Retrast: Retreatment after adjuvant trastuzumab—Our regional southern Italy experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11526-e11526
Author(s):  
Michele Caruso ◽  
Vincenzo Adamo ◽  
Paolo Tralongo ◽  
Dario Giuffrida ◽  
Vittorio Gebbia ◽  
...  
Keyword(s):  
Median Time ◽  
Early Stage ◽  
Rare Event ◽  
Standard Of Care ◽  
First Line ◽  
Primary Resistance ◽  
Adjuvant Trastuzumab ◽  
First Line Therapy ◽  
Line Of Therapy ◽  
Metastatic Sites

e11526 Background: Trastuzumab (T) is the standard of care for pts with HER2+ve BC. Relapse after adj T remains a rare event. Since the large use of T in adj setting, becomes crucial to evaluate advantages of retreatment with T for pts who relapsed after treatment in early stage. There is still lack of clinical evidence and poor data from CT to say that there is a benefit in T re-exposure after relapse following adj T. Methods: Since Jun 2006 and Dec 2011, we reviewed pts with early BC treated with T in adj therapy, relapsed and re-treated with T in first line therapy, in 10 departments of medical oncology in Sicily. We aimed to study feasibility, responses and treatment outcome. Results: 62 pts with HER2+ve fulfilled the criteria for this analysis and 47 were evaluated. Pts had a median age of 53 ys (29-79). ER/PgR-ve cases were 16 (34 %). Ki67 was > 20% in 34 pts (74%). 31 pts (64%) had >3 nodes+ve. All the pts received adj therapy with anthra+/-taxane. 55% of pts had >2 metastatic sites. 12 (25,5%) pts were revalued for HER2: 10 pts confirmed 3+ and two pts 2+ were FISH+. Median time from diagnosis to relapse was 25 mos (7 – 36). Median time from last dose of T to relapse was 10 ms (2 – 35). 33 (70,2%) pts and 14 pts (29,8%) had early (< 12 ms) and late progression (≥ 12 ms) respectively after adj T. First line of therapy was T in combination with mono/polychemotherapy in 42 pts (89,3%) and 5 pts (10,6%) respectively. 27 pts (57,4%) had objective responses (CR 5, PR 22) and 7 pts (14,8%) stable disease. 13 pts (27,6%) had progression: all of these pts had early progressive disease after adj T, 9 pts (69,2%) had Ki67>20%, 5 pts (38,4%) were ER/PgR-ve and 8 pts (61,5%) ER/PgR+ve. Median TTP was 4 mos (range 2-7). Median TTP for early and late relapses pts were respectively 3,7 and 4,8 mos, (p = 0,4). Median OS from relapse to death was 23 mos (r 12 – 37). LVSD G1 (EF < 60-50%) was observed only in 7 pts (14%). Conclusions: Our data confirm the feasibility and safety of treatment with T after adj T therapy and is active for a disease control rate in 72,4% of cases. These results demonstrate that relapses after adj T occurred early (<12 ms) in 70% of pts. However pts with primary resistance (27,6%) should be well categorized using biomolecular markers to receive up-front drugs that overcome the resistance to T.

Presentation and treatment of HER2-positive metastatic breast cancer patients already treated with adjuvant trastuzumab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 619-619
Author(s):  
Davis Yuri Torrejon ◽  
Serena Di Cosimo ◽  
Gessami Sanchez-Olle ◽  
Judith Balmaña ◽  
Meritxell Bellet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Median Time ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
First Line ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

619 Background: The introduction of trastuzumab in the clinical armamentarium has profoundly changed the natural history of HER2 positive breast cancer (BC). However, about 15% of patients with HER2 early BC treated with adjuvant trastuzumab continue to relapse. We aimed to analyze these patients with respect to clinical presentation and response to treatment. Methods: Data were retrieved from the institutional BC database of Vall d’Hebron. All the cases relapsing after exposure to adjuvant trastuzumab were analyzed. Change in expression of hormone-receptor (HR) and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis was also evaluated Results: A total of 270 patients were identified. Twenty-six patients (9.6%) relapsed (Table). Overall median time from diagnosis to relapse was 27.1 months (24.1-30.1) being 29.1 months (14.3-44.1) in HR positive and 23.1 (9.9-36.2) in HR negative cases (p=0.037). Median time from last dose of trastuzumab to relapse was 7.6 (2.7-12.7) months, being 10.6 (0-27.9) and 3 months (0-7.6) in HR positive and negative cases, respectively (p=0.026). Sixteen patients have already progressed to first-line therapy with a median time to progression (TTP) of 7.4 months with no statistical difference among HR positive and HR negative (4.4 and 9.8 months, p=0.3). No difference was found in TTP to first line therapy among early (before 12 months) and delayed (after 12 months) progression on adjuvant trastuzumab. Among the 17 cases with primary tumor and matched metastatic biopsy, HER-2 negativization was detected in 2 cases; whereas a change in estrogen and progesterone receptors was seen in 17.6% and 29.4% of cases, respectively. Conclusions: Patients with HER2+/HR negative treated with adjuvant trastuzumab seems to have a significantly shorter time to relapse compared with the HER2+/HR+ tumors. In these patients biopsy of metastatic lesions might help to define the best treatment options. [Table: see text]

Updated phase II study results of capecitabine (X) + irinotecan (I) + bevacizumab (A) as first-line therapy for metastatic colorectal cancer (MCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15064-e15064
Author(s):  
S. Beslija ◽  
M. Banjin ◽  
S. Jungic ◽  
N. Obralic ◽  
G. Kecman-Malcic ◽  
...  
Keyword(s):  
Phase Ii ◽  
Early Stage ◽  
Progression Free Survival ◽  
Disease Stage ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Highly Active ◽  
Study Results ◽  
Metastatic Sites

e15064 Background: The oral fluoropyrimidine X has improved efficacy, safety, and convenience vs. 5-FU/LV in MCRC [Van Cutsem et al. Br J Cancer 2004] and early-stage colon cancer [Twelves et al. NEJM 2005]. A recent study showed that I + X q2w is active and well tolerated [Garcia-Alfonso et al. ESMO 2006]. The humanized monoclonal antibody A targets VEGF and limits tumor angiogenesis. The addition of A to 5-FU/LV/I (IFL regimen) improves survival significantly in patients (pts) with MCRC [Hurwitz et al. NEJM 2004]. Replacing 5-FU/LV with X in this combination is a logical step forward. Here we report data from an open-label phase II trial of XIA in MCRC. Methods: Pts with untreated, histologically confirmed MCRC received I 175mg/m2 i.v. d1, X 1,000 mg/m2 orally bid d2–8, and A 5 mg/m2 d1. Treatment was repeated q2w x 12 cycles in the absence of progressive disease (PD) or unacceptable toxicity. Pts without PD after 12 cycles of XIA continued on the same dose of A + X 1,500 mg/m2 bid d2–8, q2w. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rate (ORR, RECIST), overall survival (OS), safety, and quality of life. Results: 57 pts have been enrolled. Baseline characteristics: M/F 44%/56%; median age 52 years (range 30–70); disease stage at initial diagnosis II/III/IV 16%/9%/75%; no. of metastatic sites 1/>1 47%/53%; most common metastatic site liver. Pts received a median 12 cycles (range 1–12) of XIA. All 57 pts are evaluable for safety and 56 for efficacy. ORR is 46% (3 CR, 13 PR); 5 pts (22%) have stable disease and 35 have PD. Median PFS and OS are 14.9 months (range 1.7–39.2) and 18.3 months (range 2.9–39.2), respectively. Grade 3 adverse events occurring in more than 1 pt are diarrhea (9%), hypertension (9%), hand-foot syndrome (7%), ileus (4%), and hypertriglyceridemia (4%); there is one report of grade 4 leucopenia. Conclusions: The XIA combination appears to be highly active and well tolerated as first-line treatment for MCRC; further studies of XIA are warranted. [Table: see text]

scholarly journals Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes

2018 ◽  
Vol 29 ◽  
pp. ix150 ◽  
Author(s):  
D. Planchard ◽  
M. Boyer ◽  
J.-S. Lee ◽  
A. Dechaphunkul ◽  
P. Cheema ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Standard Of Care ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Egfr Tki

PP126 MEA In Italy: Correlation Between Time To Payment By Result And Time To Off Treatment Curve

2017 ◽  
Vol 33 (S1) ◽  
pp. 131-132
Author(s):  
Gabriele Vittoria ◽  
Antonio Fascì ◽  
Matteo Ferrario ◽  
Giovanni Giuliani
Keyword(s):  
Clinical Trials ◽  
Treatment Failure ◽  
Median Time ◽  
Real Life ◽  
Standard Of Care ◽  
Phase Iii ◽  
Experimental Drug ◽  
The Mean ◽  
Line Of Therapy ◽  
Mean Time

INTRODUCTION:Payment by result agreements have been quite widely used in Italy to provide access for high costs oncologic drugs and minimize uncertainties of real life benefits (1). The aim of this analysis was to overview the Roche experience in terms of Payment by Result (Pbr) in oncology and investigate the relation between timing for the evaluation of treatment failures and observed Time to Off Treatment (TTOT) from Phase III clinical trials (2).METHODS:A retrospective analysis of the Roche payment by results schemes in place in Italy was conducted. For each drug included in the analysis it was collected: (i) the negotiated timing to assess the treatment failure for payment by result, (ii) the median time to off treatment curve observed in clinical trials for the experimental drug, (iii) the median time to off treatment observed in clinical trials for the control arm. The mean ratios between timing to assess the treatment failure for payment by result and the time to off treatment observed for the experimental drug or the median time to off treatment observed in the control arm were calculated to identify potential correlations. High level of correlation was expected if ratio was close to 1 (±.2).RESULTS:Roche products or different indications of the same product were identified as candidates for the analysis from 2008 to 2016. The timing for the evaluation of treatment failures for Pbr varies between 2 and 9 months, depending on the type of tumor and line of therapy. The mean Time to Payment By Result (TTPbr) / Control arm Time To Off Treatment (cTTOT) ratio was 1.16 (±.37) while the mean Time to Payment By Result (TTPbr) / Experimental arm Time To Off Treatment (eTTOT) ratio was .71 (±.13). Data analysis according to different time periods shows that the mean TTPbr/cTTOT and TTPbr/eTTOT for drugs negotiated from 2008 to 2015 were respectively 1.07 and 1.39 whereas for drugs negotiated in 2016 were respectively and .63 and 1.CONCLUSIONS:Good level of correlation between TTPbr and cTTOT was found. This finding is in line with the methodology used by Italian Medicines Agency so far, leveraging the cTTOT as the most appropriate proxy to assess any incremental effect of a new drug compared to the previous Standard of Care. The analysis over time of TTPbr shows that in the first years of payment by result negotiation TTPbr is more correlated to the cTTOT whereas in the last years is moving closer to the experimental one.

scholarly journals Left Atrial Appendage Closure Devices For Stroke Prevention

2014 ◽  
Vol 3 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Sunil Kapur ◽  
Moussa Mansour
Keyword(s):  
Left Atrial ◽  
Left Atrial Appendage ◽  
Standard Of Care ◽  
Atrial Appendage ◽  
First Line ◽  
Current Standard ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patients At Risk ◽  
Review Current

Cardioembolic stroke is a major cause of morbidity and mortality in patients with atrial fibrillation (AF). The left atrial appendage (LAA) is the prominent source of clot formation. While systemic anticoagulation is the current standard of care, anticoagulants carry many contraindications and possible complications. Techniques for elimination of the LAA are in various stages of development and early clinical use. In the coming years, accumulating data will help guide the management of AF patients at risk of bleeding as well as potentially become first-line therapy to reduce the risk of thromboembolic stroke. The purpose of this article is to review current endovascular and epicardial catheter-based LAA occlusion devices and the clinical data supporting their use.

Standard of Care in First-Line Therapy of DLBCL

2018 ◽  
pp. 145-155
Author(s):  
Greg Nowakowski ◽  
Fabian Frontzek ◽  
Norbert Schmitz
Keyword(s):  
Standard Of Care ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

RIT with 90Y Ibritumomab Tiuxetan in Patients with Non-Hodgkin Lymphoma Over 65 Years.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2742-2742
Author(s):  
Marcio M Andrade ◽  
Anel Montes ◽  
Ilda Murillo ◽  
Jose M Grasa ◽  
Teresa Baringo ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Median Time ◽  
Response Rate ◽  
Haematological Toxicity ◽  
Red Blood Cell Transfusion ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin Lymphoma ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 2742 Introduction: 90Y Ibritumomab tiuxetan (90Y-IT) has become an efficient alternative to therapy in non-Hodgkin Lymphoma, mainly in elderly patients. The aim of this study is to analyse our updated information of patients treated with 90YIbritumomab/tiuxetan in a prospective study according clinical practice setting and to analyse treatment outcome. Subjects and Methods: 39 non Hodgkin lymphoma patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. According the inclusion criteria: patients over 65 years old diagnosed as CD20+ NHL with neutrophils ≥ 1,5 × 109/L, platelets ≥ 100 × 109/L, bone marrow lymphocytes CD20+ ≤ 25%. All patients received 0,3 or 0,4 mCi /kg IV (88%) of 90YIbritumomab/tiuxetan and response evaluation was performed 12 weeks after. Period of study: September 2005/July 2012. The 90Y-IT was administered as consolidation of first line therapy (Rituximab alone, R-COP, R-CHOP21) or in relapsed/refractory status. Endpoints: Objective response rate (ORR), time to relapse (PFS) overall survival (OS) and safety. Other clinical prognostic factors were observed to assess their possible influence upon treatment value. Results: Until May 2012, 39 patients had received treatment with 90YIbritumomab/tiuxetan and completed the evaluation protocol and were considered to analysis; M/F 18/21 mean age 72.8 years (65–87); ECOG 0–1 92.3%. According OMS classification: NHL-follicular 27 (69.2%), mantle cell Lymphoma 7 (17.9%), DLBCL 4 (10.3%) and 1MALT (2.6%). Score distribution: low risk 19 (48.7%), intermediate 12 (30.8.2%) and advanced 8 (20.5%). Previous therapy schedules ≤2 (66.7%), >2 (33.3%). The median follow-up time: 42.0 months (95% CI: 4.0; 62.0), mean PFS: 38.1 months (95% CI: 30.8; 45.4) median NR. 13 patients received 90Y-IT as consolidation of first line therapy (33.3%) and 26 relapsed/refractory (66.6%). ORR was 84.6 % CR: 29 (74.3%); PR 4 (10.2%) and 6 failures (15.4%) in relapsed/refractory disease. Mean estimated OS since 90Y-IT: 54.4 months (95% CI: 49.4; 59.3) and mean estimated OS since diagnosis 159 months. Median PFS was NR. The mean PFS for patients in consolidation therapy was 54.2 months (95% CI: 47.4; 61.1). Safety: thrombocytopenia being the most frequent, G3–4 (35.9%), median time to developed haematological toxicity: fourth week, and neutropenia G3–4 (41.0%), the median time to recover normal values was 4.2 and 2.6 weeks respectively. In 5 (12.9%) of patients red blood cell transfusion was required, and 10 platelet transfusions (25.6%). The most frequent non haematological toxicity was asthenia. One patient developed a severe mucositis. Four patients have concomitant associated tumours (colon, breast, lung and prostate) and two patients over 77 years developed a rectum carcinoma after 18 months of 90Y-IT and another prostate and renal tumour after 8 years. Comments: In our experience 90Y Ibritumomab tiuxetan is a safety and effective therapy in patients with NHL over 65 years. According to obtained PFS results, it seems like the use of this kind of therapy as used in early part of therapy offers good and maintained response rate with lower toxicity in this fragile population. The OS in this population was not inferior to observed in younger NHL patients. Disclosures: No relevant conflicts of interest to declare.

Randomized trial of sequence vs. combination of capecitabine (X) and docetaxel (T): XT vs. T followed by X after progression as first-line therapy for patients (pts) with metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
S. Beslija ◽  
N. Obralic ◽  
H. Basic ◽  
A. Tatarevic ◽  
M. Naila ◽  
...  
Keyword(s):  
Metastatic Breast ◽  
Treatment Rate ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Weekly Cycles

571 Background: Capecitabine (Xeloda [X]) and docetaxel (Taxotere [T]) are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-preatreated MBC [O’Shaughnessy et al. J Clin Oncol 2002], although only one third of pts in the T group received X after progression. We designed this study to determine whether XT is better than sequential T→X in first-line MBC. Methods: 100 pts with measurable MBC, prior adjuvant anthracyclines (100%) but no prior chemotherapy for MBC and KPS ≥70 received 3-weekly cycles of either XT (X 1250mg/m2 bid d1–14 + T 75mg/m2 d1) or T→X (T 100mg/m2 d1 followed after progression by X 1250mg/m2 bid d1–14). X monotherapy data were not considered in the RR or TTP analyses but were included for OS and safety. Results: The XT and T→X arms were well balanced for prognostic factors: median age 48 (29–59) vs. 51 (31–64) years; median KPS 100 (70–100) in both arms; hormone-responsive disease 20 vs. 16%; dominant metastatic sites (liver 42 vs. 44%, lymph nodes 34 vs. 36%, lung 28 vs 24%, bone 20 vs 18%); number of involved organs (1 = 58 vs. 52%, >1 = 42 vs. 48%); median interval since prior adjuvant anthracyclines (18.5 vs. 17.0 months). Efficacy findings are shown in the table . 74% of the pts in the T→X arm crossed-over to X on progression. The post-study treatment rate was similar in both arms. The most common grade 3/4 adverse events (>5% of pts) with XT vs. T→X were: hand-foot syndrome 18 vs. 4%; stomatitis 16 vs. 8%; neutropenia 12 vs. 14%; neutropenic fever 12 vs. 14%; diarrhea 12 vs. 8%; fatigue 8 vs. 12%; alopecia 6 vs. 8%; edema 4 vs. 8%. Dose reductions were necessary for 52% of pts on XT and 36% of pts on T→X. Conclusions: XT provides significant RR, TTP and OS advantages over T→X. XT should be the standard therapy in fit poor-prognosis pts with aggressive disease. [Table: see text] No significant financial relationships to disclose.

Preliminary phase II study results of capecitabine (X) + irinotecan (I) + bevacizumab (A) as first-line therapy for patients (pts) with metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14502-14502
Author(s):  
S. Beslija ◽  
M. Banjin ◽  
S. Jungic ◽  
N. Obralic ◽  
G. Kecman-Malcic ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Early Stage ◽  
Progression Free Survival ◽  
Disease Stage ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Study Results

14502 Background: The oral fluoropyrimidine X (Xeloda®) has improved efficacy, safety and convenience compared with 5-FU/LV in MCRC [Van Cutsem et al. Br J Cancer 2004] and early-stage colon cancer [Twelves et al. NEJM 2005]. A recent study showed that I + X q2w is active and well tolerated [Garcia-Alfonso et al. ESMO 2006]. The humanized monoclonal antibody A (Avastin®) targets VEGF and limits tumor angiogenesis. The addition of A to 5-FU/LV/I (IFL regimen) results in significant improvements in survival among pts with MCRC [Hurwitz et al. NEJM 2004]. Replacing 5-FU/LV with X in this combination is a logical step forward. Here we report data from an open-label phase II trial of XIA in MCRC. Methods: Pts with untreated, histologically confirmed MCRC received I 175 mg/m2 i.v. d1, X 1000 mg/m2 orally bid d2–8, and A 5 mg/m2 d1. Treatment was repeated q2w x12 cycles in the absence of disease progression or unacceptable toxicity. Pts without progressive disease after 12 cycles of XIA continued on the same dose of A + X 1500 mg/m2 bid d2–8, q2w. The primary endpoint was progression-free survival (PFS); secondary endpoints were response rate (RECIST), overall survival (OS), safety, and quality of life. Results: 24 out of a planned total of 32 pts have been enrolled. Baseline characteristics are: M/F 50%/50%; median age 53 years (range 30–70); disease stage at initial diagnosis IIIA/IIIB/IV 29%/21%/50%; no. of metastatic sites 1/>1 50%/50%; most common metastatic site liver; prior adjuvant therapy 33% (Mayo 5-FU/LV). Pts received a median of 12 cycles (range 1–18) of XIA. All 24 pts are evaluable for safety and 22 for efficacy. The overall response rate is 77% (4 CR, 13 PR); 2 pts (9%) have stable disease and 3 have progressed. One pt has died. Median PFS and median OS have not yet been reached. The only grade 3 adverse events are diarrhea (13%), fatigue (4%), mucositis (4%), enteritis (4%), ileus (4%); there is one report of grade 4 leucopenia. All other adverse events are mild-to-moderate. Conclusions: The XIA combination appears to be highly active and well tolerated as first-line treatment for MCRC, providing support for further evaluation of this combination. No significant financial relationships to disclose.

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