Docetaxel In Metastatic Breast Cancer Research Articles

North East Experience on Pertuzumab, Trastuzumab and Docetaxel in Metastatic Breast Cancer

Purpose: Phase III randomised data from the Cleopatra trial showed significant improvement in median progression free [1] and overall survival [2] with the addition of pertuzumab to docetaxel and traztuzumab. The aims of this audit were:

Is HER2-positive metastatic breast cancer still an incurable disease?

The discovery of the HER2 oncogene was one of the most important advances in breast cancer research. 20 years ago, the advent of trastuzumab 1 Slamon DJ Leyland-Jones B Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344: 783-792 Crossref PubMed Scopus (9343) Google Scholar started a revolution that has continued with the introduction of additional effective targeted agents. Dual anti-HER2 targeting with trastuzumab plus pertuzumab in addition to docetaxel is an unquestionable step forward in the field. Since the publication of the first results of the CLEOPATRA trial in 2012, 2 Baselga J Cortés J Kim S-B et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012; 366: 109-119 Crossref PubMed Scopus (1901) Google Scholar the pertuzumab-based regimen has become the new standard first-line treatment for patients with HER2-positive metastatic breast cancer. 3 Cardoso F Senkus E Costa A et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018; 29: 1634-1657 Summary Full Text Full Text PDF PubMed Scopus (730) Google Scholar , 4 Giordano SH Temin S Chandarlapaty S et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO Clinical Practice Guideline update. J Clin Oncol. 2018; 36: 2736-2740 Crossref PubMed Scopus (124) Google Scholar Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 studyOur analysis shows that the previously observed improvements in overall survival with pertuzumab, trastuzumab, and docetaxel versus placebo, trastuzumab, and docetaxel were maintained after a median of more than 8 years of follow-up. The long-term safety and cardiac safety profiles of pertuzumab, trastuzumab, and docetaxel were maintained in the overall safety population and within crossover patients. HER2-targeted therapy has changed the natural history of HER2-positive metastatic breast cancer, with the dual blockade of pertuzumab and trastuzumab, with docetaxel, demonstrating an 8-year landmark overall survival rate of 37%. Full-Text PDF

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2− Early-stage Breast Cancer

BackgroundWeekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) demonstrated greater efficacy with less toxicity than docetaxel in metastatic breast cancer. We conducted a randomized phase II to compare these regimens as neoadjuvant chemotherapy for HER2− early-stage breast cancer. Patients and MethodsStage I-III human epidermal growth factor receptor-negative (HER2−) breast cancer patients were included in the present trial and received either docetaxel every 3 weeks or nab-paclitaxel on days 1, 8, and 15 every 28 days for 4 cycles, followed by FEC (5-fluorouracil, epirubicin, cyclophosphamide) every 3 weeks for 4 cycles. The primary endpoint was the pathologic complete response (pCR) rate, defined as ypT0 and ypN0. The secondary endpoints were pCR (ypT0/ypTis and ypN0), the clinical response rate (using the Response Evaluation Criteria In Solid Tumors criteria), histologic effect of treatment (using the Japanese Breast Cancer Society classification), breast conservation rate, and adverse events. ResultsA total of 152 eligible patients were enrolled at 6 centers. The baseline characteristics were well balanced. In comparing the 2 regimens (docetaxel/nab-paclitaxel), the pCR rate was 12% and 17% (P = .323). In the Ki67 > 20% group, the pCR rate was greater (24%) for the nab-paclitaxel arm than for the docetaxel arm (16%; P = .432). The most common grade 3/4 adverse event was neutropenia, observed in 40% and 36% of cases in the nab-paclitaxel and docetaxel arms, respectively. The nonhematologic adverse events of any grade were myalgia (34% and 32%), arthralgia (42% and 35%), and peripheral sensory neuropathy (55% and 65%) for the 2 treatment arms. No grade 3/4 peripheral sensory neuropathy was observed in the nab-paclitaxel arm. ConclusionWeekly nab-paclitaxel administered at a dose of 100 mg/m2 showed equivalent efficacy and was well tolerated compared with docetaxel as neoadjuvant therapy. Nab-paclitaxel might be more effective in patients with highly proliferative cancer.

Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer

BackgroundThe phase III CLEOPATRA study demonstrated that combining pertuzumab with trastuzumab plus docetaxel significantly improves progression-free and overall survival in previously untreated HER2-positive metastatic breast cancer. Here, we report health-related quality-of-life (HRQoL) results from CLEOPATRA. Patients and methodsParticipants were randomly assigned to pertuzumab or placebo, each given with trastuzumab plus docetaxel every 3 weeks. Pertuzumab and trastuzumab were administered until progression and six or more docetaxel cycles were recommended. Time from randomization to a ≥5-point decrease in Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was analyzed as a prespecified secondary end point. A post hoc exploratory analysis investigated time to ≥2-point deterioration in Breast Cancer Subscale (BCS) score. ResultsTime to ≥5-point decline in TOI-PFB did not differ significantly between the pertuzumab and placebo arms [hazard ratio (HR), 0.97; P = 0.7161]. The median times to TOI-PFB deterioration were 18.4 and 18.3 weeks, respectively (approximately six cycles). The mean TOI-PFB declined slightly until week 18 and recovered thereafter. Pertuzumab increased time until BCS deterioration versus placebo (median 26.7 versus 18.3 weeks; HR, 0.77; P = 0.0061). ConclusionsCombining pertuzumab with trastuzumab and docetaxel had no adverse impact on HRQoL and may prolong time to worsening of breast cancer-specific symptoms.

Capecitabine maintenance therapy after docetaxel/capecitabine combination chemotherapy in patients with metastatic breast cancer.

e12018 Background: Addition of capecitabine to docetaxel improves survival outcomes compared with single agent docetaxel in metastatic breast cancer (MBC). In this study we analyzed efficacy of maintenance therapy with single agent capecitabine after six cycles of docetaxel/capecitabine chemotherapy in MBC patients. Methods: Patients with metastatic HER2 negative breast cancer were included. Six cycles of docetaxel (75mg/m2 q3wk) / capecitabine (1650mg/m2/day on days 1 to 14) followed by capecitabine (2000 mg/m2/day on days 1 to 14) were administered. Demographic features, progression free (PFS) and overall survival (OS) and response to treatment were recorded. Results: Fifty-four patients were included. Thirty-five patients (65%) were postmenopausal, and 40 (74%) were ER/PR positive. Median age was 53 (range 28 – 70). Number of metastatic sites was one in 23 patients, two in 21, three or more in 10 patients. Most common metastatic sites were bone (67%), lymph nodes (33%), lungs (30%), liver (13%); 13 patients (24%) had bone only disease. Forty-four (81.5%) patients received treatment in first-line, 10 (18.5%) received in second line setting. Median number of cycles applied (including docetaxel/capecitabine combination) was 9 (range 2 – 31, total 576). Median PFS was 9 months (10.4 for hormone receptor positive, 7.3 for negative patients) and median OS was 28 months. Objective response was assessable in 38 patients. Overall response rate (partial + complete response) was 42.6% (95% CI 29.6 – 55.6) with 1 complete response. Toxicities were evaluated in 41 patients; grade 3/4 neutropenia was observed in 10% and grade 3/4 hand-foot syndrome was observed in 24% of patients. Dose reduction was performed in capecitabine in 37%, and in docetaxel in 20% of patients. Conclusions: Maintenance with single agent capecitabine therapy after six cycles of docetaxel/capecitabine chemotherapy is an effective and tolerable treatment option for HER2 negative MBC patients.

Simulations to Assess Phase II Noninferiority Trials of Different Doses of Capecitabine in Combination With Docetaxel for Metastatic Breast Cancer

A phase II trial in metastatic breast cancer (MBC) (NO16853) failed to show noninferiority (progression-free survival, PFS) of capecitabine 825 mg/m2 plus docetaxel 75 mg/m2 to the registered capecitabine dose of 1,250 mg/m2 plus docetaxel 75 mg/m2. We developed a modeling framework based on NO16853 and the pivotal phase III MBC study, SO14999, to characterize the link between capecitabine dose, tumor growth, PFS, and survival to simulate response to a range of capecitabine doses and determine a minimum capecitabine dose noninferior to 1,250 mg/m2. Simulation showed NO16853 had little power to demonstrate noninferiority (69%). The power reached 80% with a 1,000 mg/m2 starting dose and an increased number of PFS events. A starting dose of 1,000 mg/m2 could be established as noninferior in terms of efficacy to the registered dose in the second-line MBC setting, with a potentially improved safety, in line with medical practice.

Weekly docetaxel in patients with metastatic breast cancer: A Bangladeshi perspective.

e11533 Background: Docetaxel has demonstrated high antitumor activity in first and second line treatment of metastatic breast cancer. Usually it is administrated three weekly at a dose of 75mg/ m2. We evaluated the efficacy and toxicity of Docetaxel in metastatic breast cancer in weekly bases. This study analyzed the efficacy and toxicity of docetaxel given weekly. Methods: Thirty eight patients with metastatic breast cancer received docetaxel, 35 mg/m2 weekly for six weeks, followed by two weeks interval. Additional cycles (three weeks' treatment, two weeks' rest) were given until disease progression or death. All patients had received prior chemotherapy. Of them 32 patients previously received anthracycline-containing regimens and 5 patients had received taxane based regimens. Results: Out of thirty eight patients thirty seven were evaluable. There was one complete response (3%), 11 patient has partial responses (30%), 17 patients with stable disease (46%) and six with disease progression (16%). Overall response rate was 78%. Median progression-free survival was 9.2 months. Three patients showed grade 3 neutropenia. 14 showed grade 3 alopecia, and various grade 1–2 non-haematological toxicities were observed. Treatment was delayed in two patients due to haemalotoxicity and stopped in one patient due to painful nail toxicity. Conclusions: Docetaxel is effective in three weekly regimens. In our study we found weekly docetaxel is as effective as the previous regimen. The efficacy of weekly docetaxel (35 mg/m2) can be an effective schedule for metastatic breast cancer who has received chemotherapy previously. The toxicity in this regimen is very low and manageable.

Quality of life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer.

598^ Background: CLEOPATRA compared the efficacy and safety of the HER2 dimerization inhibitor pertuzumab (P) plus trastuzumab (T) and docetaxel (D) with placebo (Pla)+T+D in HER2-positive 1st-line MBC. Pts in both arms received a median of 8 cycles of D; Pla/P+T was continued until progressive disease (PD). The safety profile in both arms was similar with a substantial decrease in adverse events (AEs) once chemotherapy finished. The independently assessed progression-free survival was significantly improved with P+T+D compared with Pla+T+D; objective response and duration of response were also improved with P+T+D (Baselga NEJM 2012). Here we report health-related quality of life (HRQoL) data from CLEOPATRA. Methods: Time to deterioration of HRQoL was evaluated using the FACT-B questionnaire and defined as decrease from baseline (BL) of ≥5 points in the TOI-PFB subscale score. Female pts completed questionnaires every 3rd cycle of therapy within 3 days before each tumor assessment until independently determined PD. An exploratory analysis investigated time to deterioration in breast cancer symptoms and functions. Results: 56.7% (Pla+T+D) and 59.5% (P+T+D) of pts experienced deterioration of HRQoL during the study based on TOI-PFB. The median time to deterioration was 18.3 vs 18.4 wks (~6 cycles) (HR 0.97; P = .7161). At Cycle 6, the mean reduction in TOI-PFB score from BL was –3.5 (Pla+T+D) vs –3.0 (P+T+D). At subsequent cycles, when most pts had discontinued D, mean reductions were smaller, suggesting that after an early decline patients’ scores improved slightly. Overall, mean changes were small in both arms. Compliance with completion of the FACT-B questionnaire was ≥75% beyond the 1st year in both arms. An exploratory analysis suggested that time to deterioration in BCS score, which measures symptoms and issues relevant in breast cancer, was delayed with P+T+D (18.3 vs 26.7 wks; HR 0.77; P = .0061). Conclusions: Combining P with T+D appears to have no detrimental effect on HRQoL. Results suggest that P+T+D is associated with a substantial delay in the time to deterioration in BCS score as would be expected given the improved efficacy and the low incidence of AEs once D is discontinued.

251 Retrospective Analysis of the Relative Efficacy and Toxicity of Nab-paclitaxel and Docetaxel in Metastatic Breast Cancer

251 Retrospective Analysis of the Relative Efficacy and Toxicity of Nab-paclitaxel and Docetaxel in Metastatic Breast Cancer

Expression of β-tubulin III and Survivin in Advance Stage Breast Cancer Correlates with Chemotheraputic Effects of Docetaxel

To investigate the relationship between the expression of β-tubulin III and survivin in advanced breast cancers and chemotherapeutic effects of docetaxel. Clinical pathological data of 74 patients with advanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of β-tubulin III and survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverse effects of docetaxel. The positive expression rate of β-tubulin III was 38.1% (32/84), while that of survivin was 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients with the positive expression of β-tubulin III or/and survivin was significantly lower than for those with negative expression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and 2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effects were myelosuppression, alimentary canal response and alopecia, no differences being observed between groups. The combined detection of β-tubulin III and survivin is a predictive index for chemotherapy effects of docetaxel in metastatic breast cancer.

Efficacy and safety of bevacizumab in combination with docetaxel for the first-line treatment of elderly patients with locally recurrent or metastatic breast cancer: Results from AVADO

BackgroundOncologic treatment in elderly patients is challenging, due to comorbidities, often impaired organ function, limited clinical trial evidence, inadequate guidelines and no consistent ‘elderly’ definition. We report exploratory sub-analyses of safety and efficacy in elderly patients, defined as ⩾65years old, in AVastin And DOcetaxel (AVADO) receiving first-line bevacizumab plus docetaxel for metastatic breast cancer (mBC). Patients and methodsPatients with HER2-negative, locally recurrent or mBC were randomised to 3-weekly docetaxel (100mg/m2) with placebo, bevacizumab 7.5mg/kg or bevacizumab 15mg/kg, for 9 cycles or until disease progression or unacceptable toxicity. Patients had no prior chemotherapy for mBC. ResultsProgression-free survival (PFS) was increased with bevacizumab in the elderly subpopulation (n=127), the effect being greater with higher dose (hazard ratio=0.63 [95% confidence interval (CI) 0.383–1.032] versus 0.76 [95% CI: 0.46–1.262], respectively). PFS was numerically similar in the elderly and overall populations, but the former failed to achieve statistical significance. Overall response rates for docetaxel plus placebo, bevacizumab 7.5mg/kg and 15mg/kg were 44.7%, 36.6% and 50.0%, respectively. Effects on survival were not statistically significant. Bevacizumab was well tolerated in elderly patients, the most common adverse effects were neutropenia and febrile neutropenia; there was no excess of grade⩾3 cardiovascular events. There was no clear correlation between baseline hypertension and its development during study treatment. ConclusionsIn this exploratory sub-analysis in AVADO, bevacizumab plus docetaxel showed efficacy in elderly patients similar to the overall study population. There were no unexpected safety signals in patients aged 65years or older.

Randomized, Placebo-Controlled, Double-Blind, Phase II Study of Axitinib Plus Docetaxel Versus Docetaxel Plus Placebo in Patients With Metastatic Breast Cancer

This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC). Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP). In all, 168 patients were enrolled; 112 were randomly assigned to axitinib and 56 to placebo. Median TTP was numerically longer in the combination arm than in the placebo arm (8.1 v 7.1 months), but this difference was not statistically significant (hazard ratio, 1.24; 95% CI, 0.82 to 1.87; one-sided P = .156). The difference in median TTP was greatest among patients who had received prior adjuvant chemotherapy (9.2 v 7.0 months; P = .043, prespecified subgroup analysis). Objective response rate was higher in the combination arm (41.1% v 23.6%; P = .011). The most common grades 3 to 4 treatment-related adverse events (combination/placebo) included diarrhea (10.8%/0%), fatigue (10.8%/5.4%), stomatitis (12.6%/1.8%), mucositis (9.0%/0%), asthenia (7.2%/0%), and hypertension (4.5%/0%). Three patients in the combination arm experienced serious thromboembolic events (one death). Febrile neutropenia was more frequent in the combination arm (15.3% v 7.1%); rates of other hematologic toxicities were comparable. Increased toxicity with axitinib was generally managed by dose reduction and/or growth factor support. The addition of axitinib to docetaxel did not improve TTP in first-line MBC treatment. Combination therapy may be more effective in patients previously exposed to adjuvant chemotherapy.

Tumor growth modeling from clinical trials reveals synergistic anticancer effect of the capecitabine and docetaxel combination in metastatic breast cancer

Most of the cancer chemotherapy treatments employ drugs in combination. For combination treatments, it is relevant to assess interaction between two or more anticancer agents used in clinics. Based on clinical data and using modeling techniques, the work analyzes the pharmacodynamic interaction between capecitabine and docetaxel used in combination in metastatic breast cancer. We developed mathematical models to describe tumor growth inhibition profile under treatment based on Phase II and Phase III clinical data of capecitabine and docetaxel in metastatic breast cancer. Model parameters were estimated by population approach with NONMEM(®) on single-agent and combination data. Simulations were performed using MATLAB. Capecitabine and docetaxel combination in metastatic breast cancer results in a synergistic effect as compared with the simple additive effects of single-agent treatments. Docetaxel is more efficient than capecitabine at the start of treatment but develops resistance faster. Modeling revealed no resistance of capecitabine for the combination data. Modeling could be a powerful tool to design the most advantageous combination regimen for capecitabine and docetaxel in metastatic breast cancer in order to increase the time before regrowth and decrease the tumor size at regrowth.

A Modeling and Simulation Framework to Support Early Clinical Drug Development Decisions in Oncology

A Modeling and Simulation Framework to Support Early Clinical Drug Development Decisions in Oncology

Phase II Trial of OGX-011 in Combination with Docetaxel in Metastatic Breast Cancer

Clusterin is an antiapoptotic protein activated in response to cellular stress. OGX-011 is a second-generation antisense oligonucleotide that inhibits clusterin expression. The primary objective of this phase II trial was to assess the safety and efficacy of the combination of OGX-011 and docetaxel for metastatic breast cancer. Women with measurable metastatic breast cancer and <or=1 chemotherapy regimen were eligible. Three loading doses of OGX-011 640 mg i.v. followed by weekly OGX-011 and docetaxel 75 mg/m(2) (every 3 weeks) were given. A two-stage design was used with a hypothesis of H(0) <or=35% and H(a) >or=55%. Objective response in >or=6 of the first 14 patients was required for the trial to continue to the second stage. Fifteen patients were enrolled. A median of six cycles were delivered (range, 2-10). Five partial responses were confirmed for a 33% response rate (95% confidence interval, 11.8-61.6%) with a further 9 (60%) patients showing stable disease. The median duration of stable disease was 9.3 months. The median time to progression was 8 months (95% confidence interval, 5.62-9.43 months). Toxic effects were similar to those with single agent docetaxel. Although serum clusterin decreased on treatment, there was no relationship observed between the magnitude of decrease and response. The combination of OGX-011 and docetaxel at 75 mg/m(2) is well tolerated and clinical activity was seen in these patients with metastatic breast cancer, but there was an insufficient number of responses to meet the criteria for proceeding to the second stage of accrual.

Randomized multicenter phase II trial of navcap (vinorelbine and capecitabine) versus navcap followed by weekly docetaxel as first line treatment in HER-2/neu negative metastatic breast cancer patients: updated results.

Abstract Abstract #6116 Background: Capecitabine (C), vinorelbine (V) and docetaxel (D) are effective in the 1st line treatment of metastatic breast cancer (MBC). Based on the efficacy and the tolerability of Navcap (M. Ghosn et al. Antican Res 2006) and Navcap followed by docetaxel in MBC (M. Ghosn et al. Can Chemother Pharmacol 2008), we initiated a randomized phase II study. Primary Objective: To compare the objective response rate (ORR) of 8 cycles of Navcap vs. 4 cycles of Navcap followed by 12 weekly Docetaxel in the 1st line setting of MBC. Methods: Patients (pts) with measurable disease, no prior chemotherapy in MBC and Her-2/neu negative are eligible. All pts will receive Navcap (V 25 mg/m2 on d1 &amp; d8 as IV push and C 825 mg/m2 bid D1-14 q3w) for 4 cycles. Pts progressing under treatment with Navcap are withdrawn and receive Docetaxel as 2nd line treatment. Pts responding or stable after completing 4 cycles of Navcap are randomized to: Arm A (4 Navcap) or Arm B (12 weekly Docetaxel 25 mg/m²/week). Results: From July 2004 to June 2008, a total of 110 pts were enrolled. At the time of this analysis 78 pts had completed the first 4 cycles of Navcap with an ORR of 55% (CR 13%) and a stable disease of 19%. 20 pts (26%) were excluded from randomization due to PD. 58 pts were randomized: Arm A: 30 pts and Arm B: 28 pts. Patient characteristics are summarized in table 1. All pts were evaluable for response with objective response rates of 70% &amp; 78% in Arms A and B respectively. The median TTP &amp; overall survival are 10 &amp; 34 months in Arm A; 11 &amp; 34 months in Arm B. Statistical comparison for efficacy &amp; survival outcomes will be done once all pts are randomized &amp; long term follow-up is available. All pts were evaluable for toxicity. The majority of adverse events were mild. Arm A: Gr 4 neutropenia (3%), Gr 3 anemia (6%). Arm B: Gr 3-4 anemia (9.6%), Gr 3 leukopenia (4.8%) &amp; Gr 2 alopecia (14.3%). Conclusions: These preliminary results show that Navcap confirms its high response rate in 1st line treatment for HER-2/neu negative MBC. By the date of the meeting all pts will be randomized and will have completed their treatment. Mature data will be presented accordingly. (Protocol initiated &amp; coordinated by the Cancer Research Group/Collaborative Group, Beirut–Lebanon).&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6116.

Non-pegylated liposomal doxorubicin and docetaxel in metastatic breast cancer: final results of a phase II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumor activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as single agent or in combination with cyclophosphamide, but there is limited experience with the combination of NPLD and taxanes. This phase II study was performed to evaluate the efficacy and safety of the NPLD and docetaxel in patients with metastatic breast cancer. A total of 51 patients were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) in 3-weeks intervals for up to eight cycles. The overall response rate was 50% and 78% of patients derived a clinical benefit. Median time to progression and overall survival were 10.0 months (95% CI, 6.9-13.1 months) and 25 months (95% CI, 22.1-29.8 months), respectively. Median duration of response was 12.0 months (95% CI 7.1-16.9). The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents and of anthracycline/taxane combinations. There were no symptomatic cardiac averse events and mild asymptomatic LVEF changes were reported in five patients. The combination of NPLD and docetaxel is well tolerated and has high antitumour activity in MBC patients.

Weekly Vinorelbine versus Docetaxel for Metastatic Breast Cancer after Failing Anthracycline Treatment

Background: Vinorelbine and docetaxel are active in anthracycline-pretreated, metastatic breast cancer. We compared their efficacy. Patients and Methods: Patients were randomized to receive weekly vinorelbine (VIN) or weekly docetaxel (DOC), 6 weekly doses per 8-week cycle, with optional crossover (X-DOC vs. X-VIN. The primary end point was time to progression (TTP) on initial treatment. Remission induction, survival, and quality of life were secondary end points. Results: Among 122 poor risk patients, a non-significant trend for better TTP was seen for DOC, both on initial and on crossover treatment. Responses were seen on either treatment, but progression was more common with VIN than with DOC, while more patients had a response with X-DOC than with X-VIN. Survival was identical in those receiving only the initial VIN vs. DOC and in the subgroups receiving crossover treatments. Grade 3–4 toxicity, especially hematological toxicity resulting in treatment delay, was more common with VIN. Non-graded toxicity contributed to abandoning DOC. Quality of life scores reflected worse results in patients crossing treatment arms, in either direction. Conclusions: DOC showed marginally better activity but did not improve TTP or other endpoints over VIN in this poor risk population.

Phase II pilot results of imatinib mesylate with weekly docetaxel in metastatic breast cancer

1090 Background: Imatinib mesylate (G) is a potent tyrosine kinase inhibitor of platelet derived growth factor receptor (PDGFR), c-KIT, and bcr/abl. PDGFR signaling regulates interstitial tumor pressure enhancing tumor drug delivery and effects. This phase II pilot evaluates the feasibility, toxicity, and efficacy of imatinib with weekly docetaxel as a strategy to potentiate docetaxel in metastatic breast cancer (MBC). Methods: Eligibility: 0–1 regimens for MBC, > 6 months from prior adjuvant taxanes, measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: Docetaxel 30 mg/m2 IV days 1, 8 and 15 q28 with G 600 mg QD. After the first 14 pts, G was decreased to 400 mg in the remaining 19 pts. Response evaluations were every q 8 wks. Following 6 cycles of therapy, pts with SD or better continued maintenance G until PD. Results: 33 pts are evaluable for toxicity. Median age 58 (38–82), ECOG PS 0–18, PS 1–14 pts. 49% ER-/PR- and 79% HER2 neg. 61% had metastases in > 2 visceral sites with lung predominating 42%. 55% received therapy 1st line and 42% as 2nd-line. 13 pts had prior taxanes of which 70% were treated 2nd-line. Hematologic toxicity was mild with G3/4 neutropenia 12%, anemia 9%; 1 pt with febrile neutropenia. G3/4 nonhematologic toxicity consisted of fatigue 27% and GI toxicity prompting G dose modification to 400 mg after the first 14 pts. Despite the lower G dose, the GI events remained distributed equally between the 600/400 mg G doses: G3/4 diarrhea 21% (4/3), nausea 18% (4/2), vomiting 12% (2/3), anorexia 6% (1/1) 22 pts required hospitalizations, 9 treatment related (GI toxicity 4, febrile neutropenia 1, pleural effusion 2, pneumonia 2), 2 other, and 11 due to progression. Median # of cycles was 3 (1.5 - 12.5). 5 pts went on to maintenance G with a median of 6 cycles and 2 remain on maintenance G. 4 of 18 evaluable pts (12%) had PRs, 8 pts had SD, and 6 pts progressed. 11 pts were not evaluable and responses unknown in 4 pts. Median time to progression and overall survival were 3 and 10 months respectively. Conclusions: Imatinib with docetaxel is associated with significant GI toxicity, despite G dose modification to 400 mg daily. No therapeutic advantage for the addition of imatinib to weekly docetaxel in MBC was evident. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, Novartis, sanofi-aventis

Randomized comparison of weekly or every-3-week (q3w) nab-paclitaxel compared to q3w docetaxel as first-line therapy in patients (pts) with metastatic breast cancer (MBC)

1032 Background: 130-nM albumin-bound (nab™) paclitaxel combines paclitaxel with albumin without solvents or altering either component. A cross analysis of 2 clinical trials comparing solvent-based (SB) paclitaxel 175 mg/m2 q3w to nab- paclitaxel (Gradishar et al, JCO, 2005) and SB docetaxel (Jones et al, JCO, 2005) suggested comparable antitumor activity between nab-paclitaxel and SB docetaxel and better tolerability with nab-paclitaxel in pts with MBC. The aim of this study was to compare the toxicity and antitumor activity of 3 regimens of nab-paclitaxel (q3w and 2 weekly) with each other and that of SB docetaxel in MBC. Methods: In this open-label study, first-line pts with MBC were randomly assigned to nab-paclitaxel 300 mg/m2 q3w (A); nab-paclitaxel 100 mg/m2 (B) or 150 mg/m2 (C) days 1, 8, and 15, q28 days (q 3/4 w); or SB docetaxel 100 mg/m2 q3w (D). The primary endpoints were overall response rate (complete response + partial response, evaluated q8w) and toxicity. Progression-free survival (PFS) was also determined. Results: 302 pts (median age, 54 years; 99% Caucasian; 75% postmenopausal; ECOG PS =2 [94% =1]) either had at least 2 response assessments (94%) or had discontinued due to PD (6%). The efficacy results are shown in the Table . Neutropenia (N) was greater with D than with A, B, or C (p &lt; 0.001). Grade 4 N was: A) 4%, B) 3%, C) 7%, and D) 74%. Febrile neutropenia (FN) was: A) 1%, B) 1%, C) 1%, and D) 7%. Gr 3 peripheral neuropathy was: A) 14%, B) 7%, C) 12%, and D) 5%. Conclusions: The response rates of q3w nab-paclitaxel and solvent-based docetaxel were comparable. Q 3/4 W nab-paclitaxel resulted in higher response rates than solvent-based docetaxel. Grade 4 N and FN were less frequent with nab-paclitaxel as compared with solvent-based docetaxel. To date, all 3 nab-paclitaxel regimens have a longer PFS than SB docetaxel although the data are not yet mature (33% of events). Final data for a radiological review of response data, PFS, and toxicity will be presented. [Table: see text] No significant financial relationships to disclose.