Clinical significance of circulating tumor cells (CTCs) in hormone receptor-positive (HR+) metastatic breast cancer (MBC) patients (pts) receiving letrozole (Let) or Let plus bevacizumab (Bev): CALGB 40503 (Alliance).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1049-1049
Author(s):  
Mark Jesus Mendoza Magbanua ◽  
Oleksandr Oleksandr Savenkov ◽  
Erik Asmus ◽  
Karla V. Ballman ◽  
Janet H Scott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Value ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy ◽  
Study Results

1049 Background: CALGB 40503 randomized HR+ MBC postmenopausal pts to Let alone or Let+Bev as first-line therapy. Adding Bev to Let prolonged progression-free survival (PFS) but not overall survival (OS) (Dickler JCO 2016). We performed a correlative study to assess prognostic and predictive value of CTCs in this population. Methods: Blood was collected prior to initiation of treatment. CTCs were enumerated using US FDA-cleared CellSearch assay; samples with ≥5 CTCs per 7.5 mLs of blood were considered CTC-positive (CTC+). Correlation of CTCs with PFS and OS was assessed using Cox regression analysis. Median follow-up was 39 months (mo). Results: Of 343 pts treated, 294 had CTC data and were included in this analysis. Original study results that showed improved PFS (HR = 0.75; 95% CI: 0.59-0.96) but not OS (HR = 0.87; 95% CI: 0.65-1.18) in pts receiving Let+Bev compared to Let were recapitulated in this subset. In multivariable analysis, CTC+ pts (31%) had significantly reduced PFS (HR = 1.49; 95% CI: 1.12-1.97) and OS (HR = 2.08; 95% CI: 1.49-2.93) compared to CTC- pts. Moreover, CTC+ pts who did not receive Bev had worse PFS (HR = 2.31; 95% CI: 1.54-3.47) and OS (HR = 2.64; 95% CI: 1.59-4.40) (Table). CTC+ pts who received Bev had numerically longer median PFS (18.0 vs. 7.0 mo) and OS (33.6 vs. 27.1 mo) compared to CTC+ pts with no Bev; however, tests for interaction between CTC status and Bev (yes vs. no) were not statistically significant for PFS (p=0.70) or OS (p=0.84). Conclusions: CTCs were highly prognostic in this study involving addition of Bev to first-line Let in postmenopausal HR+ MBC. Further research to determine the potential predictive value of CTCs in the setting of both metastatic disease and early breast cancer is warranted. Support: U10CA180821, U10CA180882; Genentech; https://acknowledgments.alliancefound.org ; NCT00601900. Survival in HR+ MBC pts receiving Let or Let+Bev stratified by CTC status. Clinical trial information: NCT00601900. [Table: see text]

scholarly journals Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1980-1986 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Tomasz Burzykowski ◽  
Marc Buyse ◽  
George Sledge ◽  
James Carmichael ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Rates ◽  
First Line ◽  
First Line Therapy ◽  
Hazard Ratios

Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

scholarly journals The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer

2020 ◽  
Vol 27 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Xinyue Wang ◽  
Xiwen Bi ◽  
Zhangzan Huang ◽  
Jiajia Huang ◽  
Wen Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Metastatic Breast Cancer ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Independent Prognostic Factor ◽  
First Line ◽  
Cox Regression Analysis

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.

Non-Pegylated Liposomal Doxorubicin in Combination with Cyclophosphamide or Docetaxel as First-Line Therapy in Metastatic Breast Cancer: A Retrospective Analysis

2009 ◽  
Vol 95 (4) ◽  
pp. 422-426 ◽  
Author(s):  
Lorenzo Livi ◽  
Icro Meattini ◽  
Carla De Luca Cardillo ◽  
Monica Mangoni ◽  
Daniela Greto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Retrospective Analysis ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Aims and background Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer. Methods Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria. Results The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1–2 leucopenia, alopecia, nausea and vomiting; no grade 3–4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity. Conclusions Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

scholarly journals Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance)

2015 ◽  
Vol 33 (21) ◽  
pp. 2361-2369 ◽  
Author(s):  
Hope S. Rugo ◽  
William T. Barry ◽  
Alvaro Moreno-Aspitia ◽  
Alan P. Lyss ◽  
Constance Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Nonhematologic Toxicity

Purpose We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. Patients and Methods Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m2 (arm A), nab-paclitaxel 150 mg/m2 (arm B), or ixabepilone 16 mg/m2 (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. Results In all, 799 patients were enrolled, and 783 received treatment (97% received bevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. Conclusion In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.

scholarly journals Salvage therapies for radiation-relapsed IDH-mutant astrocytoma and 1p/19q codeleted oligodendroglioma

2021 ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Milan G Chheda ◽  
Tanner M Johanns ◽  
...  
Keyword(s):  
Cox Regression ◽  
Salvage Surgery ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Tertiary Cancer Center

Abstract Background Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. Methods Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or non-alkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. Results Recurrent Oligo (n=35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = 0.002) and OS (median: 6.3 vs 1.5 years, respectively, P &lt; 0.001) than Astro (n=59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure &gt;2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro. Conclusions Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.

Assessment of multiple endocrine therapies for metastatic breast cancer in a multicenter national observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1052-1052 ◽  
Author(s):  
Olivia Le Saux ◽  
Audrey Lardy-Cleaud ◽  
Sophie Frank ◽  
Paul H. Cottu ◽  
Barbara Pistilli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real Life ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Large Populations ◽  
Visceral Disease

1052 Background: For HR+/HER2– metastatic breast cancer (mBC), International guidelines recommend multiple lines of endocrine therapy (ET) before starting chemotherapy. Few studies have assessed the efficacy of such strategy on large populations. Our objective was to evaluate multiple ET activity according to clinical and biological characteristics and type of ET. Methods: All patients (pts) who initiated treatment for a newly diagnosed mBC between January 2008 and December 2014 in all 18 French Comprehensive Cancer Centers were included in the real life ESME database. ESME collects retrospective data using a clinical trial-like methodology. Database lock was 8 Dec 2016. Primary endpoint of the current study was progression free survival (PFS) on successive ET lines. Only pts with ET alone were assessed (pts receiving ET after chemotherapy as maintenance therapy, or combined with targeted treatment were excluded). Results: 9921 pts out of 16703 in ESME, had HR+/HER2- mBC (median age 62.0 years[range 23-96]). 53.9% of pts had visceral and 80.1% non visceral disease at diagnosis. Median OS of HR+/HER2- pts was 42.15 months (95% CI, 40.93-43.27). As first-line therapy, 4123 pts (41.6%) received ET alone, while 2038 received chemotherapy alone (20.5%) and 3667 received both (37%). Median PFS for first-line ET (N=4123) was 11.3 months (95% CI, 10.6-11.9). Only 668 pts (16%) received subsequent lines of ET alone. Types of ET used are described in the table below. Successive PFS will be reported at the meeting. Conclusions: Those data show that ET is prescribed to less than 50% of patients with HR+/HER2- mBC in first line and only to a small minority in subsequent lines. This is not in line with existing guidelines (NCCN, ABC3). Real-life median PFS for first-line ET is consistent with median PFS reported in clinical trials (Nabholtz, 2000). [Table: see text]

Real-life results from the prospective QoliXane trial of the platform for outcome, quality of life, and translational research on pancreatic cancer (PARAGON) registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4625-4625
Author(s):  
Salah-Eddin Al-Batran ◽  
Ralf Dieter Hofheinz ◽  
Alexander Reichart ◽  
Claudia Pauligk ◽  
Rudolf Schlag ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pancreatic Cancer ◽  
Cox Regression ◽  
Real Life ◽  
Progression Free Survival ◽  
Response Analysis ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy

4625 Background: Gemcitabine and nab-paclitaxel (NPG) is standard first-line therapy for metastatic pancreatic cancer (mPC), but the pivotal study did not include quality of life (QoL) analyses. Methods: The QOLIXANE-PARAGON study started as a prospective, non-interventional, multicenter study conducted in Germany and transitioned into a permanent registry for pancreatic cancer patients (pts) considering all types of treatments. This report focuses on the pts enrolled into the QOLIXANE portion of the study. Pts were recruited from 95 German centers. QoL was prospectively measured via EORTC-C30 questionnaires (prior to and every month thereafter): therapy and efficacy parameters were prospectively collected. QoL and efficacy endpoints were analyzed in the intention-to-treat population (ITT). The primary endpoint was the rate of pts without deterioration of QoL/Global Health Score (QoL/GHS) at 3 months. Results: 600 pts were enrolled. Mean GHS/QoL score at baseline was low and was 46.2 (SD 22.8). Median progression-free survival was 5.85 months (95% CI, 5.23 to 6.25). Median overall survival (OS) was 8.91 months (95% CI, 7.89 to 10.19). The KM-analysis showed that 61% and 41% of pts had maintained QoL/GHS after 3 and 6 months, respectively. Median time to deterioration of QoL/GHS was 4.68 months (95% CI, 4.04 to 5.59). Mean QoL/GHS improved from 46.1 (SD 22.7) at baseline to 52.8 (SD 21.3) after 6 months. In the QoL response analysis, 34.6%, 37.4% and 28% of evaluable pts had improved, stable and worse QoL/GHS after 3 months, respectively. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a HR of 0.86 (p < 0.0001). Conclusions: QoliXane the largest study on QoL of mPC. It shows that time to deterioration of QoL is short but that a relevant group of mPC in first line have improved or maintained QoL after 3 and 6 months and that QoL is a predictor of pts outcome. Clinical trial information: NCT02691052 .

Bevacizumab associated calcifications might be a prognostic marker in patients with metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16108-e16108
Author(s):  
Yuwen Zhou ◽  
Qiu Meng
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Prognostic Marker ◽  
Cox Regression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Therapy

e16108 Background: Cetuximab associated calcifications is a positive predictive factor in metastatic colorectal cancer (mCRC). In patients with glioblastoma, bevacizumab-induced calcifications are also related to a better prognosis. However, tumor calcifications are rarely recognized in mCRC patients treated with bevacizumab. This study was to investigate the correlation between clinical outcome and calcification in mCRC who received bevacizumab and chemotherapy as the first-line treatment. Methods: A single retrospective cohort study was conducted with all diagnosed mCRC cases who received bevacizumab and chemotherapy as the first-line therapy in our hospital from January 2016 to January 2019. Clinical variables were retrieved from medical records and tumor calcification were evaluated independently by radiologists on the basis of computed tomography scans. A univariate and multivariate COX regression analysis was performed to evaluate the association between calcification and outcome. Results: 159 patients with an average age of 59.0 years were included. Median follow-up was 29.6 months. Among all enrolled patients, 31 had tumor calcification [31/159 (19.5%)]. The median overall survival (OS) and progression-free survival (PFS) was significantly better in patients with calcification than those without calcification (28.0 vs. 24.9 months, p= 0.024; 12.0 vs. 10.0 months, p= 0.026). A higher objective response rate (61.3% vs. 50.0%) was also observed in calcification group. On multivariate analysis, tumor calcification was independently associated with OS (hazard ratio 1.799, 95% CI 1.002–3.230) and PFS (hazard ratio 1.609, 95% CI 1.013–2.557). Conclusions: Tumor calcification was independently associated with improved prognosis in colorectal cancer. It might be a potential prognostic marker.

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