Three lines of targeted therapy for metastatic renal cell carcinoma (mRCC): A viable strategy?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15581-e15581
Author(s):  
Tomas Buchler ◽  
Zbynek Bortlicek ◽  
Alexandr Poprach ◽  
Katerina Kubackova ◽  
Igor Kiss ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
National Database ◽  
Rank Test ◽  
Targeted Agents ◽  
Line Therapy ◽  
Targeted Agent

e15581 Background: Sequential therapy with tyrosine kinase inhibitors (TKIs) and the mTOR inhibitor everolimus has been proposed for mRCC. The aim of the present retrospective analysis was to compare the efficacy of everolimus used after one versus two prior TKIs and to assess the progress of a defined cohort of patients (pts) through sequential lines of therapy. Methods: In the national database of mRCC pts treated with targeted agents 368 pts received everolimus as the 2nd (N=269) or 3rd (N=99) targeted agents following TKIs sunitinib or sorafenib. Survival was calculated using the Kaplan-Meier method, and the differences were assessed using the Log-rank test. Furthermore, the treatment course was evaluated in 331 mRCC pts starting 1st line therapy with sunitinib or sorafenib in 2010. The data cut-off date was October 8, 2012. Results: Progression-free survival (PFS) for everolimus in the 2nd versus the 3rd line of targeted therapy was 6.5 months (95% confidence interval [95% CI] 5.3-7.7 months) versus 6.1 months (95% CI 4.0-8.3 months), respectively (P=0.159). The incidence and profile of adverse events were similar in both lines. PFS from the start of the first targeted agent to progression on the third targeted agent was similar for pts receiving three lines of therapy using the TKI-TKI-mTOR (N=99) and TKI-mTOR-TKI (N=17) sequence: 28.5 months (95% CI 25.2-31.7 months) versus 27.2 months (95% CI 24.0-30.4 months), respectively (P=0.281). The median follow-up for the initial cohort of 331 pts treated with sunitinib or sorafenib was 20.1 months. 152 pts (46%) subsequently received a 2nd line therapy, and 82 pts (25%) died before reaching the 2nd line. Of the 152 pts receiving the 2nd line therapy, only 38 pts (11%) went on to the 3rd line, and 46 pts (14%) died before reaching the 3rd line of therapy. The remaining pts still continued on 1st line (N=50; 15%) or 2nd line therapy (N=34; 10%), were lost to follow-up (N=30; 9%), or were alive but not receiving antineoplastic treatment (N=51; 15%). Conclusions: Everolimus has similar efficacy and toxicity whether used in the 2nd or the 3rd line of targeted therapy for mRCC. A minority of mRCC pts starting the 1st line targeted treatment can be expected to reach the 3rd line therapy.

scholarly journals LGG-03. LONG-TERM FOLLOW UP OF TARGETED THERAPY IN PEDIATRIC LOW-GRADE GLIOMAS: THE DANA-FARBER/BOSTON CHILDREN’S EXPERIENCE

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Jessica Tsai ◽  
Jayne Vogelzang ◽  
Cecilia Sousa ◽  
Kee Kiat Yeo ◽  
Keith Ligon ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Natural History ◽  
Low Grade ◽  
Targeted Agents ◽  
First Line ◽  
Therapy Initiation ◽  
Line Therapy ◽  
History Of ◽  
Targeted Agent

Abstract Background Pediatric low grade gliomas (pLGGs) are the most common central nervous system (CNS) tumor in children and characterized by alterations in the MAPK pathway. Standard of care is not well defined, and treatment has evolved over the last decade to include molecular targeted therapies. The impact of targeted agents on the natural history of pLGGs remains unknown. We present a retrospective review of patients receiving targeted agents integrated with molecular profiling. Methods We performed an IRB-approved, retrospective chart review of pLGGs treated with off-label use of dabrafenib, vemurafenib, everolimus, and trametinib at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center from 2010 to 2020. Results Forty-nine patients were identified (dabrafenib n=9, everolimus n=27, trametinib n=10, and vemurafenib n=3). All patients receiving BRAF inhibitors harbored BRAF V600E mutation. Targeted agent was used as first-line therapy for 25% of patients, while for 31% of patients, targeted agent was second-line therapy. The median time from diagnosis to targeted therapy initiation was 4.76 years (0.10 – 23.77), median duration of targeted therapy was 0.79 years (0.01 – 4.87), median time to subsequent therapy post first-line targeted therapy was 0.2 years (0.01 – 3.33), and overall median follow-up for the entire cohort was 3.09 years (0.36 – 11.87). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation was 58.0%, 32.2%, and 26.9%, respectively. Survival analyses by molecular subgroup and agent were performed. Reasons for cessation of targeted therapy included toxicities, progression, and/or planned end of therapy. Conclusions Further efforts are ongoing to perform volumetric analysis of growth rates before, during, and after treatment. While targeted molecular therapies show great promise, it will be critical to understand how these agents alter the natural history of pLGGs, particularly in the context of genomic profiling.

A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14006-e14006
Author(s):  
Xiaotong Duan ◽  
Xiaoxia Zhu ◽  
Lijuan Wang
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Progression Free Survival ◽  
Driver Gene ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Nsclc Patients

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

Characterization of BCL-2 alternative proteins and outcome in patients with peripheral T-cell lymphoma (PTCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19531-e19531
Author(s):  
Mario L. Marques-Piubelli ◽  
Luisa Maren Solis ◽  
Luis Malpica ◽  
Sushant Gouni ◽  
Ranjit Nair ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Rank Test ◽  
Cell Transplant ◽  
Functional Studies ◽  
Tissue Biopsy ◽  
Previously Treated

e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identification of biologically rational targets, which may translate into effective and non-toxic treatment strategies, is a high priority. The pro-survival BCL-2 family members BCL-2, BCL-XL (BCL2L1), BCL-W (BCL2L2), BCL2A1 and MCL-1 contribute to tumor maintenance, progression, and chemo-resistance across a range of cancers, but their contributions in PTCL, NOS are poorly understood. Methods: Patients with PTCL, NOS treated between 09/2000 and 09/2019 and with available tissue biopsy were included in the study. Diagnosis was retrospectively confirmed by two expert hematopathologists. BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 expression was assessed by immunohistochemistry (IHC), and the percentage of positive tumor cells assessed by standard microscopy. The 2014 Lugano Classification was used to define response to therapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and were compared using log-rank test between patient groups. Results: Twenty-seven patients were included in the study: 67% were male, 52% ≥ 65 year old, and 48% had stage IV disease; 59% were previously treated and 41% received > 2 lines of therapy, including stem cell transplant (SCT) in 19%. The median expression of BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 by IHC was: 30% (range: 0-100%), 10% (range: 0-90%), 100% (range: 40-100%), 20% (range: 0-90%), and 70% (range: 1-100%), respectively. BCL-2A1 was significantly higher in previously treated patients (35% vs 5%, p = 0.02), and in those who had previously received > 2 lines of therapy (40% vs 5%, p = 0.02). Twenty-four (89%) patients were treated after tissue biopsy, 17 (63%) with chemotherapy, 7 (26%) with biological therapy, and 6 (22%) received subsequent SCT. Five (24%) patients achieved complete remission (CR); only BCL-W associated with response, a higher expression (quartiles 3 and 4) being observed among patients not achieving CR (median 100% vs 90%, p = 0.07). After a median follow-up of 28 months (95% CI, 14-42 months), 22 (81%) patients progressed or died, and median PFS was 4 months (95% CI, 2-6 months); only BCL-W associated with PFS, a shorter median PFS being observed for patients with higher expression (3 months vs 7 months, p = 0.001). At most recent follow-up, 17 (63%) patients died, and median OS was 6 months (95% CI, 1-12 months). only BCL-W associated with OS, a shorter median OS being observed for patients with higher expression (4 months vs not reached, p = 0.004). Conclusions: High expression of BCL-W associates with significantly worse outcome in patients with PTCL, NOS. While clinical trials investigating the safety and efficacy of BCL-2 inhibition in PTCL, NOS are ongoing, these results suggest that concomitant BCL-W inhibition may be beneficial, and functional studies aimed at confirming these findings are highly needed.

TACTICS: Final overall survival (OS) data from a randomized, open label, multicenter, phase II trial of transcatheter arterial chemoembolization (TACE) therapy in combination with sorafenib as compared with TACE alone in patients (pts) with hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 270-270
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Masafumi Ikeda ◽  
Takuji Torimura ◽  
Hiroshi Aikata ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Sequential Therapy ◽  
Combination Group ◽  
Targeted Agents ◽  
Primary Analysis ◽  
Open Label ◽  
Free Survival ◽  
Systemic Treatments ◽  
Conventional Tace ◽  
Post Trial

270 Background: To date many trials have been conducted to compare the efficacy and toxicity between TACE plus molecular targeted agents and TACE alone; all of them failed to show its clinical benefit in terms of progression free survival (PFS) or OS. In TACTICS trial (NCT01217034) TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. ( Gut 2020;69:1374-1376). Here we will report a final OS analysis from TACTICS trial with predefined mature OS events. Methods: Patients with unresectable HCC were randomized to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg twice daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumor progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is defined as TTUP, or time to any cause of death and OS. Multiplicity was adjusted by gatekeeping hierarchical testing. Results: At the cut-off date of July 31, 2020, 131 OS events were observed. Median OS was 36.2 mo with TACE plus sorafenib vs 30.8 mo with TACE alone (HR, 0.861 [95%CI, 0.607, 1.223]; P=0.40). ΔOS was 5.4 mo. Updated PFS was 22.8 mo with TACE plus sorafenib vs 13.5 mo with TACE alone (HR, 0.661[95%CI, 0.466, 0.938]; P=0.02). Post-trial treatments with active procedures/agents were observed in 47 (58.8%) in TACE plus sorafenib and in 58 (76.3%) with TACE alone. Anticancer procedures in TACE alone group include resection/ablation in 14, transarterial therapy in 53 and radiation in 7. Anticancer medications in TACE alone include targeted agents in 40 (29 sorafenib, 5 regorafenib, 3 lenvatinib, 3 ramucirumab), other systemic chemotherapy in 5 and immunotherapy in 5. Safety was consistent with the primary analysis, with no new signals identified. Conclusion: In TACTICS, TACE plus sorafenib did not show OS benefit as compared with TACE alone although significantly better PFS was consistently observed. OS in TACE plus sorafenib in TACTICS trial showed the longest OS (36.2 mo) with the longest ΔOS (5.4 mo) as compared with the previous 5 TACE combination trials. The major reason for negative OS result was speculated that many post-trial active treatments were performed in control arm (76.3%), which implies that OS endpoint in TACE combination trial may not be feasible anymore in current era of sequential therapy with many active locoregional and systemic treatments. Clinical trial information: NCT01217034.

scholarly journals Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versusHER2-directed therapies

2020 ◽  
Vol 12 ◽  
pp. 175883592093609
Author(s):  
Jiebai Zhou ◽  
Ning Ding ◽  
Xiaobo Xu ◽  
Yong Zhang ◽  
Maosong Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Clinical Outcomes ◽  
Disease Diagnosis ◽  
Advanced Lung Cancer ◽  
Insertion Mutation ◽  
Targeted Agents ◽  
First Line ◽  
Line Therapy ◽  
Exon 20

Background: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. Methods: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Results: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women ( n = 24), never smokers ( n = 32), and having the adenocarcinoma genotype ( n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. Conclusion: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti- HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population.

Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

1995 ◽  
Vol 13 (5) ◽  
pp. 1089-1095 ◽  
Author(s):  
W P Vaughan ◽  
E Kris ◽  
J Vose ◽  
P J Bierman ◽  
P Gwilt ◽  
...  
Keyword(s):  
Phase I ◽  
Continuous Infusion ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

Treatment Results With Dasatinib Or Nilotinib In Third Line Therapy Of Chronic Myeloid Leukemia After Failure Of Two Tyrosine Kinase Inhibitors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5189-5189
Author(s):  
Beatriz F Ribeiro ◽  
Eliana C M Miranda ◽  
Marcia T Delamain ◽  
Gislaine Borba Oliveira ◽  
Maria Helena Almeida ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Cytogenetic Response ◽  
Molecular Responses ◽  
The Third ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Tki Discontinuation

Abstract Chronic myeloid leukemia (CML) patients with imatinib failure are usually treated with second generation tyrosine kinase inhibitors (TKI). In case of dasatinib or nilotinib intolerance or resistance patients with HLA matched donor are submitted to allogeneic hematopoietic stem cell transplantation (HSCT) or switch treatment to a different TKI. Aims to evaluate complete hematological response (CHR), cytogenetic and molecular responses, overall, progression free and event free survival (OS, FPS and EFS) in CML patients in third line therapy that previously used 2 TKI. BCR-ABL mutations was also evaluated in this population Patients and methods between July 2008 and August 2012 26 CML patients were evaluated: 10 patients (pts) treated with dasatinib (38,5%) and 16 with nilotinib (61,5%) in third line therapy. OS, PFS and EFS were calculated with Kaplan-Meier method and Log-Rank was used for comparison, from the date of the third TKI start. The events for PFS were progression to accelerated phase (AP) or blast crisis (BC) and death. For EFS, were considered loss of CHR, loss of complete cytogenetic response (CCR), TKI discontinuation for failure or intolerance, progression or death. Patients were censored in HSCT date or TKI discontinuation for cytogenetic and molecular responses evaluation, but not for OS. Mutational analysis was done with Sanger sequencing. Results 13 male (50%) and 13 female patients with median age 54 years (22-75) and median follow-up of 32 months were analyzed (1-59). Previous response to imatinib: only one patient has achieved CCR. Status before third TKI start: 19 (73%) less than partial cytogenetic response (PCyR); 2 (7,7%) PCyR; 4 (15,5%) CCR;and 1 (3,8%) clonal evolution. 8/18 (42%) patients presented the following mutations: F317L (2), E255V (1), Y253H (1), M351T (1), M244V (1) e F359V (2). The median time of the third TKI treatment was 171 days (15-1140). Responses to third line TKI: CHR 17/19 (89%) in CP; 3/3 AF; 0/4 BC; CCR: 3/19 in CP (2 pts at 3 months and one in the 12º month); 1/3 AP; 0/4 BC; MMR: 4/19 in CP; 1/3 AP; 0/4 in BC. Nine lost CHR (45%) (8 in CP and one in AP). At 3 months, 1/21 pts (4.5%) achieved MMR; 2/13 (15%) at 6 months, while at 12 months 1/11 (9%) had MMR. At 3 months 11/21 had a BCR-ABL/ABL(IS) >10% and at 6 months 10/13 >1%. Three patients progressed to advanced phases (11,5%) ; 6 (23%) died (4 due to LMC, 1 acute myocardial infarction and 1 from graft vs host disease after HSCT; one lost follow-up. Third line treatment was discontinued in 12 (46%) pts: 6 for resistance, 2 death; 2 intolerance and resistance; 1 intolerance and one loss of follow-up. OS, PFS and EFS were 69%, 68% e 30% respectively(figure 1). OS was inferior in AP and BC in comparison with CP (0% vs 50% vs 90% - p< 0,0001)(figure 2). In summary responses may be obtained with dasatinib or nilotinib after 2 TKI failure, but they are not durable in advanced phases. Besides the results, that is an alternative for disease stabilization until the identification of a suitable donor or for patients with no performance status for HSCT. Disclosures: No relevant conflicts of interest to declare.

Hand–foot syndrome (HFS) as a potential biomarker of efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 320-320 ◽  
Author(s):  
M. D. Michaelson ◽  
D. P. Cohen ◽  
S. Li ◽  
R. J. Motzer ◽  
B. Escudier ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Time Dependent ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Independent Predictor ◽  
Potential Biomarker

320 Background: HFS and related skin toxicities are common side effects of tyrosine kinase inhibitors such as SU, a multitargeted inhibitor of VEGF and PDGF receptors plus other receptor tyrosine kinases. In a randomized phase III trial of treatment-naïve mRCC pts, SU showed superior progression-free survival (PFS) and objective response rate (ORR) over interferon-alfa, with a median PFS of 11 mo and median overall survival (OS) of 26.4 mo, establishing SU as a reference standard of care (Motzer et al, 2009). In this retrospective analysis, correlations between SU-associated HFS and efficacy endpoints were investigated in mRCC pts from 5 clinical trials in the first- and second-line treatment settings. Methods: Analyses included pooled data from 770 pts who received single-agent SU as 50 mg/d on a 4-week-on/2-week-off schedule (n=544; 71%) or 37.5 mg continuous once-daily dosing (n=226; 29%). Median PFS and OS were estimated by Kaplan–Meier methods and compared between pts with vs without HFS using a log-rank test. ORR was compared by Pearson's chi-square test. Tumor response was assessed by investigators and adverse events were recorded regularly. Multivariate and time-dependent covariate analyses were performed. Results: Of 770 pts, 179 (23%) developed any-grade HFS, compared with 591 (77%) who did not. Most instances of HFS (63%) initially occurred during the first 3 treatment cycles. Pts who developed HFS had significantly better ORR (55.6% vs. 32.7%), PFS (14.3 vs. 8.3 mo), and OS (38.3 vs. 18.9 mo) than pts who did not develop HFS (p<0.0001). In a multivariate analysis, SU-associated HFS remained a significant independent predictor of both PFS and OS (and of OS by time-dependent covariate analysis). Conclusions: In mRCC pts, SU-associated HFS was significantly and independently associated with improved clinical outcomes. Overall, pts who did not develop HFS still had substantial benefit from SU. However, the presence of HFS identified a subset of pts that manifested highly favorable efficacy results with SU. These findings suggest that development of HFS may serve as a predictive biomarker of SU efficacy, although prospective validation is warranted. [Table: see text]

Down-regulation of KRAS-interacting miRNA-143 to predict prognosis and response to EGFR-targeted agents in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Florian Eisner ◽  
Michael Stotz ◽  
Hellmut Samonigg ◽  
Sigurd Lax ◽  
Gerald Hoefler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Wild Type ◽  
Down Regulation ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Expression Levels

e14066 Background: MicroRNA-143 is frequently down-regulated in colorectal cancer (CRC) and influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of microRNA-143. However, the prognostic significance of microRNA-143 expression and the ability to predict the patient response to EGFR-targeted agents have not been explored yet. Methods: In this study, we analyzed 77 CRC harboring wild-type KRAS and obtaining treatment with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured by RT-PCR in both CRC and corresponding non-neoplastic colon tissue and the expression levels were correlated with clinico-pathological characteristics. Cancer-specific survival was calculated by uni- and multivariate analyses. The progression-free survival and objective response rates on EGFR-targeted therapy were also evaluated. Results: Down-regulation of microRNA-143 was observed in 47/77 (61%) CRC. Multivariate Cox regression analysis identified low levels of microRNA-143 expression as an independent prognostic factor with respect to cancer-specific survival (HR=1.92, CI=1.1-3.4, p=0.024). A significant difference was observed with respect to progression-free survival on EGFR-targeted therapy (p=0.031, log-rank test), but there were no significant differences with regard to the objective response rate. Conclusions: Our data suggest that microRNA-143 expression levels serve as independent prognostic biomarker for KRAS wild-type CRC patients but not as predictor for EGFR-targeted therapy. In addition, we consider microRNA-143 as a potential drug target for future therapy of CRC.

Targeted agent use in patients with cancer at the end of life.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 215-215 ◽  
Author(s):  
David Hui ◽  
Meghan Sri Karuturi ◽  
Kimberson Cochien Tanco ◽  
Jung Hye Kwon ◽  
Sun Hyun Kim ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
End Of Life ◽  
Hematologic Malignancies ◽  
Poor Quality ◽  
Chemotherapeutic Agents ◽  
Concurrent Chemotherapy ◽  
Targeted Agents ◽  
Patients With Cancer ◽  
Lung Malignancies ◽  
Targeted Agent

215 Background: Chemotherapy use at the end of life is considered an indicator of poor quality of care. The use of targeted agent has not been well characterized. In this study, we determined the frequency and predictors of targeted therapy use in the last 30 days of life. Methods: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had contact with our institution within the last three months of life were included. We collected baseline demographics and data on chemotherapy and targeted agents. Results: 816 patients were included: average age 62 (range 21 to 97), female 48% and White 61%. The median interval between the last treatment and death was 47 (interquartile range 21 to 97) days for targeted agents and 57 (26 to 118) days for chemotherapeutic agents. 116 (14%) patients received targeted agents and 147 (18%) received chemotherapy within the last 30 days of life. 43 (5%) patients received targeted agents had concurrent chemotherapy. The most common targeted agents in the last 30 days of life were erlotinib (n=25), bevacizumab (n=20) and rituximab (n=11). In multivariate analysis, younger age, hematologic, and lung malignancies were associated with increased targeted agent use in the last 30 days of life (Table). Conclusions: Targeted agents were used as often as chemotherapy at the end of life, particularly among younger patients and those with hematologic malignancies. Guidelines on targeted therapy use at the end of life are needed. [Table: see text]

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