Early progression (progr) in patients (pts) with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation (gBRCAm): Phase III POLO trial of olaparib (O) versus placebo (P).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 750-750
Author(s):  
Teresa Macarulla ◽  
Hedy L. Kindler ◽  
Pascal Hammel ◽  
Michele Reni ◽  
Eric Van Cutsem ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Brca Mutation ◽  
Standard Of Care ◽  
Complete Response ◽  
Small Sample ◽  
Phase Iii ◽  
Stepwise Logistic Regression ◽  
Continuous Variables ◽  
Platinum Based Chemotherapy ◽  
Stepwise Logistic Regression Model

750 Background: In POLO (NCT02184195), maintenance O was associated with significant progr-free survival benefit vs P in pts with a gBRCAm and mPaC (Golan NEJM 2019). Early progr or death (within 4 months [m]) occurs in ~35−45% of pts on standard-of-care first-line (1L) chemotherapy for mPaC (Conroy NEJM 2011; von Hoff NEJM 2013); however, predictive factors are currently unknown and early progr has not been addressed in the maintenance setting. We examined factors potentially associated with early progr in POLO. Methods: Following ≥16 weeks of 1L platinum-based chemotherapy (PBC) without progr, pts were randomized to maintenance O (tablets; 300 mg bd) or P until progr or unacceptable toxicity. Early progr was defined as progr (by blinded independent central review) or death within 4 m of randomization. A stepwise logistic regression model included baseline (BL) factors age, albumin, lactate dehydrogenase (LDH), global health status (GHS) and physical functioning (PhysF) as continuous variables, and discrete variables listed in the Table. Results: 62/154 randomized pts (40%) were defined as early progressors (EP; Table). Due to missing BL data, the multivariate analysis included 127 pts (56 EPs [44%]). Lower BL PhysF score (continuous) was significantly associated with early progr ( P= 0.02); no difference for partial/complete response (PR/CR) vs stable disease (SD). Conclusions: While small sample size limited analysis power, PhysF score was the only BL factor significantly associated with early progr in pts with a gBRCAm and mPaC in the POLO trial of maintenance O vs P. Clinical trial information: NCT02184195 . [Table: see text]

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

The role of 68Ga-DOTATATE for evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 217-217
Author(s):  
Mehmet Asim Bilen ◽  
Akinyemi A Akintayo ◽  
Olayinka A. Abiodun-Ojo ◽  
Omer Kucuk ◽  
Bradley Curtis Carthon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Cell Cancer ◽  
Standard Of Care ◽  
Small Sample ◽  
Bone Lesions ◽  
Care Treatment ◽  
Platinum Based Chemotherapy ◽  
Standard Of Care Treatment

217 Background: Neuroendocrine transformation (NE) of prostate cancer is difficult to diagnose and treat. 68Ga-DOTATATE PET is useful to detect well-differentiated neuroendocrine tumors, but its application in prostate cancer is not well understood. We evaluated DOTATATE PET in patients with mCRPC and suspected or known NE. Methods: DOTATATE PET/CT were performed in 17 patients with mCRPC. Summed SUVmax of up to 5 bone and 5 soft tissue lesions in each patient were correlated with histologic presence of NE and response to standard of care treatment and clinical outcome (NCT03448458). Results: Mean age was 62.3±9.2 years. Median PSA was 39.0 ng/ml. 2/17 patients had biopsy proven NE. 1/17 was found to have squamous cell cancer and therefore excluded from analysis. 2 patients with NE had platinum-based chemotherapy. Of the 14 patients without NE, 7/14 received enzalutamide or abiraterone, and 7/14 received taxane based chemotherapy after DOTATATE PET. On PET, all patients had at least one lesion (median 7 [interquartile range 6-9]) with uptake. 11/16 patients had bone and visceral/nodal lesions, 4/16 had only bone lesions, and 1 had only nodal disease. Summed SUVmax was significantly higher in 2/16 patients with proven NE compared to the 14/16 non-NE patients (99.1± 16.5 ng/ml vs 48.4± 40.6 ng/ml; p=0.04). There was no correlation between summed SUVmax and PSA. Follow-up was available in 15/16 patients. SUVmax was higher in patients who did not respond to treatment, however, the trend was non-significant (69.5 ± 46.6 vs 39.3 ± 29.6; p=0.20). There was no significant association between survival and DOTATATE uptake. 6/16 patients had next generation sequencing. Of these, 1 patient without NE had BRCA2 mutation, and also had the highest summed uptake in this study. Conclusions: DOTATATE uptake is higher in mCRPC patients with NE or with BRCA mutation. Uptake was higher in patients who did not respond to standard of care treatment, though this was a nonsignificant trend, possibly due to small sample size. Larger studies are therefore recommended. Clinical trial information: NCT03448458.

Outcome of children with malignant germ cell tumors by response status at the end of induction chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10023-10023
Author(s):  
Adriana Fonseca ◽  
Doojduen Villaluna ◽  
Mark D. Krailo ◽  
A. Lindsay Frazier ◽  
Furqan Shaikh
Keyword(s):  
Germ Cell ◽  
Induction Chemotherapy ◽  
Small Sample Size ◽  
Germ Cell Tumors ◽  
Response Assessment ◽  
Complete Response ◽  
Small Sample ◽  
Phase Iii ◽  
Salvage Regimen ◽  
Malignant Germ Cell Tumors

10023 Background: The management of pediatric malignant germ cell tumors (MGCTs) includes induction therapy with 3-4 cycles cisplatin, etoposide, bleomycin (PEb). The current practice recommends 2-3 cycles of PEb (total 6 cycles) as consolidation therapy if response is not complete at the end of induction, a significantly different approach than that used in adult patients who receive a standard number of cycles. Furthermore, there is no evidence supporting the addition of a consolidation phase with PEb in pediatric patients with MGCTs. Methods: We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs (AGCT0132). All patients received 3 cycles of PEb and underwent response assessment at the end of induction. Complete Response (CR) was defined as negative tumor markers and no viable residual lesion. Patients in CR were not to receive any further chemotherapy. Patients not in CR were prescribed 3 additional cycles of PEb as consolidation. Event-free survival (EFS) and Overall survival (OS) was calculated using the Kaplan-Meier method. Results: Among 210 patients enrolled, 193 patients had CR after 3 cycles of induction chemotherapy, and their post-induction 4yr-EFS and OS was 93% and 99%. Fifteen patients were not in CR at the end of the first 3 cycles and received additional chemotherapy, and their 4yr-EFS and OS was 51% and 60%. Conclusions: Children with MGCTs who have a partial response after the first 3 cycles of chemotherapy had an inferior outcome compared to those with a CR, despite receiving additional cycles of PEb chemotherapy. Thus, we conclude that consolidation is of unclear benefit. Although our results are limited by small sample size and lack of comparator, we propose that pediatric MGCT patients who fail to achieve a CR after standard induction chemotherapy should receive a salvage regimen with different agents rather than consolidation with more cycles of the same chemotherapy.

scholarly journals Advances in the systemic treatment of triple-negative breast cancer

2018 ◽  
Vol 25 ◽  
pp. 142 ◽  
Author(s):  
J.M. Lebert ◽  
R. Lester ◽  
E. Powell ◽  
M. Seal ◽  
J. McCarthy
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Systemic Treatment ◽  
Brca Mutation ◽  
Pathologic Complete Response ◽  
Standard Of Care ◽  
Complete Response ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting

Triple-negative breast cancer constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. Molecular characterization, while not a standard of care, can further subtype triple-negative breast cancer and provide insight into prognostication and behaviour. Optimal chemotherapy regimens have yet to be established; however, there have been advances in the systemic treatment of triple-negative breast cancer in the neoadjuvant, adjuvant, and metastatic settings. In this review, we discuss evidence for the potential benefit of neoadjuvant platinum-based chemotherapy, adjuvant combination chemotherapy with weekly paclitaxel, and BRCA mutation–directed therapy in the metastatic setting. The role for adjuvant capecitabine in patients who do not achieve a pathologic complete response with neoadjuvant chemotherapy is reviewed. Future directions and data concerning novel targeted agents are reviewed, including the most recent data on parp [poly (adp-ribose) polymerase] inhibitors, antiandrogen agents, and immunotherapy.

Abstract W P224: Higher Pre-Hospital Blood Pressure Prolongs Door to Needle Thrombolysis Times

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Digvijaya Navalkele ◽  
Chunyan Cai ◽  
Mohammad Rahbar ◽  
Renganayaki Pandurengan ◽  
Tzu-Ching Wu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Small Sample Size ◽  
Heart Association ◽  
Small Sample ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Intravenous Tissue Plasminogen Activator ◽  
Number Of Patients

Background: Per American Heart Association guidelines, blood pressure (BP) should be < 185/110 to be eligible for intravenous tissue plasminogen activator (tPA). It is shown that door to needle (DTN) time is prolonged in patients who require anti-hypertensive medications prior to thrombolysis in the emergency department (ED). To our knowledge, no studies have focused on pre-hospital BP and its impact on DTN times. We hypothesize that DTN times are longer for patients with higher pre-hospital BP. Methods: We conducted a retrospective review of acute ischemic stroke patients who presented between 1/2010 and 12/2010 to our ED through Emergency Medical Services (EMS) within 3-hrs of symptom onset. Patients were identified from our registry and categorized into two groups: Pre-hospital BP ≥ 185/110 (Pre-hsp HBP) and < 185/110 (Pre-hsp LBP). BP records were abstracted from EMS sheets. Two groups were compared using two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. Results: A total of 107 consecutive patients were identified. Out of these, 75 patients (70%) were treated with tPA. Among the patients who received thrombolysis, 35% had pre-hospital BP ≥ 185/110 (n= 26/75). Greater number of patients required anti-hypertensive medications in ED in high BP group compared to low BP group (Pre-hsp HBP n= 14/26, 54%; Pre-hsp LBP n= 13/49, 27%, p < 0.02). Mean door to needle times were significantly higher in Pre-hsp HBP group. (mean ± SD 87.5± 34.2 Vs. 59.7±18.3, p<0.0001). Analysis of patients only within the Pre-hsp HBP group (n= 26) revealed that DTN times were shorter if patients received pre-hsp BP medications compared to patients in the same group who did not receive pre-hsp BP medication (n= 10 vs 16; mean ± SD 76.5 ± 25.7 Vs. 94.3 ± 37.7, p = 0.20) Conclusion: Higher pre-hospital BP is associated with prolonged DTN times and it stays prolonged if pre-hospital high BP remains untreated. Although the later finding was not statistical significant due to small sample size, pre-hospital blood pressure control could be a potential area for improvement to reduce door to needle times in acute ischemic stroke.

The feasibility of same day pegfilgrastim-cbqv administration in breast cancer patients receiving myelosuppressive chemotherapy regimens at a northern Virginia cancer center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18687-e18687
Author(s):  
Maya Leiva ◽  
Angela Pennisi ◽  
Kathleen Kiernan Harnden ◽  
Patricia Conrad Rizzo ◽  
Lauren Ann Mauro
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Small Sample Size ◽  
Standard Of Care ◽  
Secondary Prophylaxis ◽  
Small Sample ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Curative Intent ◽  
Myelosuppressive Chemotherapy

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.

scholarly journals Discrepancy of Blast Percentage between the Bone Marrow Aspirate and Flow Cytometry and Its Impact on Survival Outcomes in Patients with Myelodysplastic Syndromes Excess Blast (MDS-EB)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5441-5441
Author(s):  
Meera Yogarajah ◽  
Phuong L. Nguyen ◽  
Rong He ◽  
Hassan B. Alkhateeb ◽  
Mithun Vinod Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Small Sample Size ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Risk Groups ◽  
Small Sample ◽  
International Prognostic Scoring System ◽  
P Value ◽  
Number Of Patients

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

scholarly journals Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Deborah M. Stephens ◽  
Ken Boucher ◽  
Elizabeth Kander ◽  
Sameer A. Parikh ◽  
Erin M. Parry ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hodgkin Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Small Sample Size ◽  
Case Series ◽  
Standard Of Care ◽  
Median Number ◽  
Small Sample ◽  
Lymphocytic Leukemia ◽  
Treatment Type

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was 1 (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95%CI 62-83%). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; p=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.

Methylated DNA markers for monitoring palliative chemotherapy response in advanced colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15511-e15511
Author(s):  
Mojun Zhu ◽  
Douglas W. Mahoney ◽  
Kelli Burger ◽  
Patrick H. Foote ◽  
Karen A. Doering ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Response ◽  
Systemic Therapy ◽  
Small Sample Size ◽  
High Sensitivity ◽  
Response Assessment ◽  
Small Sample ◽  
Chemotherapy Response ◽  
Continuous Variables ◽  
Methylated Dna

e15511 Background: Aberrantly methylated DNA marker (MDM) candidates are strongly associated with primary colorectal cancer (CRC) before treatment and detect CRC recurrence with high sensitivity when assayed from plasma. The relationship of these MDMs in association to chemotherapy treatment response is unknown. Methods: In a prospective cohort of patients receiving systemic therapy for advanced CRC, peripheral blood was collected serially during restaging visits. 15 patients were retrospectively identified to have partial response (PR), stable disease (SD) and progressive disease (PD) to treatment (n=5 for each group) based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Using paired samples from each patient before and after response assessment, we analyzed 11 MDMs ( GRIN2D, ZNF671, ANKRD13B, QKI, VAV3, JAM3, SFMBT2, CHST2, ZNF568, FER1L4 and CNNM1) to assess correlation with treatment response. Cell-free DNA was extracted and bisulfite treated before MDMs were quantified by target enrichment long-probe quantitative-amplified signal assay and normalized to a methylated sequence of B3GALT6. Continuous variables are summarized as a median with corresponding interquartile ranges (IQR) and comparisons between subgroups were based on the Wilcox Rank Sums test. Results: The median interval between pre- and post-response assessment visits was 69 days (IQR: 63-83 days) and the level of tumor burden at pre-assessment was similar across all response types (Table 1). Patients with PD had higher levels of methylated GRIN2D, ZNF671 and ANKRD13B than those with PR or SD at baseline and may offer additional prognostic value over CEA which was similar in the PR and PD groups before treatment (Table 1). Elevation of pre-assessment MDMs preceded radiographic evidence of disease progression by 82 days (IQR 69-83 days). Conclusions: Three MDMs, GRIN2D, ZNF671 and ANKRD13B, were found to reflect treatment response (PD vs. PR + SD) as shown in the table. Although this pilot study was limited by a small sample size, it demonstrated the feasibility of using plasma-based MDMs in monitoring treatment response to systemic therapy for advanced CRC and should be compared to CEA in a larger study.[Table: see text]

scholarly journals Efficacy and safety of darolutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a sub-group analysis of the phase III ARAMIS trial

2020 ◽  
Author(s):  
Hiroji Uemura ◽  
Hisashi Matsushima ◽  
Kazuki Kobayashi ◽  
Hiroya Mizusawa ◽  
Hiroaki Nishimatsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Sample Size ◽  
Group Analysis ◽  
Specific Antigen ◽  
Japanese Patients ◽  
Small Sample ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Abstract Background Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. Methods In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. Results In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11–0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. Conclusions Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.

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