PS 0 or 1; measurable disease; no active brain metastases; adequate bone marrow, kidney, and liver function; informed consent. All patients received paclitaxel 175mg/m2, 1-3 hour IV infusion, and carboplatin AUC 6.0 IV on day 1 of each 21-day cycle. Everolimus 5mg PO was given daily. Patients were evaluated for response every 6 weeks; treatment continued until progression or undue toxicity. Median progression-free survival (PFS) for paclitaxel/carboplatin treatment is 4 months; we looked for a median PFS of 6 months with this novel combination. Results: Seventy patients were treated between 2/2010 and 2/2011; median age 63, 90% had stage IV melanoma. 91% of patients received at least 2 cycles of therapy; median cycles received: 4 (range: 1-25+). Twelve patients (17%) had partial responses; an additional 42 patients (60%) had stable disease at first reevaluation. After a median 13 months of followup, the median PFS for the entire group was 4 months (95% CI: 2.8 – 5.0 months); 96% had progressed during the first 12 months. Median survival was 10 months (95% CI: 7.3 – 10.9 months). Toxicity was as previously described with these agents; neutropenia was the most common grade 3/4 toxicity (27%). Only 3 patients stopped treatment due to toxicity. Conclusions: The addition of everolimus to paclitaxel/carboplatin was feasible and well-tolerated; however, efficacy results were similar to those reported with paclitaxel/carboplatin alone. Further development of this combination regimen for treatment of metastatic melanoma is not recommended.

Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients (pts) with metastatic castrate resistant prostate cancer (mCRPC): Cohort B of the phase 1b/2 KEYNOTE-365 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Christophe Massard ◽  
Margitta Retz ◽  
Peter Hammerer ◽  
Fernando Quevedo ◽  
Peter C.C. Fong ◽  
...  
Keyword(s):  
End Points ◽  
Immune Mediated ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Pretreated Patients ◽  
Phase 1B ◽  
Grade 3 ◽  
Castrate Resistant

5029 Background: Pembro had activity as monotherapy in pretreated advanced mCRPC. Data are presented here from cohort B (pembro + docetaxel/prednisone) of KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study to test combinations in mCRPC. Methods: Pts who progressed on or became intolerant to ≥4 wk of abi or enza in the prechemotherapy mCRPC state and progressed within 6 mo before screening were eligible. Pts received pembro 200 mg IV with docetaxel 75 mg/m2 IV Q3W plus prednisone 5 mg orally twice daily. The primary end points were safety and PSA response rate (confirmed PSA decrease ≥50%). Key secondary end points were investigator-determined ORR (RECIST v1.1), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, rPFS, and OS. Results: 72 pts (median age, 68 y; visceral disease, 36%; measurable disease, 50%) began pembro + docetaxel. Median (95% CI) follow-up was 10 (8-12) mo. Efficacy is outlined in the table. Treatment-related AEs occurred in 69 (96%) pts; most frequent (≥30%) were alopecia (43%), fatigue (40%), and diarrhea (39%). Grade 3-5 treatment-related AEs occurred in 27 (38%) pts, including 2 deaths from treatment-related AEs (pneumonitis). Most commonly reported immune-mediated AEs were infusion-related reactions (11%) and colitis (10%). Conclusions: Pembro + docetaxel/prednisone has activity in pts with mCRPC who previously progressed on second-generation hormone therapy. AEs were considered mild for the treatment combination. Clinical trial information: NCT02861573. [Table: see text]

Pembrolizumab (pembro) in heavily pretreated metastatic castrate-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 255-255
Author(s):  
Marcus Marie Moses ◽  
Elisa Ledet ◽  
Charlotte Manogue ◽  
Brian E. Lewis ◽  
Pedro C. Barata ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Median Time ◽  
Predictive Biomarkers ◽  
The Other ◽  
Panel Testing ◽  
Heavily Pretreated ◽  
Clinical Annotation ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Ctdna Analysis

255 Background: KEYNOTE-199 has shown PSA responses of 11% to pembro in mCRPC. This study aims to further evaluate pembro in heavily pre-treated mCRPC patients (pts) correlating clinical outcomes with somatic and germline mutational burden. Methods: Single-institution retrospective analysis of mCRPC pts treated with pembro with germline panel testing and baseline ctDNA analysis using Guardant360 (Redwood City, CA). Baseline clinical annotation was collected and correlated with ctDNA data and clinical outcomes; ctDNA annotations included amplification (amp) and somatic mutation (mut; allele fraction ≥0.3%). Clinical outcomes were assessed after 3 cycles defined as: PSA≥50% PSA decline) or PSA≥30 response. Results: 27 mCRPC pts were treated with pembro between Oct 2016 and June 2018, median age 69 (56-82), 70% Caucasian, 26% African-American, and 4% Other, 70% Gleason 8-10, 59% bone-only, 22% bone+tissue, and 19% bone+LN metastases, were included. Pembro was given after a median 5 CRPC therapies with a median initial PSA of 76.1 ng/mL (4.85-1160), median treatment duration of 1.4 months (0-24.3). Prior treatments include abiraterone (n = 27), enzalutamide (n = 17), docetaxel (n = 19), and provenge (n = 16). 18 pts had ctDNA testing both pre- and post-pembro with a median time from testing to pembro of 0.9 months (0-3.9) and a median time from pembro to NGS testing of 0.7 months (0-2.6). Pre-pembro NGS had the following cfDNA alterations: 74% AR (mut = 8, amp = 8, both = 4), 55% TP53, and 0% DNA repair. ctDNA allelic fraction decrease occurred in 50% (6/12) of pts with AR mutations. 55% (15/27) of pts completed ≥3 cycles of pembro with the following responses: PSA≥50 13% and PSA≥30 20%. Two PSA complete responders (CR) (PSA < 0.01) had germline pathogenic alterations (BLM or MSH2). One of these pts was bone only; the other had radiographic CR. The MSH2 germline tumor was MSI-H and lacked MSH2/MSH6 on immunohistochemistry. The other PSA CR was not assessed given limited tissue. Conclusions: 33% of pts evaluated, achieved a PSA decline of ≥30% al response or greater signifying there is a subset of mCRPC pts that can benefit from pembro. Further evaluation is necessary to determine predictive biomarkers for this patient population.

Sign in / Sign up

Export Citation Format

Share Document