Early experiences with triple immunochemotherapy in young adults with high-risk fibrolamellar carcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Claire O'Grady ◽  
Ariel Gliksberg ◽  
Paul Kent
Keyword(s):  
Young Adults ◽  
High Risk ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Good Tolerability ◽  
Interferon Alpha 2B ◽  
Early Results ◽  
Systemic Treatments ◽  
Fibrolamellar Carcinoma

510 Background: Fibrolamellar Carcinoma (FLC) is a rare liver cancer affecting young adults without underlying liver disease. Surgery is the only proven therapy, and recurrence is common. There are no proven systemic treatments, especially for high-risk FLC (unresectable, relapse, progression, metastatic). Research suggests that immunotherapy may work. We share our experience using systemic “triple immunochemotherapy” (TT): 2 week cycles of 7 days continuous infusion 5FU or oral capecitabine, interferon alpha-2b on days 1,3,5,7 or PEG-Interferon and nivolumab on day 1. Methods: Data from all patients who received TT from 5/2018 to 9/2019 was reviewed to assess tolerability, survival and toxicity. Results: 14 patients were treated with TT of which 10 (8F,2M with a median age of 20) were evaluable. They received a median of 13 cycles (6-31). At time of analysis, the median progression free survival was 6 months, 22% longer than prior to TT, with 80% of patients (8) stable or improving, 1 progression, and 1 who died 2 months after initiating TT. For the 4 patients who achieved surgical remission, none have relapsed (PFS 9 months). Overall objective response (CR+PR) and tumor control rate (CR+PR+SD) were 60% and 80%, respectively. There were no withdrawals from treatment due to side effects, though 2 had dose adjustments. All experienced mild adverse effects, most commonly fever and headache, but only 2 patients had grade 3 toxicity. Conclusions: Our early results of TT for high-risk FLC are promising, with good tolerability and treatment response, particularly in patients who have achieved surgical CR. Further longitudinal data is needed to confirm outcomes, especially in patients still early in their treatment. [Table: see text]

Early Experiences with Triple Immunochemotherapy in Adolescents and Young Adults with High-Risk Fibrolamellar Carcinoma

Oncology ◽  
2021 ◽  
Vol 99 (5) ◽  
pp. 310-317
Author(s):  
Sara Gottlieb ◽  
Claire O’Grady ◽  
Ariel Gliksberg ◽  
Paul Kent
Keyword(s):  
High Risk ◽  
Partial Response ◽  
Clinical Remission ◽  
Objective Response ◽  
Progression Free Survival ◽  
Outpatient Setting ◽  
Tumor Control ◽  
Good Tolerability ◽  
Early Results ◽  
Fibrolamellar Carcinoma

Introduction: There are no standard systemic therapies for the treatment of fibrolamellar carcinoma (FLC), as surgery remains the only definitive option. We share our experiences using systemic “triple therapy” (TT) with 5-fluorouracil, interferon, and nivolumab for the treatment of relapsed, refractory, metastatic, or unresectable FLC. Methods: Data from all patients who received TT from May 2018 to July 2020 were reviewed to assess response, survival, and toxicity. Results: A total of 22 patients were treated with TT, of which 14 (median age of 21 years) were evaluable. They received a median of 18 cycles (8–44). At the time of analysis, the median progression-free survival was 9 months (4.5–26), 29% longer than prior to TT, with 5 patients achieving clinical remission, 8 patients stable or improving, and 1 progression. Overall objective response (clinical remission + partial response) was 50% and tumor control rate (clinical remission + partial response + stable disease) was 93%. Two patients withdrew from treatment due to side effects. Discussion/Conclusion: Our early results support TT as a promising medical option to slow disease progression and prolong survival in high-risk patients with FLC. TT can be administered in the outpatient setting and has shown good tolerability. Further longitudinal data is needed to confirm outcomes, especially in patients still early in their treatment.

Novel systemic therapies in hard to treat fibrolamellar hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16653-e16653
Author(s):  
Ariel Gliksberg ◽  
Claire O'Grady ◽  
Paul Kent
Keyword(s):  
High Risk ◽  
Metastatic Disease ◽  
Objective Response ◽  
Tumor Control ◽  
Primary Therapy ◽  
Early Results ◽  
Systemic Treatments ◽  
Multi Agent ◽  
Grade 3 ◽  
Systemic Therapies

e16653 Background: Fibrolamellar Carcinoma (FLC) is a very rare liver malignancy of young adults without underlying liver disease (0.02 per 100,000 in the US).. Complete resection is the primary therapy, but recurrence rates are still > 50%. Currently there are no established systemic treatments, especially for high-risk disease (unresectable, relapse, progression, or metastatic disease). At our institution triple therapy “TT” with Nivolumab/5FU/Interferon α-2b is our first line, followed by other novel combination therapies such as Gemcitabine/Oxaliplatin/Lenvantinib (GOL) or Nivolumb/Lenvantinib/Quecertin (NLQ). Objective: To evaluate the tolerability and early response of multi-agent systemic therapies in patients with high-risk FLC. Methods: Data from all patients with FLC who received systemic therapies from 5/2018 to 2/2020 was reviewed to assess tolerability, survival and toxicity. Results: Nineteen patients were treated with systemic therapies of which 16 (10F, 6M median age of 19) were evaluable based on follow up scans. Between our 16 patients they had relapsed 28 times, 12 had metastatic disease and 7 had tried 2+ systemic therapies. RECIST 1.1 objective response (CR+PR) and tumor control (CR+PR+SD) are 44% and 69%. Since starting multi-agent therapy, all 6 patients who had previously been treated with monotherapy, have already exceeded their previous longest time to progression. Thirteen patients were treated with “TT” [12.5 median cycles (6-38)]. Three patients were treated with NLQ including 2 who failed TT. Of these, the 1 evaluable patient achieved CR. Two patients were treated with GOL, 1 who failed TT and one who was post liver transplant, both had sustained PR of 6 and 9 months. Subsequently one died and one achieved CR. For the 6 patients who achieved remission before or during therapy, only 1 has relapsed. To date the period of response is already 68% longer than the previous best length of response. There was 1 withdrawal due to grade 3 colitis and 2 dose adjustments. All experienced mild adverse effects, most commonly fever, headache, and hypertension, with 3 patients with grade 3 toxicities. Conclusions: FLC is a devastating disease with patients often relapsing even after successful surgical remission. Currently there is a need for tolerable systemic therapies. Although at our institution, TT is our frontline therapy, there are other combinations of immunochemotherapies that we have used to treat FLC with preliminary success and minimal toxicities. Our early results show that multi-agent systemic therapy in hard-to-treat FLC is worthy of further study.

Novel systemic therapies in the treatment of fibrolamellar carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16161-e16161
Author(s):  
Sara Gottlieb ◽  
Ariel Gliksberg ◽  
Erik Schadde ◽  
Paul Kent
Keyword(s):  
Partial Response ◽  
Systemic Therapy ◽  
Clinical Remission ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Tumor Control ◽  
Multi Agent ◽  
Fibrolamellar Carcinoma ◽  
Systemic Therapies

e16161 Background: Fibrolamellar carcinoma (FLC) is an exceedingly rare liver cancer affecting children and young adults without underlying liver disease. Complete surgical resection is the primary treatment option, but recurrence is common. There are currently no established systemic therapies. We have treated patients in both the neoadjuvant and adjuvant setting with three novel combination therapies: 5-fluorouracil/interferon/nivolumab (“Triple Therapy” or TT), gemcitabine/oxaliplatin/lenvatinib (GOL), and nivolumab/lenvatinib/quercetin (NLQ). The purpose of this study was to evaluate objective responses and tolerability of three multi-agent systemic therapies in the treatment of FLC. Methods: Data from all patients with FLC who received TT, GOL, or NLQ between May 2018 and February 2021 were reviewed. Patients who received a minimum of six cycles of systemic therapy with follow up scans at least two months after initiation were assessed based on objective response, survival, and toxicity. Results: Twenty-nine patients with FLC who were treated with novel multi-agent systemic therapy were evaluable based on the above criteria. Median age at start of treatment was 20 (7-52; 16F, 12M, 1 non-disclosed). Twenty-three patients received one combination therapy (13 TT, 8 GOL, 2 NLQ), five received two different lines (3 TT/NLQ, 2 TT/GOL), and one patient received all three novel combinations. Between our 29 patients, they had relapsed 36 total times, and 11 had already tried 2+ systemic therapies. Best RECIST 1.1 objective response (clinical remission + partial response) and tumor control rate (clinical remission + partial response + stable disease) were 58%/95%, 55%/100%, and 33%/83% for TT, GOL, and NLQ respectively. The median longest Progression Free Survival (PFS) on any novel multi-agent regimen was 9 months (2-29; 9.5 for TT, 7 for GOL, 6.5 for NLQ), with 18 patients still receiving the therapy extending their PFS. Of those with previous relapses, 56% have a PFS longer than their previous longest remission and 69% have a PFS longer than their previous shortest time to relapse. Half of patients with previous relapses are still receiving the treatment responsible for their longest PFS. Fever, chills, and nausea were the most common adverse effects experienced throughout all three regimens. Seven patients experienced 1+ grade 3 adverse event. There were no toxic deaths or organ failure. Two patients died as a result of disease; their longest PFS (1 on GOL, 1 on TT) were nine and 10 months. Conclusions: FLC is a devastating cancer with patients often relapsing even after successful surgical remission. There is a strong need for effective and tolerable systemic therapies for those with unresectable, relapsed, progressive, or metastatic disease. We have had promising results in treating FLC and prolonging survival with minimal toxicities using novel multi-agent regimens.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours

2021 ◽  
Author(s):  
Ophelie De Rycke ◽  
Thomas Walter ◽  
Marine Perrier ◽  
Olivia Hentic ◽  
Catherine Lombard-Bohas ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Mgmt Expression ◽  
Pancreatic Neuroendocrine Tumours

A rechallenge is common after initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET. Secondly, to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (Cohort A). Primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (Cohort B). We foud that cohort A included 62 patients (median Ki67 8%), for which ALK1 followed by pause achieved an objective response rate of 55%, and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response, and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (p=0.032) and a pause longer than 12 months (p=0.041) were associated with a longer PFS2. In the cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK, to 100 (IQR 56-180) after ALK (p=0.003). We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.

Imatinib for the treatment of aggressive fibromatosis/desmoid tumors (AF/DT) failing local treatment: updated outcome and predictive factors for progression free survival. A FNCLCC French Sarcoma Group-GETO study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10062-10062
Author(s):  
J. Fayette ◽  
A. Dufresne ◽  
N. Penel ◽  
A. Le Cesne ◽  
B. Bui Nguyen ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Aggressive Fibromatosis ◽  
Tissue Microarrays ◽  
Long Term Results ◽  
Tumor Control ◽  
Curative Surgery ◽  
Kit Mutation ◽  
Systemic Treatments

10062 Background: The optimal treatment of AF/DT failing local treatments is not defined. We report long term results and predictive factors for response to imatinib in AF/DT. Methods: Pts =18 years with advanced AF/DT from all sites in whom neither curative surgery nor radiotherapy (RT) was possible were eligible. Imatinib was given at the dose of 400mg/d (and increased to 800 mg/d if progression) during 1 year then stopped. Primary endpoint was the progression free at 3 months. A two stages Simon‘s optimal design was used with p0=10%, p1=30%, a=0.05 and 90% power (18 pts first stage, total of 35 evaluable pts). Predictive factors were investigated using tissue-microarrays (TMA) and KIT mutation analysis. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. Median age was 40 (range 20–72) with 30% males. Primary sites were extra abdominal, mesenteric, and abdominal wall in 69, 18, and 13% of pts respectively. 23% had received RT. Prior systemic treatments were: NSAID, hormonotherapy or chemotherapy (CT) in 33%, 45% and 20% of pts respectively. Median treatment duration of imatinib is 9 months (range 0.8–13.8). G4 and G3 toxicities were notified in 0 and 17 patients (42.5%) respectively: rash (4 pts), abdominal pain (3 pts), and vomiting (3 pts). 38 pts (95%) are evaluable at 3 months, with 1 (3%) CR, 3 (8%) RP, 31 (82%) SD and 3 (8%) PD. With a median follow-up of 13.8 months, 13 of the 40 pts had progressed. PFS at one year is 71% and 1 patient died (PD). 8 patients received an increased dose of imatinib upon progression under a 400mg/d dose: 3 reprogressed and 5 achieved tumor stabilization during 5+, 6+, 8+ months. PFS was correlated to weight or to previous CT, but not to gender, Gardner, age, PS, size, site. Using TMA, the expression of PDGFR β and a β catenin, E-cadherine, cyclinD1, M-CSFR, estrogen receptor β, ERK, phospho-Akt-Ser473, phospho-MEK1–2 were investigated. None of the CycD1+ tumors have progressed so far. 3 mutations of KIT exon 10 were detected in 10 patients tested. All achieved tumor control. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT. Prognostic factors were identified. [Table: see text]

Role of trabectedin (T) in the management of advanced uterine leiomyosarcoma (U-LM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10530-10530
Author(s):  
F. Grosso ◽  
R. Sanfilippo ◽  
R. L. Jones ◽  
P. Collini ◽  
C. Morosi ◽  
...  
Keyword(s):  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Median Number ◽  
Local Relapse ◽  
Tumor Control ◽  
Uterine Leiomyosarcoma ◽  
Systemic Treatments ◽  
Genetic Features ◽  
Metastatic Sites ◽  
Clinical Records

10530 Background: To explore the clinical impact of T in U-LM. T has been approved in Europe for second line treatment of advanced soft tissue sarcomas (STS). Efficacy is well established in liposarcoma and leiomyosarcoma. U-LMs display peculiar clinical and genetic features compared to other STS. These differences may be responsible for the sensitivity of this subtype to therapy, thus justifying an evaluation of the activity of T in a relatively homogeneous series of U-LM patients. Methods: From April 2000, 56 patients (pts) with advanced disease, previously exposed to a median of 3 chemotherapy lines (range 1–5), received T within an expanded access programme at two European referral institutions for sarcoma. The clinical records were reviewed focusing on response and treatment outcome. Two pts were excluded from the analysis having received only 1 course of T. Median age was 56 yrs (range 29–73), median number of metastatic sites was 2 (range 1–4), the most frequent metastatic site was lung (88%), 24 patients had a local relapse. Results: A total of 252 courses were delivered (median 3, IQR2–6) and 36% of patients received more than 5 courses of T. Fifty-two patients were evaluable for response. A partial response was observed in 11 patients and stable disease in 15, for a PR rate of 21% and a tumor control rate of 50%. The median progression-free survival was 3.6 months (CI95% 2.6–6.7), with 41% of patients free from progression at 6 months. Conclusions: These results compare favourably with other systemic treatments in advanced U-LMS and support their sensitivity to T. This should prompt further studies to prospectively evaluate the efficacy of T in U-LMS and elucidate possible biological predictive factors (e.g. DNA repair protein expression). [Table: see text]

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
Angela Di Giannatale ◽  
Kieran Mc Hugh ◽  
Nathalie Dias ◽  
Annick Devos ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase Ii ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Alkylating Agents ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Disease Stabilization ◽  
Grade 3

9517 Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.

Association of matrix metalloproteinase 2 (MMP2) baseline plasma level to objective response (OR), progression free survival (PFS), and overall survival (OS) and changes under treatment in patients treated with bevacizumab (Bev) for recurrent high-grade glioma (HGG).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2024-2024 ◽  
Author(s):  
Emeline Tabouret ◽  
Francoise Boudouresque ◽  
Jaime Callego Perez-Larraya ◽  
Maryline Barrie ◽  
Giuseppe Lombardi ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Baseline Level ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Cytotoxic Agents ◽  
Matrix Metalloproteinase 2 ◽  
Tumor Control ◽  
Multiple Time

2024 Background: Predictive marker of Bev activity is an unmet medical need. We evaluated predictive value of selected circulating prebiomarkers involved in neoangiogenesis and invasion on patient outcome in recurrent HGG treated with Bev. Methods: A set of eleven prebiomakers of interest (VEGF, VEGF-R2, bFGF, SDF1, PlGF, uPA, PAI1, MMP2, MMP7, MMP9, and adrenomedulline) were analyzed in plasma, using ELISA, at baseline from Bev initiation in a prospective cohort of 26 patients (Cohort1). Correlations were validated in a separate retrospective Bev treated cohort (Cohort2; n = 50) and then tested in a cohort of patients treated with cytotoxic agents without Bev (Cohort3; n = 34). Dosages were correlated to OR, PFS, and OS. MMP2 and MMP9 were then analyzed at multiple time points up to progression. Results: In cohort1, high MMP2 baseline level was associated with an OR rate of 83.3% for high levels versus 15.4% for low MMP2 levels (p = 0.001). In multivariate analysis, MMP2 baseline level was correlated with PFS (hazard-ratio (HR), 3.92; 95% confidence-interval (CI):1.46-10.52; p = 0.007) and OS (HR, 4.62; 95%CI 1.58-13.53; p = 0.005), as MMP9 (p = 0.016 for PFS and p = 0.025 for OS). Similar results were found in cohort2 for MMP2, (MMP2: p<0.001 for OR; p = 0.009 for PFS; p = 0.009 for OS) but not for MMP9. In cohort3, no association was found between MMP2, MMP9 and outcome. Significant changes in MMP2 and MMP9 plasma levels were observed during treatment. MMP2 increased after Bev initiation (p = 0.002), and decreased at progression (p = 0.002) while MMP9 initially decreased (p = 0.007) then increased at progression (p = 0.031). Conclusions: In patients with recurrent HGG treated with bevacizumab, but not with cytotoxic agents, high MMP2 plasma levels are associated with prolonged tumor control and survival while changes over time may reflect tumor control. MMP2 should be tested in randomized clinical trials that evaluate bevacizumab efficacy, and its biological role should be reassessed.

BMI as a risk factor for toxicities in patients with advanced soft tissue sarcoma treated with trabectedin.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22517-e22517
Author(s):  
Marianna Silletta ◽  
Grazia Armento ◽  
Giuseppe Badalamenti ◽  
Mariella spalato Ceruso ◽  
Giovanna Catania ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Normal Weight ◽  
Rank Test ◽  
Tumor Control ◽  
Log Rank Test ◽  
Status Measure

e22517 Background: Since the first steps of its clinical development, trabectedin was noticed to be extremely active against myxoid liposarcoma (MLS), whose pathogenesis seems to be associated to the presence of the t(12;16)(q13;p11) translocation, resulting in the expression of FUS-DDIT3 fusion genes. Therefore, the drug seems to induce a maturation of MLS lipoblasts, with transition of the residual spindle non-lipogenic cells into mature vacuolated lipoblasts. This effect could be prevented by the increase of leptin circulating levels in obese patients. For these reasons we designed this retrospective analysis in order to evaluate the BMI status (measure of total adipose content) as a predictors or efficacy of trabectedin in MLS patients. Methods: Patients were treated in cancer centers with trabectedin at the approved dose of 1.5 mg/m2, given as a 24-hour infusion every 3 weeks. This retrospective analysis was preformed on the basis of clinical charts or databases. For the purpose of this analysis only patient with a BMI > 18.5 were included and an the population divided into two categories: normal weight if BMI < 25, overweight > 25. An analysis of the correlation between BMI and objective response (OR) rate, tumor control (TC) rate (OR+stable disease lasting ≥3 months), progression-free survival (PFS) and overall survival (OS) was performed. Results: 62 adult patients with recurrent MLS were enrolled (M/F: 33/29; median age: 53 ys). All patients were doxorubicin-pretreated. The median BMI in the whole population was 22.5 (range: 1.85 – 29.8). No statistically significant differences were identified in terms of OR or TC. On the contrary, PFS (6.8 vs. 3.7 months; p< 0.026, log rank test) and OS (14.9 vs. 8.3 months; p< 0.0001, log rank test) were significantly prolonged in normal weighted patients vs over weighted patients. Six and 12-months Kaplan-Meier PFS estimates and survival rates at 12, 24 and 36 months were also better in those patients. Conclusions: these results seem confirm a role o adipose content as a predictor of resistance to trabectedin in MLS patients. Further studies are warranted to confirm this preliminary observation and understand the biological mechanisms of this relationship.

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