Association of CD133 polymorphisms and clinical outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with either first-line 5-FU + bevacizumab (BV) or second-line irinotecan (IR)/cetuximab (CB) or IR alone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4062-4062
Author(s):  
A. Pohl ◽  
W. Zhang ◽  
D. Yang ◽  
G. Lurje ◽  
Y. Ning ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
Clinical Outcome ◽  
Phase Iii ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Log Rank Test ◽  
Line Setting

4062 Background: CD133 has been routinely used to identify colon cancer stem cells. A recent study indicated that elevated levels of CD133 plasma mRNA correlated with colon cancer recurrence. Furthermore plasma levels of CD133+ progenitor cells have been found to be decreased after treatment with BV. We tested whether potentially functional frequently occurring germline variations in the 3’UTR-region of the CD133 gene (rs2240688, rs3130 and rs2286455), might be associated with clinical outcome in first- and second-line treated mCRC pts. Methods: Genomic DNA was extracted either from peripheral blood (79 pts, who were enrolled in a phase-II clinical trial with FOLFOX/BV or XELOX/BV) or formalin-fixed paraffin-embedded tumor samples (186 pts, who were enrolled in the EPIC phase III clinical trial, US-sites only) of mCRC pts. Pts received either first-line treatment with FOLFOX/ BV (33 pts) or XELOX/BV (46 pts) or second-line treatment with CB/IR (84 pts, arm A) or IR (102 pts, arm B) alone. Genotyping was performed using PCR-RFLP assays. Results: 79 pts (47 men, 32 women) received FOLFOX/BV or XELOX/BV. Radiologic response: 43 pts (54%) CR/PR, 35 pts (45%) SD/PD. Median PFS was 10.8 months (95%CI: 8.1–14.9). The second cohort consisted of 186 pts (103 men, 83 women). Radiologic response: Arm A 11 pts (13%) CR/PR, 73 pts (87%) SD/PD. Arm B 6 pts (6%) CR/PR, 96 pts (94%) SD/PD. Median PFS (arm A) was 3.0 months (95%CI: 2.4–4.1) vs. 2.7 months (arm B,95%CI: 2.2–2.9). Combined analysis of rs2286455 and rs3130 showed a significant association with PFS (p= 0.010, log-rank test) in pts receiving FOLFOX/BV or XELOX/BV. In pts receiving IR alone rs2240688 was significantly associated with OS (p=0.0128, log-rank test). Multivariate analysis showed a significant association with PFS in first-line setting for rs2286455 and rs3130 (adjusted p=0.012) and a trend in second-line setting for rs2240688 (adjusted p=0.086). Conclusions: These are the first data to show that polymorphisms in CD133 predict outcome in mCRC pts in first- and second- line setting, suggesting that CD133 may be a potential predictive marker. These results need to be confirmed in larger prospective studies. [Table: see text]

A review of the patterns of docetaxel use for hormone refractory prostate cancer (HRPC) at the Princess Margaret Hospital

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16161-e16161
Author(s):  
S. N. Chin ◽  
L. Wang ◽  
A. Lau ◽  
M. Moore ◽  
S. S. Sridhar
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Median Duration ◽  
Response Rates ◽  
Routine Clinical Practice ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line

e16161 Background: Docetaxel is standard of care for the treatment of HRPC, based on two large randomized clinical trials. The aim of this study was to determine if docetaxel use and effectiveness in routine clinical practice was similar to that seen in the TAX 327 randomized phase III clinical trial. Methods: A retrospective chart review was undertaken to assess patterns of docetaxel use for HRPC at our institution for the 2-year period since its approval for the first-line treatment of HRPC in 2005. Results: Eighty-eight patients, median age 71 and baseline PSA 107, received docetaxel in the first line setting. Main reasons for initiating docetaxel were rising PSA (90%) and progressive symptoms (71%). Eighteen percent of patients received docetaxel for rising PSA alone. A median of 7 cycles was administered. PSA response rates were 61%, time to response 1.5 months, and response duration 6.8 months. Disease progression was the most common reason for treatment discontinuation (36%). Main toxicities were fatigue (32%) and neuropathy (22%). Kaplan Meier survival analysis showed median duration of survival was 15.9 months (95% CI 12.4–20.5) from first drug use. 1-year survival was 0.63 (95% CI 0.52–0.72). Post-docetaxel, 36 patients received second-line treatment, mostly with mitoxantrone (89%). Second-line response rates were 22%, and median duration of response was 4 months. Conclusions: In routine clinical practice, docetaxel is a well-tolerated regimen for the treatment of HRPC. Response rates and toxicity profiles were comparable to the randomized trials. However, compared with the TAX 327 clinical trial, survival was slightly shorter than expected (15.9 vs. 18.9 months), possibly due to inclusion of patients with poorer performance status and comorbidities, who may be excluded from clinical trials. Second-line response rates were also comparable with previous reports. No significant financial relationships to disclose.

Multicenter phase II clinical trial of everolimus in Japanese patients with unresectable or metastatic renal cell carcinoma (mRCC) after failure of treatment with first-line tyrosine kinase inhibitor (TKI) therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 455-455
Author(s):  
Seiichiro Ozono ◽  
Masafumi Oyama ◽  
Masahiro Nozawa ◽  
Kiyohide Fujimoto ◽  
Ken Kishida ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Line Setting

455 Background: Everolimus has shown the efficacy and the safety in the phase III trial (RECORD-1) in patients with mRCC after failure of Vascular Endothelial Growth Factor Receptor-TKI. However, 26% of patients received two TKIs (sunitinib and sorafenib) as previous therapy in RECORD-1. In addition, as pre-treatment before TKI, 65% of patients received cytokine therapy and 13% of patients received chemotherapy. Therefore, there is still no clear evidence of everolimus as second line setting after failure of 1st-line TKI therapy. Methods: This study is an open-label, multi-center, single-arm, phase II trial. Primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, objective response rate, time-to-treatment-failure, safety and quality of life (EORTC QLQ-C30, FKSI-DRS, EQ-5D). Key eligibility criteria are RCC with clear cell component, patients who received one TKI as first line therapy, patients who did not receive cytokine and chemotherapy and ECOG performance status 0-1. Results: 57 patients were enrolled from 02/11 to 12/12. Median age was 63 years, common sites of metastasis were lung (32.7%) and bone (12.2%), 79.6% had previous nephrectomy, previous TKI therapy were sunitinib (69.4%), sorafenib (22.4%) and axitinib (8.2%). Median PFS was 4.4 months (95% confidence interval: 3.7-6.0). 8.2% had partial response and 57.1% had stable disease according to RECIST v.1.0. The incidence of adverse events (AEs) of all grades was 95.9%. Major AEs were stomatitis (49.0%), hypertriglyceridemia (26.5%) and hypercholesterolemia (24.5%). Serious AEs were stomatitis (10.2%), interstitial lung disease (6.1%) and rash (6.1%). There were no treatment related deaths. All QOL scores were not changed at 2 months, while dyspnea and global health scores of EORTC QLQ-C30 and FKSI-DRS score were worsened at 4 months. Conclusions: This study is a first report of everolimus as second line setting after failure of 1st-line TKI. Further study and long-term follow-up would be warranted. Clinical trial information: UMIN000004742.

scholarly journals Venetoclax-Based Regimen for Treatment of Patients with Acute Myeloid Leukemia in Community Based Practices

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5081-5081
Author(s):  
Lisa Y Law ◽  
Ryan Stevenson ◽  
Gwendolyn Ho ◽  
Bijay Nair ◽  
Asakura Laura ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Hypomethylating Agent ◽  
Third Line ◽  
Line Setting ◽  
Acute Myeloid

Introduction: There are limited options for acute myeloid leukemia (AML) patients who are too frail to receive intensive induction chemotherapy or who have relapsed /refractory disease. Early phase II trials published in 2016 demonstrated promising outcomes in AML with the BCL-2 inhibitor venetoclax, which was FDA approved in November 2018. We conducted a retrospective review of AML patients who received venetoclax at Kaiser Permanente Northern California (KPNC) specifically examining patients' characteristics and outcomes. Methods: This is a retrospective review of all KPNC patients who had a diagnosis of AML and received at least 1 prescription of venetoclax from January 1, 2016 through March 31, 2019. Data was abstracted from our electronic medical record. Variables included age, complete blood count, AML type, lines of therapy, prior use of hypomethylating agent, cytogenetics, somatic mutation, duration of treatment and chemotherapy regimen. Because none of the patients were treated under clinical trial protocol, most did not have a scheduled bone marrow biopsy to formally document disease status. Hematologic response (HR), defined here as neutrophil ≥ 0.5 x 109/L, platelet ≥ 50 x 109/L and RBC transfusion independence was used to access treatment effectiveness. Results were analyzed via descriptive statistics. Results: A total of 68 patients received venetoclax-based chemotherapy for treatment of AML. The median age was 68 (range 12-87). Among those 68 patients, 35% had venetoclax-based treatment as first line therapy, 35% as second line, and the remaining as third or later line (Table 1). Among those who received venetoclax as first line treatment, 58% had a HR. Among those who received venetoclax as second line treatment, 29% had a HR and 43% of those went on to allogeneic bone marrow transportation (BMT). 20% of those that received venetoclax in the third line setting had a HR and all went on to BMT. Patients who received venetoclax in fourth line or above did not have any significant response. Only 2 out of the 16 patients who received prior hypomethylating agent responded to venetoclax combination therapy. Four patients did not even complete cycle 1. 12 out of 68 patients were prescribed venetoclax based on FDA approved guidelines in November 2018. Of those 75% demonstrated HR. Conclusion While most of our patients used off-label venetoclax in a non-clinical trial setting, we confirm that venetoclax-based regimen is an effective treatment for AML, similar to published data. Our cohort represents a more heterogeneous population, which is more generalizable to the community. There is a higher response rate among those who used it in the first- and second-line setting (58% and 29% respectively). Venetoclax also showed efficacy in the second- or third-line setting, bridging patients to allogeneic BMT. Patients with prior hypomethylating agent are less likely to benefit from this drug. Venetoclax in combination with a hypomethylating agent is an effective AML regimen. Its efficacy deserves further studies, perhaps as a front-line treatment, sparing patients from intensive toxic inpatient induction chemotherapy. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: This retrospective study evaluates the use of venenoclax-based regimen for treatment of AML. Clinicians have been using it since 2016, but the drug was not formally FDA approved for AML until November 2018.

scholarly journals Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

2021 ◽  
Author(s):  
B. González Astorga ◽  
F. Salvà Ballabrera ◽  
E. Aranda Aguilar ◽  
E. Élez Fernández ◽  
P. García-Alfonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Option ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Effective Therapeutic Option ◽  
Line Setting ◽  
First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

Oxaliplatin Plus Irinotecan Compared With Irinotecan Alone as Second-Line Treatment After Single-Agent Fluoropyrimidine Therapy for Metastatic Colorectal Carcinoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4544-4550 ◽  
Author(s):  
Daniel G. Haller ◽  
Mace L. Rothenberg ◽  
Alfred O. Wong ◽  
Piotr M. Koralewski ◽  
Wilson H. Miller ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Single Agent ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Sensory Disturbances ◽  
Previously Treated ◽  
Grade 3

Purpose To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. Patients and Methods A phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m2 plus oxaliplatin 85 mg/m2) or irinotecan alone (350 mg/m2) every 3 weeks. Results At the data cutoff (when 447 of 628 randomly assigned patients had died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related symptoms (32% v 19%, respectively; P = .0072) were also improved with IROX as compared with irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable between the IROX and irinotecan groups, respectively. Conclusion IROX is an effective treatment for metastatic CRC that has progressed after first-line fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone, providing an additional option in the postadjuvant or second-line treatment setting for patients who experience treatment failure with single-agent fluoropyrimidine therapy.

Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Paul E. Goss ◽  
Kathrin Strasser
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Clinical Status ◽  
Phase Iii ◽  
Type I ◽  
Third Generation ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Third

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

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