Locally Recurrent Or Metastatic Breast Cancer Research Articles

196P Final analysis of PUFFIN: A phase III, randomised double-blind, placebo (Pla)-controlled study of pertuzumab, trastuzumab and docetaxel (PHD) for Chinese patients (pts) with previously untreated HER2-positive locally recurrent or metastatic breast cancer (LR/MBC)

CLEOPATRA (NCT00567190) showed PHD significantly improved progression-free and overall survival (PFS/OS) in pts with previously untreated HER2-positive LR/MBC. PUFFIN (NCT02896855) was a Chinese bridging study to assess consistency of efficacy of PHD with CLEOPATRA. The primary analysis showed efficacy was consistent with CLEOPATRA and safety, with the known P profile. This final analysis presents a further 20+ months of follow-up of efficacy and adverse event (AE) reporting.

Efficacy and safety of adding an agent to bevacizumab/taxane regimens for the first-line treatment of Her2-negative patients with locally recurrent or metastatic breast cancer: results from seven randomized controlled trials.

BackgroundThe combined therapy of bevacizumab (BEV) with taxane (paclitaxel or docetaxel) has shown an improvement on progression-free survival (PFS) and objective remission in Her2-negative patients with locally recurrent or metastatic breast cancer (LR/MBC). However, there was no benefit in overall survival (OS). The aim of this study was to evaluate the efficacy and safety of adding an agent to the BEV/taxane regimens for the treatment of Her2-negative patients with LR/MBC in a first-line setting.Materials and methodsWe searched PubMed, Web of Science, EMBASE, EBSCO, and the Cochrane Library databases for eligible trials. A meta-analysis was performed using Review Manager 5.0 freeware package. We calculated the hazard ratio (HR) for PFS and OS. The odds ratio (OR) was used to calculate objective response rate (ORR) and grade 3/4 drug-related adverse events. The heterogeneity of study outcomes was calculated by the χ2 test or I2 statistics.ResultsA total of 1,124 patients from seven randomized controlled trials were analyzed. Our meta-analysis showed that the ORR was significantly improved in the BEV/taxane-based triplet group when compared with the BEV/taxane-based doublet group (OR =1.31, 95% confidence interval [CI]: 1.03–1.67, P=0.03). A subset analysis showed that a similar result was achieved in the triplet group in which a cytotoxic agent was added (OR =1.46, 95% CI: 1.09–1.95, P=0.01). However, the PFS and OS had no statistically significant differences between the two groups (HR =0.87, 95% CI: 0.68–1.13, P=0.31; HR =0.98, 95% CI: 0.82–1.16, P=0.78, respectively). Regarding safety, thromboembolic events, fatigue, and diarrhea (all $grade 3) were more frequently observed in the BEV/taxane-based triplet group (OR =3.8, 95% CI: 1.86–7.79, P=0.0003; OR =1.55, 95% CI: 1.05–2.27, P=0.03; OR =2.1, 95% CI: 1.29–3.41, P=0.003, respectively). Other toxic effects had no statistically significant differences between the two groups.ConclusionOur results showed that adding an agent to BEV/taxane treatment regimens did not significantly improve PFS and prolong OS, except for conferring a significant advantage toward improved ORR in the first-line therapy for Her2-negative patients with LR/MBC. However, its side effects are predictable and manageable.

Abstract P3-06-09: Plasma biomarker analysis in patients with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X)

Abstract Background The phase II ATX trial aimed at evaluating safety and efficacy of first-line AT or ATX for HER2-negative LR/MBC (NTR1348; BOOG 2006-06). Plasma samples were collected for investigation of circulating proteins involved in angiogenesis and their possible association with therapy outcome. We here report the prognostic value of plasma VEGF-A, soluble (s)VEGFR-2, ANG2, sTIE2, IL6, IL8 and CA9 at baseline (C1D1) and their changes after cycle 1 (C2D1). Methods 312 patients were randomized 1:1 to AT (T 90 mg/m2 d1, 8, 15 & A 10 mg/kg d1, 15 q4w x 6 cycles → A 15 mg/kg d1 q3w for next cycles) or ATX (T 90 mg/m2 d1, 8, A 15 mg/kg d1 & X 825 mg/m2 bid d1–14 q3w x 8 cycles → A & X at same dose q3w for next cycles). Plasma proteins were measured by immunoassays (R&D Systems and MSD). The association of (continuous) protein levels on C1D1 and their changes on C2D1 with response, PFS and OS were evaluated by Mann-Whitney U test and univariate Cox regression analysis. Results The biomarker cohort (n=181) and trial cohort had similar baseline characteristics and clinical outcome. After a median follow-up of 46 months, there were 178 (98%) PFS events and 152 (84%) deaths. On C1D1, levels of ANG2 and sTIE2 were significantly higher in patients with hormone-receptor positive disease compared to those with triple-negative disease (p=.025 and p=.001, respectively). A high level of VEGF-A was noted in patients with visceral metastases (p=.028) and those with an increasing number of metastatic sites (p=.017). High levels of ANG2, IL6, IL8 and CA9 were significantly associated with poor PFS and OS (Table 1). Protein levels were not associated with response. Table 1. Association of circulating proteins at baseline with PFS and OSPFS HR (95%CI)PFS p-valueOS HR (95%CI)OS p-valueANG22.3 (1.0-4.9).043.1 (1.4-7.0).007IL61.6 (1.1-2.3).021.9 (1.3-2.8).001IL81.9 (1.3-2.8).0012.8 (1.8-4.3)<.001CA91.8 (1.2-2.7).0061.9 (1.3-2.9).002 On C2D1, levels of all proteins, except for IL6, had significantly changed. Whereas VEGF-A, ANG2, sTIE2 and IL8 decreased significantly, sVEGFR2 and CA9 showed a significant increase. The median relative change of both IL8 and sVEGFR2 was significantly different between patients having CR/PR vs. SD/PD (for IL8: -19.4% vs. 22.3%, p=.001 and for sVEGFR2: 6.5 vs. 2.1%, p=.01). A large relative increase in CA9 level was associated with better PFS (HR = 0.36, 95% CI, 0.19 – 0.68, p=.002) and OS (HR = 0.50, 95% CI, 0.27 – 0.94, p=.03). All patients had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions In patients with HER2-negative LR/MBC receiving first-line bevacizumab-containing chemotherapy, high baseline plasma levels of ANG2, IL6, IL8 and CA9 indicate a high risk for poor PFS and OS. These proteins might be useful for stratification according to prognosis. Moreover, relative decrease in IL8 and increase in sVEGFR2 on C2D1 are associated with response, whereas a large relative increase in CA9 is associated with better PFS and OS. Changes in these proteins after one cycle might be early indicators of efficacy of bevacizumab combined with chemotherapy. Financial support from Roche Netherlands. Citation Format: Siu W Lam, Nienke M Nota, Steffen M de Groot, Agnes Jager, Monique MEM Bos, Sabine C Linn, Joan van den Bosch, Hans J Braun, Ankie MT van der Velden, Maartje Los, Johanneke EA Portielje, Judith R Kroep, Aafke H Honkoop, Carolien H Smorenburg, Bea Tanis, Johanna MGH van Riel, Jetske M Meerum Terwogt, Marien O den Boer, Joep Douma, Frank Jeurissen, Johan Berends, Harm van Tinteren, Epie Boven. Plasma biomarker analysis in patients with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-09.

Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: A multicentre, open-label, randomised phase 2 trial

BackgroundThe addition of bevacizumab to paclitaxel or capecitabine has demonstrated improved progression-free survival (PFS) and objective response rate (ORR) as compared with chemotherapy alone in patients with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC). We evaluated the efficacy and safety of first-line therapy of paclitaxel and bevacizumab with or without capecitabine in patients with HER2-negative LR/MBC. MethodsIn this multicentre, open-label, randomised phase II trial, women with HER2-negative LR/MBC were randomly assigned in a 1:1 ratio to paclitaxel (90mg/m2 intravenously [IV] on days 1, 8, and 15) and bevacizumab (10mg/kg IV on days 1 and 15) every 4weeks for six cycles, followed by bevacizumab (15mg/kg IV on day 1) every 3weeks (AT) or to paclitaxel (90mg/m2 IV on days 1 and 8), bevacizumab (15mg/kg IV on day 1) and capecitabine (825mg/m2 orally twice daily on days 1–14) every 3weeks for eight cycles, followed by bevacizumab and capecitabine at the same doses every 3weeks (ATX). The primary end-point was investigator-assessed PFS. Secondary end-points included ORR, duration of response, overall survival (OS) and safety. Exploratory analyses were conducted to evaluate the impact of capecitabine on OS and to validate a novel prognostic model. This trial is registered with EudraCT, number 2006-006058-83. FindingsMedian PFS was significantly longer in ATX as compared with AT (11.2months versus 8.4months; stratified hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.41–0.67; p<0.0001). The ORR in ATX patients with measurable disease (n=268) was higher than that in AT (69% versus 51%; p=0.01). The median duration of response was 6.8 versus 5.4months for, respectively, ATX and AT (p<0.0001). Median OS was 24.2months for ATX and 23.1months for AT (p=0.53). The increased rate of grade 3–4 adverse events related to the addition of capecitabine, being hand-foot syndrome (34% versus 0% for AT) and neutropenia (20% versus 12% for AT), generally did not preclude continuation of treatment. Exploratory analyses indicated that 1) patients receiving capecitabine at some line for treatment have significantly improved OS and 2) a prognostic model can classify patients into three risk groups associated with OS. InterpretationIn patients with HER2-negative LR/MBC, addition of capecitabine to paclitaxel and bevacizumab significantly improved PFS, ORR and response duration. This combination was reasonably well tolerated and may be considered of use as first-line treatment in rapidly progressive disease. FundingF. Hoffmann-La Roche Ltd, the Netherlands.

Plasma VEGF-a, angiopoietin-2 (ANG2) and soluble(s)TIE2 in patients (pts) with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X).

1072 Background: In the randomized phase II ATX trial, pts with HER2-negative LR/MBC were treated with first-line AT or ATX. We determined the prognostic value for outcome of VEGF-A, ANG2 and sTIE2 measured at baseline on cycle 1 day 1 (C1D1) and after cycle 1 (C2D1). Methods: 312 pts were randomized in 1:1 ratio to AT (T 90 mg/m2 on d1, 8, 15 and A 10 mg/kg on d1, 15 q4w x 6 cycles, followed by A 15 mg/kg on d1 q3w for next cycles) or ATX (T 90 mg/m2 on d1, 8, A 15 mg/kg on d1 and X 825 mg/m2bid on d1–14 q3w x 8 cycles, followed by the same dose of A and X q3w for next cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), response duration (RD), overall survival (OS) and safety. Plasma proteins on C1D1 (N = 173) and on C2D1 (N = 142) were measured by ELISA. The association of protein levels (continuous variable) with PFS and OS was evaluated by Cox proportional hazards model and Martingale residual plot. Results: At a median follow-up of 39 months (mo), there were 292 PFS events and 242 deaths. ATX significantly improved PFS as compared to AT (median 11 vs. 8.4 mo, stratified HR = 0.52; 95% CI, 0.41 – 0.67; P &lt; .001). The confirmed ORR in measurable disease (N = 268) was 67% in ATX vs. 50% in AT. Median RD was 6.4 mo (95% CI, 6.1 – 8.3) in ATX v 5.4 mo (95% CI, 5.1 – 6.0) in AT. Median OS was 24.1 mo in ATX vs. 23.1 mo in AT (P= .44). The aselected ‘biomarker’ cohort (N = 173) and overall trial cohort had similar baseline characteristics. ANG2 on C1D1 moderately correlated with sTIE2 on C1D1 (Pearson’s r = .44, P &lt; .001). High ANG2 on C1D1 was significantly associated with poor OS (HR = 1.6; 95% CI, 1.1 – 2.3; P = .01), but not with poor PFS (HR = 1.3; 95% CI, 1.0 – 1.3; P = .07). ANG2 on C2D1 was not significantly associated with OS (HR = 1.55; 95% CI, 0.99 – 2.4; P = .057) or with PFS (P= .6). sTIE2 and VEGF-A were not associated with outcome. All pts had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions: In HER2-negative LR/MBC, ATX is more effective (PFS, ORR and RD) than AT. A very high plasma level of ANG2 at baseline indicates a high risk for poor survival. Clinical trial information: NTR1348.

PD07-07: Combination of Paclitaxel and Bevacizumab without or with Capecitabine as First-Line Treatment of HER2−Negative Locally Recurrent or Metastatic Breast Cancer (LR/MBC): First Results from a Randomized, Multicenter, Open-Label, Phase II Study of the Dutch Breast Cancer Trialists' Group (BOOG).

Abstract Background: First-line treatment of HER2−negative LR/MBC with paclitaxel (T) and bevacizumab (A) has demonstrated improved progression-free survival (PFS) and overall response rate (ORR) when compared with T alone (E2100). We determined whether addition of capecitabine (X) to AT is safe and would be better effective than AT in women with HER2−negative LR/MBC. Methods: Eligibility criteria were age ≥18 &amp; ≤75 years, measurable or non-measurable HER2−negative LR/MBC, ECOG PS 0–1 and no prior chemotherapy for LR/MBC. Patients were randomized in 1:1 ratio to receive AT (4-week cycle of T 90 mg/m2 on days 1, 8, 15 and A 10 mg/kg on days 1, 15 for 6 cycles, followed by A 15 mg/kg on day 1 given 3-weekly for subsequent cycles) or ATX (3-week cycle of T 90 mg/m2 on days 1, 8, A 15 mg/kg on day 1 and X 825 mg/m2 bid on days 1–14 for 8 cycles, followed by A 15 mg/kg on day 1 and X 825 mg/m2 bid on days 1–14 given 3-weekly for subsequent cycles). Treatment was discontinued at disease progression, unmanageable toxicity or withdrawal of consent. The primary endpoint was PFS. Secondary endpoints were overall survival, ORR, duration of response and toxicity. Efficacy was evaluated according to RECIST 1.0 and toxicity was assessed according to NCI CTCAE 3.0. Results: From June 2007 till December 2010, 312 patients were recruited at 36 sites. The median age was 56 years (range 32–76). Among all patients, 52% had ECOG 0, 85% were hormone-receptor positive, 86% had measurable disease and 8% had bone-only metastases. These factors were well balanced between both arms. A total of 48% and 33% of patients, respectively, received prior hormonal therapy or radiotherapy for LR/MBC. At the data cut-off of 1st June 2011, the median follow-up duration was 23 months. 311 patients received at least one cycle of treatment and were evaluable for safety. The median number of treatment cycles in AT was 9 and in ATX was 11 (both 33 weeks). An ORR of ≥40% was reached in patients with measurable disease in both groups. The incidence of serious adverse events (SAEs) was 47% and 40% for AT and ATX, respectively, while that of treatment-related SAEs was 12% and 19%, respectively. Treatment-related deaths were 2% for AT and 2% for ATX. The overall rate of AEs grade 3 or 4 was similar in both arms as shown in Table 1, except for hand-foot syndrome grade 3 and neutropenia grade 3 in ATX. In addition, 6 patients with pulmonary embolism were reported in ATX. Conclusions: ATX was well tolerable, although more patients experienced hand-foot syndrome grade 3 and thromboembolic events than patients treated with AT. The efficacy data will be presented at the meeting. Support: This study was supported by Roche. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-07.

OT2-01-02: First-Line Bevacizumab in Combination with Capecitabine or Paclitaxel for HER2−Negative Locally Recurrent or Metastatic Breast Cancer (LR/MBC): A Randomized Phase III Trial.

Abstract Background A number of phase III studies have shown significant progression-free survival (PFS) benefits with the combination of bevacizumab (Bev) and either first-line capecitabine (X) or taxane therapy in LR/MBC. The ongoing open-label, randomized, phase III CECOG-sponsored TURANDOT study (CECOG/BC.1.3.005) is investigating the efficacy and safety of first-line Bev plus paclitaxel (P) versus Bev plus X in this setting. Materials and methods: Eligible patients (pts) are aged ≥18 years with HER2−negative, chemonaïve LR/MBC, an ECOG performance status of 0–2 and a life expectancy &amp;gt;12 weeks. Prior chemotherapy and concomitant hormonal therapy for LR/MBC are not permitted, but prior (neo)adjuvant chemotherapy is allowed if completed ≥6 months before randomization or ≥12 months if taxane based. Pts are randomized to receive Bev 10mg/kg days 1, 15 plus P 90mg/m2 days 1, 8, 15, q28d (Arm A) or Bev 15mg/kg day 1 plus X 1,000mg/m2 bid days 1–14, q21d (Arm B) until disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is to demonstrate non-inferiority in overall survival (OS) with Bev plus P versus Bev plus X (upper limit ≤1.33 for the two-sided confidence interval for hazard ratio [HR]). Secondary objectives are: comparison of overall response rate (RECIST criteria); PFS; time to response; duration of response; time to treatment failure; safety (CTCAE version 3); and quality of life (EORTC QLQ-30). The recruitment target is 560 pts. A sample size of 490 pts in the per-protocol population will be required to provide 80% power to reject the null hypothesis of inferiority at a one-sided significance level of 0.025, assuming a 24-month median OS with Bev plus P and an alternative hypothesis of HR=1. Data cut-off for adverse event reports was 12 Apr 2010. Interim and final efficacy analyses will be triggered after 175 and 389 events, respectively. Results: Recruitment to the study began in Sep 2008 and was completed in Aug 2010, with 561 pts randomized. Follow-up is ongoing. Conclusions: TURANDOT is the first study to examine the efficacy and safety of Bev plus P versus Bev plus X as first-line treatment for pts with LR/MBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-02.

A randomized, placebo-controlled phase II study of AMG 386 plus bevacizumab (Bev) and paclitaxel (P) or AMG 386 plus P as first-line therapy in patients (pts) with HER2-negative, locally recurrent or metastatic breast cancer (LR/MBC).

544 Background: AMG 386 is an investigational peptide-Fc fusion protein that inhibits angiogenesis by neutralizing the interaction between the Tie2 receptor and angiopoietin-1 and -2. We assessed t...

First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2251 patients

BackgroundFirst-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice. Patients and methodsPatients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point. ResultsMedian follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1–9.9). ConclusionsThe study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab–taxane therapy in this large study were consistent with results from randomised first-line trials.

Bevacizumab (Bev) combined with either capecitabine (X) or weekly paclitaxel (Pac) as first-line chemotherapy (CT) for HER2-negative, locally recurrent or metastatic breast cancer (LR/MBC): Preliminary safety data from the CECOG phase III TURANDOT trial.

1126 Background: The combination of Bev with first-line X or taxane-based therapy significantly improves progression-free survival (PFS) in LR/MBC. This phase III, randomized study is to determine the efficacy of Bev+Pac vs Bev+X in this setting. Methods: Patients with HER2-negative, chemonaïve LR/MBC and ECOG PS 0–2 are eligible. Prior (neo)adjuvant CT is permitted if completed ≥6 months before randomization (≥12 months for taxane-containing therapy). Pts are randomized to Bev+X (X 1,000mg/m2 bid d1–14 + Bev 15mg/kg d1, q21d) or Bev+Pac (Pac 90mg/m2 d1, 8, 15 + Bev 10mg/kg d1,15, q28d), with treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Primary endpoint is non-inferiority in overall survival with Bev+X vs Bev+Pac and recruitment target is 560 pts. This planned interim safety analysis includes pts randomized by July 31, 2009 who are eligible for the safety analysis (ie. post-baseline safety data available). Results: 174 pts have been randomized, 167 are eligible for analysis (median age 58 years [range: 31–77]): Bev+Pac n=87, Bev+X n=80. Most pts were postmenopausal (83%), with estrogen receptor-positive (77%) and progesterone receptor-positive (64%) disease, and ECOG PS 0 (71%); 50% had received prior adjuvant CT. 155 pts received ≥2 cycles of Bev therapy, as required per protocol. Median (range) number of 4-week Bev+Pac cycles administered was 4 (1–11) of Pac and 4 (1–12) of Bev. Median (range) number of 3-week Bev+X cycles administered was 6 (1–14) of X and 6.5 (1–14) of Bev. Adverse events (AEs) were observed in 82% and 80% of pts in the Bev+Pac and Bev+X groups, including grade ≥3 AEs in 32% and 31%, and serious AEs in 13% and 10%, respectively. The most frequent grade 3/4 AEs were neutropenia (13.8%) with Bev+Pac and diarrhea (8.8%) with Bev+X. Conclusions: With neutropenia and gastrointestinal disturbance representing the most frequent grade 3/4 AEs with Bev+Pac and Bev+X, respectively, preliminary safety data are in accordance with previously published safety data for these combinations and no safety concerns have been raised. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Roche Bristol-Myers Squibb, Roche Bristol-Myers Squibb, Roche

Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer

Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with anti-angiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0.4% in the single-arm study. There was a trend towards increased ONJ incidence in patients who received bisphosphonate therapy versus those with no bisphosphonate exposure (0.9 vs. 0.2%, respectively, in the pooled analysis of the randomised trials; 2.4 vs. 0%, respectively, in ATHENA). In conclusion, this is the largest analysis of ONJ in patients receiving bevacizumab for LR/MBC. The 0.3-0.4% incidence is considerably lower than previously suggested with anti-angiogenic therapy in a small retrospective analysis. The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management. The 0.9-2.4% incidence seen in bisphosphonate-exposed patients receiving bevacizumab is within the 1-6% range reported for bisphosphonates alone. Good oral hygiene, dental examination, and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of bevacizumab administration.

Analysis of Bevacizumab (Bev) Therapy, Bisphosphonate Use and Osteonecrosis of the Jaw (ONJ) in &amp;gt;1900 Patients Treated in Two Randomized, Controlled Trials.

Abstract Background: Long-term bisphosphonate therapy is known to increase the risk of ONJ. A 16% incidence of ONJ was reported in a retrospective analysis of 116 patients receiving bisphosphonates with anti-angiogenic therapy (Bev or sunitinib) for bone metastases from breast, colon, or renal cell cancers.Methods: To assess the incidence of ONJ with Bev, we analyzed data from &amp;gt;3500 patients with locally recurrent or metastatic breast cancer (LR/MBC) treated in three large trials of Bev-containing therapy: AVADO (Bev in combination with docetaxel); RIBBON-1 (Bev in combination with taxane, anthracycline-based combination therapy, or capecitabine); and MO19391 (single-arm safety study of &amp;gt;2000 patients receiving Bev-containing therapy in the general oncology practice context). The incidence of ONJ was compared in patients treated with Bev versus placebo and in patients with or without bisphosphonate exposure.Results: Data from the blinded phase of two randomized, placebo-controlled trials demonstrated an ONJ incidence of 0.3%. ONJ was more common in patients who also received bisphosphonate therapy than in those who received no bisphosphonates (Table). This observation is supported by data from 2216 patients treated in the single-arm MO19391 study (2.4% with bisphosphonate versus 0% without). AVADO*RIBBON-1**TotalIncidence of ONJ, no. of pts (%)Bev (n=492)Pla (n=238)Bev (n=817)Pla (n=412)Bev (n=1309)Pla (n=650)Overall population receiving Bev (n=1309)3 (0.6%)O1 (0.1%)O4 (0.3%)OBisphosphonate (n=233)1 (1.2%)O1 (0.6%)O2 (0.9%)ONo bisphosphonate (n=1076)2 (0.5%)OOO2 (0.2%)O *Bev 15 and 7.5 mg/kg arms pooled**Taxane/anthracycline and capecitabine cohorts pooledConclusions: This is the largest analysis of ONJ in patients receiving Bev for LR/MBC. The 0.3% incidence of ONJ with Bev is considerably lower than previously reported by Christodoulou et al. with anti-angiogenic therapy. As in the general population, the risk of ONJ is increased in patients exposed to bisphosphonates. The 0.9–2.4% incidence seen here in a large population of patients receiving Bev and bisphosphonate therapy is substantially lower than the 16% observed in a small cohort of patients from a retrospective analysis and within the range reported in the literature for bisphosphonates alone (1–4%). Good oral hygiene, dental examination and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of Bev treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 208.

5017 Multinational study (n = 2041) of first-line bevacizumab (Bev) plus taxane-based chemotherapy (CT) for locally recurrent or metastatic breast cancer (LR/mBC): updated results of MO19391

The selection of first-line chemotherapy for metastatic breast cancer (MBC) is complex because of the myriad of treatment options available and the inherent biologic heterogeneity of the disease. The potential treatment options are greatly influenced by estrogen and progesterone receptor and HER2 status of the tumor, and biopsy with reassessment of these markers at the time of disease recurrence is strongly recommended. Metastatic breast cancer is generally an incurable disease, with survival that could range from months to several years. Important but modest improvements in overall survival (OS) have been observed for women with MBC over the past few decades, in part because of improvements in systemic therapy. For women with endocrine-responsive disease, hormonal therapy is the appropriate initial treatment choice at the time of disease recurrence with rare exception. Initiation of systemic chemotherapy is appropriate for women with disease that is either hormone receptor negative, endocrine therapy refractory, or rapidly progressive with visceral involvement. The addition of trastuzumab to chemotherapy for women with HER2-positive breast cancer represents a clear standard of care. For HER2-negative MBC, sequential single-agent chemotherapy is preferred over combination therapy as a result of the more favorable toxicity profile and absence of a clinically significant improvement in survival with combination treatment. Many single-agent chemotherapeutic agents have activity in MBC, with most data supporting an anthracycline- or taxane-based approach. Bevacizumab in combination with chemotherapy prolongs progression-free survival in women with MBC, though its position in the first-line treatment of MBC relative to standard chemotherapy remains unclear at this time because of lack of OS benefit.

5058 Bevacizumab (Bev) combined with either capecitabine (X) or weekly paclitaxel (Pac) as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer (LR/MBC): the CECOG phase III TURANDOT trial

Analizar la formación de las enfermeras y la aplicación de las terapias complementarias (TC) en los cuidados de enfermería al paciente oncológico.El estudio se realizó en el hospital Duran i Reynals de l’Hospitalet de Llobregat, en las unidades de: hematología clínica, terapia intensiva, tratamiento programado, hospital de día, oncología médica, cuidados paliativos, consultas externas, soporte de la atención continuada, servicio de oncología radioterápica y en el equipo de soporte hospitalario.Estudio descriptivo transversal.Aplicación de un cuestionario elaborado que consta de dos apartados, uno de datos demográficos y otro apartado con 8 preguntas especificas.Enfermeras del área asistencial de todos los turnos que trabajen en las unidades mencionadas.Para el análisis de los datos se ha utilizado el paquete estadístico SPSS15.0 para Windows y se ha realizado un análisis descriptivo para todas las variables. Variables cualitativas: frecuencias y porcentajes. Variables cuantitativas: medidas de tendencia central y de dispersión.El 58,8% de las enfermeras ha realizado algún tipo de formación en TC. Las intervenciones mente-cuerpo son las más efectuadas en cuanto a formación, seguidas de las terapias manuales y las terapias de base energética. La relajación-visualización es la terapia que más aplican las enfermeras oncológicas.La formación de las enfermeras oncológicas en las TC es fundamental para poder informar y asesorar a sus pacientes y poder cuidarlos de una forma más holística. La falta de tiempo y de disposición del hospital al reconocimiento y valor de las TC son los principales factores de dificultad que se encuentran las enfermeras oncológicas.

Safety and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) for locally recurrent or metastatic breast cancer (LR/mBC): Analysis of MO19391 according to CT

1033 Background: Combination of B with first-line paclitaxel (TP) or docetaxel (TD) significantly improves PFS vs taxane alone in pts with LR/mBC. The open-label, multicenter MO19391 trial further assessed safety and efficacy of first-line B plus a taxane in &gt;2,000 pts in routine clinical practice. Methods: Eligible pts had HER2- negative LR/mBC (or HER2-positive LR/mBC progressing after trastuzumab-containing therapy), ECOG PS 0–2, no prior CT for LR/mBC and no evidence of CNS metastases. Pts received B 10mg/kg q2w or 15mg/kg q3w plus the physician's choice of taxane (TP or TD alone or with another CT) or other non-anthracycline CT according to physician's standard of care. Treatment was continued until disease progression, unacceptable toxicity, or refusal. The primary endpoint was safety (NCI CTCAE v3.0); secondary endpoints included TTP, OS, and safety in pts developing CNS metastases. Results: From Sept 2006 to June 2008, 2,027 pts from 37 countries were enrolled. Median follow-up is 7.4 months. CT included a taxane (alone or with CT) in ∼75% of pts. Non-taxane agents included capecitabine (X) and vinorelbine (V). In the overall population, median age was 54 years (range 21–93), 70% were ER and/or PgR positive, and 32% had disease-free interval (DFI) ≤24 months. Baseline characteristics were broadly similar across subgroups. However, the X monotherapy subgroup included fewer pts with &gt;3 metastatic lesions and more with a DFI ≤24 months and/or triple-negative disease compared with other subgroups. Safety and efficacy results grouped by CT are shown below. OS data are still immature (85% of pts alive at this analysis). Conclusions: In this large phase IV study, safety and efficacy of B plus TP or TD was similar to results of E2100 and AVADO. Variations in toxicities were consistent with the known profiles of each CT and no new safety signals for B were observed. The lowest incidences of serious Aes were seen with B plus TP or X. TTP was shorter with X and non-taxane combinations. Such findings are potentially attributable to small pt numbers and differences in baseline characteristics. These results show that B can be safely and effectively combined with a wide range of commonly used CT regimens as first-line therapy for mBC. [Table: see text] [Table: see text]