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]

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial

2001 ◽  
Vol 19 (6) ◽  
pp. 1707-1715 ◽  
Author(s):  
Jacek Jassem ◽  
Tadeusz Pieńkowski ◽  
Anna Płuzańska ◽  
Svetislav Jelic ◽  
Vera Gorbunova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Time To Progression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m2 followed 24 hours later by paclitaxel 220 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P < .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in elderly metastatic breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19565-19565 ◽  
Author(s):  
P. R. Dufour ◽  
F. Rousseau ◽  
N. Meyer ◽  
T. Delozier ◽  
D. Serin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
First Line ◽  
Grade 3 ◽  
Line Chemotherapy

19565 Background: Although the majority of metastatic breast cancer (MBC) patients (pts) responds to endocrine therapy, treatment failure is a concern, as well as front-line therapy for pts with ER/PR negative disease.The combination of anthracyclines (A) and cyclophosphamide (C) is active in younger pts, but cardiac toxicity of A in elderly MBC pts has to be considered. Pegylated liposomal doxorubicin (PLD) (Caelyx®) is active in MBC and has much less cardiotoxicity than A, and we present the preliminary data of the PLD/C in elderly MBC pts. Methods: This was a multicentric phase II trial. Inclusion criteria included: pts aged between 65 and 75, histologically proven measurable MBC, ECOG PS 0–1, LVEF = 50%, first-line chemotherapy for MBC. Prior adjuvant chemotherapy was allowed if stopped for = 6 or 12 months without and with anthracyclines, respectively. Endocrine therapy either in the adjuvant or metastatic setting had to be stopped for = 1 month. All pts gave a written informed consent. The treatment schedule was : PLD 40mg/m2 and C 500mg/m2 d1 every 4 weeks. Efficacy as well as response duration and tolerance were the primary and secondary end-points, respectively. Results: 35 patients were enrolled (Median age 71.3, range 65.6–75.9). A total of 166 cycles have been administered. The median number of cycles was 6 (range 1–9). No toxic death was reported, one patient died of diabetes mellitus decompensation. No congestive heart failure or decrease in LVEF was reported, although 1 pt experience grade 3 dyspnea and stopped treatment. Other (gr3–4) NCI-CTC toxicity included: neutropenia in 7 (gr3) and 3 (gr4) pts; gr3 mucositis (4). No febrile neutropenia was reported. Grade 3 hand-foot syndrome occurred in 1 pt, whereas treatment was stopped due to a generalized rash in 1 pt. An objective response (CR + PR) was achieved in 10 (28,6%) pts (1 CR and 8 PR), and a disease control in 24 (68.6%) with a progression free survival of 8.8 months and a median survival of 20.4 months Conclusions: The LPD-C combination is active in elderly MBC pts, with an acceptable toxicity profile. No significant financial relationships to disclose.

Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
G. Sledge ◽  
K. Miller ◽  
C. Moisa ◽  
W. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

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.

Docetaxel and Doxorubicin Compared With Doxorubicin and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer: Results of a Randomized, Multicenter, Phase III Trial

2003 ◽  
Vol 21 (6) ◽  
pp. 968-975 ◽  
Author(s):  
Jean-Marc Nabholtz ◽  
Carla Falkson ◽  
Daniel Campos ◽  
Janos Szanto ◽  
Miguel Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Complete Response ◽  
Phase Iii ◽  
Cardiac Events ◽  
First Line ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose: This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC). Patients and Methods: Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 (n = 214) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (n = 215) on day 1, every 3 weeks for up to eight cycles. Results: Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P = .014; median TTF, 25.6 v 23.7 weeks; log-rank P = .048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P = .009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v 41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P < .001; 8% v 2%, P = .01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%). Conclusion: AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.

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