Bevacizumab (Bv) single-agent maintenance following Bv-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): Results from an exploratory analysis of the AVAiL study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19001-e19001
Author(s):  
J. Mezger ◽  
J. von Pawel ◽  
M. Reck
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Performance Status ◽  
Single Agent ◽  
Maintenance Phase ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Significant Survival ◽  
Risk Of Progression ◽  
Post Hoc

e19001 Background: The significant survival benefits observed with Bv plus chemotherapy in pivotal NSCLC trials were generated using treatment to progression. Given that little data on the use of single-agent Bv as maintenance therapy are currently available, we report here the results of an analysis focused on the maintenance phase of the AVAiL study. Methods: AVAiL, a randomized, international, placebo-controlled phase III trial, evaluated Bv plus cisplatin-gemcitabine (CG) in pts with previously untreated advanced, non-squamous NSCLC, with performance status 0/1. 1,043 pts (age 20–83) were randomized to C 80mg/m2 and G 1,250mg/m2 q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (Bv 7.5; n=345), Bv 15mg/kg q3w (Bv 15; n=351) or placebo (Pl; n=347). Bv/Pl was administered until disease progression. This retrospective analysis focused on progression-free survival (PFS) and overall survival (OS) of the 376 patients who received blinded Bv (n=174 and n=162 for Bv 7.5 and 15) or Pl monotherapy (n=41) after completing 6 cycles of CG + Bv or CG + Pl (as specified in the protocol; most patients received 6 cycles). PFS was measured from last day of last cycle of CG + Bv/Pl to disease progression or death. Results: In the overall population, Bv reduced the risk of progression or death by 25% vs Pl (PFS primary endpoint (HR=0.75 [0.64–0.87] and 0.85 [0.73–1] for Bv 7.5 and Bv 15, respectively). When analyzing the outcome of the post chemotherapy maintenance phase, the use of Bv as single agent yielded median PFS of 3.2 months (95%CI [3–5]) for Pl, 4.6 months (95%CI [4–6]) for Bv 7.5 and 4.6 months (95%CI [4–5]) for Bv 15.The OS results for this maintenance analysis are consistent with those from the overall population in which the PFS findings were not associated with an OS benefit. Conclusions: This post-hoc analysis, focused on the maintenance phase of AVAiL, suggests that Bv used as single-agent maintenance therapy appears to confer clinical benefit beyond the chemotherapy phase. This finding warrants further exploration in future studies. [Table: see text]

scholarly journals A Review of Docetaxel: Its Use in the Treatment of Gastric Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S5191
Author(s):  
Alessandro Inno ◽  
Michele Basso ◽  
Alessandra Cassano ◽  
Carlo Barone
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Phase Ii Studies ◽  
Combination Regimens

Docetaxel, a member of the taxane family, promotes cell death by binding β-tubulin and has demonstrated activity against several human malignancies, both as a single agent and in combination therapy. It has been approved in Europe and the US as front-line treatment for advanced gastric cancer in combination with cisplatin and fluorouracil (DCF regimen). This approval was based on the results of a pivotal study (V325) which demonstrated that the addition of docetaxel to the reference regimen of cisplatin and fluorouracil improves overall survival and progression-free survival with a better quality of life despite increased toxicity (mainly haematological). Modifications of DCF regimen have been successfully investigated as a means of making the treatment more tolerable and suitable also for elderly patients or patients with poor performance status. Emerging data from several phase II studies suggest that other docetaxel-based combination regimens with anthracyclines or irinotecan have interesting activity with acceptable toxicity profiles, but the true efficacy of these regimens needs to be assessed in large randomized phase III studies. Thus, the best docetaxel-containing regimen has yet to be identified. Docetaxel also represents a good candidate for combination with novel molecular target agents. In light of the high response rates observed in phase II-III studies, a docetaxel-based chemotherapy regimen might also be considered a treatment option as perioperative or adjuvant therapy in potentially curable gastric cancer and further studies with or without biological agents are eagerly awaited in this setting.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

Carfilzomib (K) in relapsed and refractory multiple myeloma (RRMM): Frailty subgroup analysis from phase III ASPIRE and ENDEAVOR.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8028-8028 ◽  
Author(s):  
Thierry Facon ◽  
Ruben Niesvizky ◽  
Katja Weisel ◽  
Sara Bringhen ◽  
P. Joy Ho ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Frailty Status ◽  
Improved Outcomes ◽  
Comorbidity Index ◽  
Post Hoc ◽  
Frailty Score

8028 Background: K-based regimens improved progression-free survival (PFS) and overall survival (OS) in RRMM patients (pts) in ASPIRE (K [27 mg/m2]-lenalidomide-dexamethasone [KRd] vs Rd) and ENDEAVOR (K [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), regardless of age. Frailty scores have been developed based on age, comorbidities, and functional status (Palumbo Blood 2015;125:2068–74; Facon Blood 2015;126:4239). We assessed post hoc pt outcomes by frailty status. Methods: PFS, OS, and safety were assessed by treatment arm and frailty score (based on age, medical history-derived Charlson Comorbidity Index, and ECOG performance status); frailty scores: 0 = fit, 1 = intermediate (int), and ≥2 = frail. Results: Pt frailty status was balanced between treatment arms in ASPIRE and ENDEAVOR. Median PFS and OS were longer with K-based regimens vs controls in ASPIRE and ENDEAVOR across frailty subgroups (Table). Rates of treatment-emergent adverse events are summarized in the Table. Conclusions: Kd56 and KRd consistently improved outcomes vs Vd and Rd, respectively, in all frailty subgroups as defined by the algorithm above. These findings support the favorable benefit-risk profile of KRd and Kd56 regardless of frailty score. Clinical trial information: NCT01080391 and NCT01568866. [Table: see text]

OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA5007-LBA5007 ◽  
Author(s):  
C. Aghajanian ◽  
N. J. Finkler ◽  
T. Rutherford ◽  
D. A. Smith ◽  
J. Yi ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Ecog Performance Status ◽  
Fallopian Tube Cancer ◽  
Phase Iii Trial ◽  
Platinum Sensitive

LBA5007 Background: BEV, a humanized anti-VEGF monoclonal antibody, has shown a progression-free survival (PFS) benefit in 2 frontline phase III trials in patients with EOC, PPC and FTC. The therapeutic impact of BEV in combination with carboplatin (C) and gemcitabine (G) followed by single agent BEV to disease progression (PD) was evaluated in this phase III trial in the platinum-sensitive recurrent setting. Methods: Patients had recurrent, platinum-sensitive EOC, PPC or FTC, 1 prior regimen, no prior BEV, ECOG performance status 0-1, measurable disease. Subjects were randomized to: Arm A: [IV C (AUC 4, Day (D) 1) + G (1,000 mg/m2 D1 and 8) + placebo (PL) D1] q21D x 6 cycles (c) → PL q21D until PD or unacceptable toxicity (tox) Arm B: [CG + BEV (15 mg/kg) D1] q21D x 6 c → BEV q21D until PD or tox primary endpoint was investigator assessed PFS (RECIST). Secondary endpoints included objective response (OR), overall survival (OS), duration of response and safety. The design provided 80% power to detect a 27% reduction in the hazard of progression or death in Arm B vs A, limiting the overall type I error of 5%. Results: OCEANS enrolled 484 patients (242 per arm) from 4/07 - 1/10, median follow up of 24 months. BEV plus CG followed by single agent BEV to PD significantly increased PFS compared to CG alone (HR=0.484, p<0.0001). OR increased by 21% (p<0.0001). OS data is immature with only 29% of patients having had an event. The safety profile was consistent with other BEV trials. Conclusions: Results show a statistically significant and clinically relevant benefit when bevacizumab is added to chemotherapy in patients with recurrent, platinum sensitive EOC, PPC, and FTC. This is the first phase III trial of an antiangiogenic to demonstrate a clinical benefit to these patients. [Table: see text]

PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2895-2902 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Filippo de Marinis ◽  
Mircea Dediu ◽  
Michael Thomas ◽  
Jean-Louis Pujol ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Continuation Maintenance

Purpose In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. Patients and Methods In all, 939 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m2 on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). Results The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Conclusion Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.

Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2870-2878 ◽  
Author(s):  
John P. Crown ◽  
Véronique Diéras ◽  
Elzbieta Staroslawska ◽  
Denise A. Yardley ◽  
Thomas Bachelot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC. Patients and Methods Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months). Results A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm. Conclusion The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.

Maintenance Therapy After Stem-Cell Transplantation for Multiple Myeloma with Bortezomib/Thalidomide Vs. Thalidomide Vs. alfa2b-Interferon: Final Results of a Phase III Pethema/GEM Randomized Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 334-334 ◽  
Author(s):  
Laura Rosiñnol ◽  
Albert Oriol ◽  
Ana Isabel Teruel ◽  
Dolores Hernández ◽  
Javier Lopez-Jimenez ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Discontinuation Rate ◽  
End Points ◽  
Contract Research Organization ◽  
The Poor

Abstract Abstract 334 Introduction: The Spanish Myeloma Group (PETHEMA/GEM) conducted a randomized phase III trial comparing induction with thalidomide/dexamethasone (TD) vs. bortezomib/thalidomide/dexamethasone (VTD) vs. VBMCP/VBAD/Bortezomib (VBMCP/VBAD/B) in patients 65 years-old or younger with newly diagnosed symptomatic MM and ASCT with MEL-200 followed by maintenance with thalidomide/bortezomib (TV) vs. thalidomide (T) vs. alfa-2b-interferon (alfa2-IFN). The induction part of the study has been recently published and the maintenance results are reported here. End-points: The primary end-point was progression-free survival (PFS) and the secondary end-points were increase of response rate, overall survival (OS) and safety. Patients and Methods: The maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (single agent thalidomide at a dose of 100 mg daily) versus alfa2-IFN (subcutaneous alfa2b-IFN at a dose of 3 MU three times per week). The planned maintenance duration was three years or until disease progression or toxicity. From February 1, 2007 to January 27, 2011 266 patients were randomized to maintenance therapy (TV: 89; T: 87, alfa2-IFN: 90). Response and survival were evaluated on an intention-to-treat basis. Responses, relapses and progressions (EBMT criteria) were monitored by an external contract research organization and centrally reassessed. Results: Patient's characteristics at diagnosis such as age, M-protein type, ISS stage, cytogenetics and presence of extramedullary plasmacytomas as well as induction regimen (VTD, TD and VBMCP/VBAD/Bortezomib) and diagnosis-randomization interval were similarly distributed among the 3 arms. The response status at the time of randomization for maintenance after ASCT was CR: 51%, nCR: 12%, PR: 34%, MR 2% and SD: 1% and was well balanced in the three groups. The CR rate with maintenance was improved by 19% with TV, 15% with T and 17% with alfa2-IFN (p=NS). After a median follow-up of 34.9 months, the PFS was significantly longer with TV compared with T and alfa2-IFN (figure 1, p=0.0009). However, OS was not significantly different among the 3 arms. Grade 3 and 4 hematological toxicity was similar (22.2% vs. 16% vs. 21.8%). No peripheral neuropathy (PN) was observed with alfa2-IFN being its frequency similar with TV (12.2%) and T (10.1%). No grade IV PN was observed. Dose reductions for TV, T and alfa2-IFN were required in 33.3%, 33.7% and 19.5% of the patients, respectively. The discontinuation rate due to progressions was not significantly diferent among the three arms (35% vs 24% vs 20%, p=NS). The discontinuation rate due to toxicity was higher with thalidomide compared with TV (30.3% vs. 15.6%, p= 0.08) and with alfa2-IFN (30.3% vs. 18.3%, p=0.17). Patients with high-risk cytogenetics [t(4;14), t(14;16) and/or del 17p] had a trend towards a shorter PFS (p=0.1) and a significantly shorter OS (p=0.03). The incorporation of bortezomib was not able to overcome the poor impact of high-risk cytogenetics. Conclusion: The addition of bortezomib to thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide alone or with single agent alfa2-IFN with no increased toxicity. However, the addition of bortezomib did not overcome the poor impact of high-risk cytogenetics. Disclosures: Rosiñol: Janssen, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:Janssen: Honoraria; Celgene: Honoraria. De La Rubia:Celgene, Janssen: Consultancy, Speakers Bureau. Granell:Janssen: Honoraria; Celgene: Honoraria. de Arriba:Jansen: Honoraria; Celgene: Honoraria. Alegre:Janssen: Honoraria; Celgene: Honoraria. Cibeira:Janssen: Honoraria; Celgene: Honoraria. Mateos:Janssen: Honoraria; Celgene: Honoraria. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. San Miguel:Janssen: Honoraria; Celgene: Honoraria; Onix: Honoraria; Novartis: Honoraria. Bladé:Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria.

Thalidomide As Maintenance Therapy in Multiple Myeloma (MM) Improves Progression Free Survival (PFS) and Overall Survival (OS): A Meta-Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1855-1855 ◽  
Author(s):  
Ajay K. Nooka ◽  
Madhusmita Behera ◽  
Lawrence H. Boise ◽  
Melanie Watson ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Phase Iii ◽  
Cochrane Library ◽  
Free Survival ◽  
Manual Search

Abstract Abstract 1855 Background: Conflicting data regarding the survival benefit of thalidomide maintenance exist in the literature. Recent phase 3 study MMRC.M10 has demonstrated significant toxicity with thalidomide maintenance in combination with steroids. The role of thalidomide maintenance in prolonging PFS and OS is less clear. We conducted a meta-analysis of phase III randomized control trials (RCT) that evaluated thalidomide as maintenance therapy in transplant-eligible patients. Methods: We conducted an electronic literature search of public databases (MEDLINE, EMBASE, Cochrane library) and manual search of conference proceedings of ASH and ASCO. There were seven phase III RCTs that reported the maintenance therapy of thalidomide and survival in MM (Total Therapy 2, IFM 99-02, ALLG trial, HOVON 50, MRC IX trial, NCIC CTG MY.10). One study (Abdelkefi et al., 2008) was retracted and hence not included in the analysis. A formal meta-analysis was conducted using Comprehensive Meta Analysis software (Version 2.0). The outcome data were pooled and reported as hazard ratio (HR). The primary outcome of interest was progression free survival (PFS) and overall survival (OS). Results: A total of 3194 patients (maintenance arm/control arm- 1479/1715, median age 58 years) were evaluated. The 3 year-OS ( HR 0.80, 95% CI 0.70 to 0.917, P=0.001) and 3 year-PFS (HR 0.62, 95% CI 0.55 to 0.69, P=0.000) were superior with maintenance therapy. ‘Steroid and thalidomide’ maintenance therapy was associated with significant OS and PFS improvement (OS HR 0.65, 95% CI 0.47 to 0.89); PFS (HR 0.54, 95% CI 0.44 to 0.67). Overall toxicities with thalidomide maintenance were peripheral neuropathy (PN) 2.184 (95% CI 1.523–3.133) and thromboembolic events (TEE) 1.632 (95% CI 1.076–2.475). Toxicities were increased with thalidomide and steroid maintenance - PN 28.78 (95% CI 1.676–494.13); TEE 2.896 (95% CI 0.76–11.06). Conclusions: Thalidomide as a single agent or in combination with steroids as maintenance therapy improves progression free survival and overall survival. However, high toxicity with steroid combination was observed. Disclosures: Kaufman: Millenium; Onyx; Novartis; Keryx: Consultancy; Merck, Celgene: Research Funding. Lonial:Millennium: Consultancy; Novartis: Consultancy; Celgene: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy.

Interim safety analysis of the randomized phase III PELICAN trial evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line therapy for metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1118-1118
Author(s):  
S. Al-Batran ◽  
S. Saupe ◽  
M. Schmidt ◽  
R. Kreienberg ◽  
B. Otremba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

1118 Background: Treatment of metastatic breast cancer (MBC) focuses on relieving symptoms and extending life. Single-agent therapy is preferred in the first-line setting to reduce the risk of toxicity and maintain quality of life. The PELICAN trial was designed to evaluate efficacy and safety of first-line PLD vs capecitabine at standard approved dosages. Methods: PELICAN is an open-label, multinational, randomized, multicenter trial. MBC Patients (pts) were randomized to receive PLD (50 mg/m2 every 28 days) or capecitabine (1250 mg/m2 BID x 14 days every 21 days) until disease progression or unacceptable toxicity. The primary endpoint was to compare time to disease progression between treatment arms. Toxicity was evaluated continuously. Results: The study is still ongoing, but no longer recruiting. So far, 210 pts (PLD, 105; capecitabine, 105) were evaluated for safety, of whom 131 pts have already completed their treatment (83 for disease progression, 19 for toxicity, 5 died, 24 for other reasons). 90% of pts had ECOG performance status 1 or 2, and 79% were postmenopausal. Mean age was 61.5 years, and 34% received prior adjuvant anthracycline. Pts received a median of 4 cycles of PLD and a median of 5 cycles of capecitabine. Over 90% of pts in both groups experienced at least one adverse event (AE). Grade 3/4 AEs were reported in 99 patients (PLD, 44; capecitabine, 55). Hand foot syndrome (HFS) was the most common AE (grade 3: PLD 35%; capecitabine 19%), followed by diarrhea (grade 3/4: PLD, 0; capecitabine, 13%) and thromboembolic events (PLD, 0%; capecitabine, 9%). Other grade 3/4 AEs affected 1 week in 16%. Conclusions: Overall, first-line monotherapy with PLD or capecitabine at approved doses was maintainable for a median of about 4 months with manageable AEs. Interim safety results of the PELICAN trial show no unanticipated toxicity. Efficacy results will be available once all patients have completed their therapy. [Table: see text]

PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA7507-LBA7507 ◽  
Author(s):  
Luis Paz-Ares ◽  
Filippo De Marinis ◽  
Mircea Dediu ◽  
Michael Thomas ◽  
Jean-Louis Pujol ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Progression ◽  
Performance Status ◽  
Phase Iii ◽  
Controlled Study ◽  
Rank Test ◽  
Induction Treatment ◽  
Double Blind ◽  
Risk Of Death ◽  
Continuation Maintenance

LBA7507 Background: The PARAMOUNT trial showed that pem continuation maintenance therapy significantly reduced the risk of disease progression over plb (HR=0.62; 95% CI: 0.49-0.79; p <0.0001) in patients (pts) with advanced NS NSCLC who had not progressed during pem-cis induction. Here we present the final OS data. Methods: In a double-blind, plb-controlled study, alpha-controlled for OS, 939 pts received induction (4 cycles of pem 500 mg/m2 and cis 75 mg/m2 on d1 of 21d cycles), and 539 pts who had not progressed and had an ECOG performance status (PS) of 0/1 were randomized (2:1) to maintenance pem (500 mg/m2, on day 1 of 21-day cycles) plus BSC or plb plus BSC until disease progression. All received B12, folic acid, and dexamethasone. After 397 deaths, a log-rank test compared OS between arms using anominal α level of 0.0498. Results: Pt characteristics were balanced between arms: median age 61 years; 58% men; 32% PS 0; 95% Caucasian; 86% adenocarcinoma; 45% complete/partial response (CR/PR) to induction. Pem resulted in a statistically significant 22% reduction in risk of death (HR=0.78). The HR was the same when measured from the beginning of induction. Survival improvement was similar for pts with an induction outcome of CR/PR versus stable disease. Conclusions: Pem continuation maintenance therapy offers superior OS compared with plb. These final results confirm that pem-cis induction followed by continuation pem further benefits pts compared with induction therapy alone, offering a change in the treatment paradigm for advanced NS NSCLC. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document