Paclitaxel In Metastatic Breast Cancer Research Articles

Abstract P4-07-54: Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors

Abstract Background: Advances in screening and treatment have led to increase in breast cancer (BC) survival in recent years but prognoses for metastatic BC remain poor with poorer outcomes as health-related quality of life (HRQOL). Treatment as bevacizumab and paclitaxel for metastatic BC, although that can increase time to progression of disease, often carry toxicity and is not curative but rather palliative in intent with the goal to improve or maintain HRQOL. The aim of this work was to assess impact of clinical factors such as disease progression, toxicity on HRQOL. Methods: COMET study is a multicenter prospective single-arm cohort study in France whose main objective was to identify biological factor that could predict the clinical benefit of bevacizumab-paclitaxel combination therapy as first treatment in HER2 negative metastatic BC. HRQOL was assessed at baseline, at every cycle (every for 4 weeks) until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its BC specific module, the EORTC QLQ-BR23. In this ancillary study, we targeted 5 dimensions HRQOL for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). The primary endpoint was time until definitive deterioration (TUDD) in HRQOL scales that defined as time between inclusion and the first decrease HRQOL score ≥ 5 points compared to baseline score, with no further improvement of at least 5 points. Multivariable Cox model with time dependent covariate was performed to assess clinical factors associated with TUDD for each of the 5 target dimensions HRQOL. We performed 3 models for each dimension: model 1 including all covariate with p< 0.10 in univariable; model 2 including model 1 and adjusted on cancer subtype and model 3 included model 1 stratified by cancer subtype. P value < 0.01 were considered statistically significant. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. Median age at inclusion was 58 years (range: 29-83), and 24.4% of patients had triple negative tumor subtype. About 79 % of cancers were invasive ductal carcinoma and 43 % patients had least 3 metastasis sites at baseline. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. In multivariable analyses, Disease Progression was associated with TUDD of GHS (HR [99%CI] =2.4 [1.2-4.9] and TUDD of PF (2.1 [1.1-3.7]). After adjusted on cancer subtype, association persisted with TUDD of GHS (p=0.009). Performance Status was associated with TUDD of PF (1.6 [1.2-2.3]), and TUDD of Pain (1.6 [1.1-2.3]). Performance Status association with TUDD of PF continued after adjustment on cancer subtype (p=0.0003). Prior endocrine therapy was associated with TUDD of pain in patients with tumor with positive hormone receptor (HR+) (2.4 [1.2-4.7]). There was no factor associated with TUDD of EF and TUDD of FA. Conclusion: Results of this study have shown that among the 5 targeted dimensions HRQOL, Physical Functioning was deteriorated in the shortest time. Disease progression, base line performance status and prior endocrine therapy for HR+ subtype, are clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Oumar Billa, Sandrine Dabakuyo, Marion Chevrier, Franck Bonnetain, Isabelle Desmoulins, William Jacot, Olivier Trédan, Marc Debled, Christelle Levy, Anthony Gonçalves, Jean-Marc Ferrero, Florence Dalenc, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Mireille Mousseau, Julien Grenier, Jean-Philippe Jacquin, Fatima-Zohra Toumi, Frédérique Berger, Jérôme Lemonnier, Jean-Yves Pierga. Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-54.

Cost of home vs clinic administration of paclitaxel in metastatic breast cancer

To estimate the costs associated with home administration of oral paclitaxel and encequidar (novel P-glycoprotein pump inhibitor allowing oral paclitaxel bioavailability) compared with clinic/office administration of intravenous (IV) paclitaxel (175 mg/m2) and protein-bound paclitaxel in US patients with metastatic breast cancer. Economic analysis. A cost calculator was constructed from a payer's perspective including all costs related to administration of the chemotherapies, including drug administration, premedications and concomitant medications, oncologist office visits, laboratory testing, and administration-related adverse events. Total administration cost per patient per month (PPPM) and 6-month costs per patient were estimated for oral paclitaxel and encequidar, 175 mg/m2 IV paclitaxel, and protein-bound paclitaxel. Three scenarios for oral paclitaxel and encequidar, a weekly IV paclitaxel scenario (80-100 mg/m2), and univariate sensitivity analyses were conducted. Home administration of oral paclitaxel and encequidar was associated with a total administration cost of $523 PPPM, 64.4% lower than once-every-3-weeks IV paclitaxel (175 mg/m2; $1469 PPPM) and 63.8% lower than protein-bound paclitaxel (260 mg/m2; $1445 PPPM). Difference in costs was driven largely by higher administration and premedication costs associated with IV therapies. Scenario analyses showed that increased clinical experience with home administration of oral paclitaxel and encequidar was associated with reduction in cost of care associated with its administration over time. For the weekly IV (80-100 mg/m2) paclitaxel scenario, the total administration cost was $2510 PPPM (4.8 times higher than for oral paclitaxel and encequidar). Univariate sensitivity analysis demonstrated that the model findings were robust. Home administration of oral paclitaxel and encequidar was associated with lower administration costs compared with once-every-3-weeks IV paclitaxel (175 mg/m2) and protein-bound paclitaxel, resulting in potential cost savings for payers.

Macular oedema associated with taxanes: A case report and literature review

Abstract Background and purpose Although taxanes are a frequently used group of chemotherapy agents, they can, rarely, lead to macular oedema. The purpose of this article is to review and communicate, in an integrated way, the data of the cases previously reported in the literature, as well as to present a new case. Material and methods Narrative review of reports of cases of macular oedema associated with taxanes, and communication of the clinical case of a 73-year-old woman who, after treatment with paclitaxel for metastatic breast cancer, developed macular oedema that disappeared after discontinuing the drug. Results The review included 57 cases with data from 109 eyes collected in 52 articles. The large majority (76.79%) of the cases were women, and the mean age was 58.75 years. The cancer that most frequently motivated the treatment was breast cancer (60.72%), and 92.5% of cases had metastases. The most frequently associated drug was paclitaxel (52.63%). The median time to symptom development was 4.25 months. At the initial examination, 92.86% of the cases had bilateral oedema and the mean visual acuity was 0.4 (decimal scale). The mean macular thickness was 509.63 microns, and 97.83% of the eyes had no or minimal angiographic findings. In 90.57% of the cases, the treatment with taxanes was interrupted, and some other treatment was used in 43.86% of the cases, with the most widely used being acetazolamide. The outcome was favourable, to a greater or lesser extent, in 96.23% of cases. Conclusions Despite being a rare entity, macular oedema associated with the use of taxanes is a disorder that every oncologist and ophthalmologist should be aware of, taking into account the good outcome of the condition that usually occurs when treatment is suspended.

Abstract P2-15-04: Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study)

Abstract OBJECTIVE: Nab-paclitaxel (nab-PTX) has superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), but chemotherapy-induced peripheral neuropathy (CIPN) is more frequent with nab-PTX. In a single arm phase 2 trial (CA002-0LD), low dose nab-PTX (175 mg/m2) every 3 weeks (q3w) resulted in a good objective response rate (39.5%) without CIPN of grade 3 or higher. Therefore, we conducted a randomized controlled study to evaluate the optimal dose of nab-PTX by comparing a low dose (LD) and a medium dose (MD) to the standard dose (SD). Here, we evaluate the patients-reported outcomes (PROs) and health-related quality of life (HRQoL) in the ABROAD study. PATIENTS AND METHODS: Three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) were administered in patients with HER2-negative metastatic breast cancer. The primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates with the three doses were estimated by logistic regression. The optimal dose was selected by 2-step selection. First, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was dropped. Then, a dose with an estimated incidence of grade 3/4 neurotoxicity >10% was also dropped. PROs and HRQoL were assessed as secondary endpoints at baseline, and during the 2nd, 4th and 6th courses of protocol treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Patient Neurotoxicity Questionnaire (PNQ), Cancer Fatigue Scale (CFS) and EuroQol 5 Dimension (EQ-5D). The primary outcome for PROs and HRQoL was the FACT-Taxane trial outcome index (TOI), and inter-group comparison was performed using a mixed effect model for repeated measures (MMRM). This trial was registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429). RESULTS: A total of 141 patients were randomly assigned to SD (n=47), MD (n=46) or LD (n=48) nab-PTX. PFS analysis showed that LD nab-PTX at 180 mg/m2/3 weeks was the optimal dose with good clinical efficacy and tolerability for patients with MBC (reported by Hara at ASCO2019). Longitudinal analysis (MMRM) showed that the difference from the baseline FACT-Taxane TOI score at MD and LD were significantly better than that at SD (MD vs. SD p<0.001, LD vs. SD p<0.001). Differences from baseline for the FACT-Taxane total score, physical well-being sub-score, and emotional well-being sub-score at MD and LD were also better than at SD. The difference from baseline for the CFS score at LD was better than that at SD (p=0.013) and those for EQ-5D utility scores at MD and LD were better than that at SD (MD vs. SD p=0.011, LD vs. SD p<0.001). There were no significant differences for the PNQ. CONCLUSION: Our results show that low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose for PFS and from the perspectives of PROs and HRQoL. Citation Format: Hiroaki Kato, Fumikata Hara, Masahiro Kitada, Masato Takahashi, Yuichiro Kikawa Yuichiro Kikawa, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Junji Tsurutani, Naruto Taira, Tsutomu Takashima, Kosuke Kashiwabara, Tomohiko Aihara Tomohiko Aihara, Hirofumi Mukai. Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-04.

Randomized, optimal dose-finding, phase II study of tri-weekly nab-paclitaxel in patients with metastatic breast cancer (ABROAD).

1070 Background: Although nab-paclitaxel (nab-PTX) has shown superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), chemotherapy induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In a single arm Phase 2 trail (CA002-0LD), low dose nab-PTX (175mg/m2) every 3 weeks (q3w) demonstrated a good objective response rate (39.5%) without grade 3 or higher CIPN. Herein, we conducted multicenter randomized controlled study to evaluate optimal dose of nab-PTX comparing lower dose (LD or MD) to standard dose (SD). Methods: This study compared three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) in patients with HER2 negative metastatic breast cancer. Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses are estimated by the logistic regression. Optimal dose was selected by 2 step selection. At first, if hazard ratio (HR) for PFS was less than 0.75 or more than 1.33, the inferior dose was dropped. Then, if estimated incidence rate of grade 3/4 neurotoxicity exceed10%, that dose was also dropped. This trial is registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429). Results: In this study, 141 patients were randomly assigned to SD (n = 47), MD (n = 46) or LD (n = 48). Median PFS was 6.66 vs 7.34 vs 6.82 months, respectively. HR was 0.73 (95% confidence interval (CI): 0.42-1.28) in MD vs SD. SD was dropped due to inferiority to MD. HR was 0.77 (95%CI 0.47-1.28) in LD vs SD, and 0.96 (95%CI 0.56-1.66) in LD vs MD. LD and MD were carried over to next step due to equivalence. Overall survival was not different among all dose arms. Rate of dose reduction by treatment course was significantly higher in SD arm. Estimated incidence of grade 3/4 neurotoxicity rate was 29.5% in SD, 14.0% in MD and 5.9% in LD. Final selected dose was LD 180mg/m2. HR-QOL results will be presented. Conclusions: Low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose with good clinical efficacy and tolerability for patients with MBC. Clinical trial information: C000012429.

EFFICACY AND SAFETY OF NANOPARTICLE ALBUMIN-BOUND PACLITAXEL VERSUS PACLITAXEL IN METASTATIC BREAST CANCER

Purpose: To compare the efficacy and safety of nab-pacitaxel versus paclitaxel in patients with metastatic breast cancer. Patients and Methods: A total of 92 patients with metastatic breast cancer received chemotherapy for nab-palitaxel versus paclitaxel at the dose of 260mg/m2 and 175mg/m2 respectively for total 8 cycles at the Hospital of Hue University of Medicine and Pharmacy and of Hue Central Hospital from February 2013 to October 2015. Results: The mean age in two groups of patients is 54 and 53 years old. The ECOG index was 0-1 in both groups. Menopausal status accounted for 73% in 2 groups. Dominant metastatic organ sites of two groups are bone, lung, liver. Multiple sites of metastasis in nab-paclitaxel and paclitaxel groups were 18% and 20%, respectively. The response rate of patients with nab-paclitaxel was 54.5% versus 31.2% in the paclitaxel group, p = 0.024. The time to progression was 8.46 months in the nab-paclitaxel group and 7.38 months in the paclitaxel group, p = 0.019. The median survival time of the nab-paclitaxel and paclitaxel groups was 28.89 and 27.79 months, respectively, p = 0.554. Neutropenia rates in the nab-pacitaxel and paclitaxel groups were 27.3% and 39.6% respectively, p = 0.033. Other toxicities were similar in both groups. Conclusion: Nab-Paclitaxel has clinical benefits over paclitaxel in metastatic breast cancer because of higher response rate, prolonged time to progression and less neutropenia. Key words: metastatic breast cancer, nab-paclitaxel, paclitaxel

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.

First-line bevacizumab in combination with weekly paclitaxel for metastatic breast cancer: efficacy and safety results from a routine oncology practice analysis

Background: First-line bevacizumab plus paclitaxel therapy for human epidermal growth receptor factor 2 negative (HER2-) metastatic breast cancer (MBC) demonstrated a median progression-free survival (PFS) of around 11 months in few pivotal randomized phase 3 trials (E2100, TURANDOT, and CALGB 40502). However median overall survival (OS) did not significantly differ between treatment arms. Patients and methods: We analysed a series of MBC patients treated between 2008 and 2016 at our Department using bevacizumab plus paclitaxel regimen as first line (bevacizumab 10 mg/kg on days 1,15 q28 plus paclitaxel 90 mg/mq on days 1,8,15 q28). Primary endpoints were efficacy outcomes measured as PFS, overall response rate (ORR), clinical benefit rate (CBR), and OS on the whole series, and on selected subgroup of patients. CBR was defined as the percentage of patients who have achieved complete response, partial response or stable disease > =6 months. Toxicity profile of the treatment was recorded following the NCI CTCAE, version 4. Results: We overall evaluated a series of 97 patients. The median PFS was 9 months (range 2-68); no significant differences were shown in patients previously treated with taxanes in (neo)adjuvant setting (p = 0.42), and endocrine treatment for the MBC (p = 0.53). The best ORR was 25% (24/96 cases), and the CBR was 72.9% (70/96 cases). No significant difference emerged in terms of presence of visceral disease (9 vs 19 months; HR 1.1 95%CI 0.67 to 1.9; p = 0.63), triple negative (8 vs 13 months; HR 1.5 95%CI 0.74 to 4.67; p = 0.19), age (<65 vs > =65 years; p = 0.25), and time to failure from adjuvant treatment ( < =18 vs > 18 months; p = 0.12). The median OS was 26 months (range 2-111). Patients showing a PFS longer than 18 months evidenced a significant OS improvement (21 vs 75 months; p < 0.0001). Eleven grade 3 AE were reported: hypertension (5.1%), neutropenia (5.1%), and peripheral neuropathy (1%). Conclusions: In our experience bevacizumab plus paclitaxel regimen as first line chemotherapy for HER2- MBC confirmed the efficacy results of pivotal trials. The regimen is highly effective and overall well-tolerated. Patients with prolonged PFS (>18 months) resulted in a significant better OS. Therefore, there is a strong need for studies aiming to identify predictive factors for response to treatment.

Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study.

Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum-taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS). We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007-2016 with the combination of carboplatin AUC 2 plus paclitaxel 80mg/m2, both given on days 1 and 8 in every 21-day cycle. 264 patients were evaluable for treatment safety and activity. The objective response rate (ORR) was 44.7%. Median PFS and OS were 8.6 and 23.7months, respectively. Triple-negative breast cancer (TNBC) patients had significantly lower PFS and OS times compared to other biology groups. At multivariable analysis, previous exposure to taxanes, HR-positive HER2-negative biology, a higher number of metastatic sites, and de novo metastatic disease at diagnosis were associated with reduced PFS, while receiving maintenance therapy correlated with improved PFS. Overall, the treatment was quite well tolerated, with 10.2% of patients discontinuing one or both drugs because of adverse events (AEs). G3-G4 neutropenia occurred in 16.8% of patients, while the incidence of febrile neutropenia was 2.3%. Weekly carboplatin-paclitaxel regimen is active and well tolerated in mBC treatment. Prospective studies should be conducted to compare its efficacy and tolerability with standard single-agent paclitaxel or docetaxel treatment schedules, as well as with more recent combination regimens.

Safety and antitumor activity of weekly carboplatin plus paclitaxel in metastatic breast cancer: A ten years, single-institution, retrospective analysis.

e12556 Background: Safety and activity of weekly carboplatin plus paclitaxel in patients (pts) with metastatic breast cancer (mBC) are poorly known. Nevertheless, taxane-based chemotherapy (ChT) is the milestone in mBC treatment. In this retrospective analysis, we report the safety and clinical activity of this combination in a consecutive series of pts treated at IRCCS Fondazione Istituto Nazionale dei Tumori in Milan in the last decade. Methods: We collecteddata on mBC patients treated between January 2007 and December 2016 with carboplatin AUC 2 plus paclitaxel 80 mg/m2on days 1 and 8, every three weeks. Selection criteria were: ECOG 0-1; evaluable and/or measurable mBC; known estrogen and progesterone receptors (ER/PgR) status and HER2 expression levels. 274 pts fulfilled the selection criteria, and 265 pts were evaluable for response and survival. Response was assessed according to RECIST criteria. Results: The median number of administered cycles was 6 (range 1-17). 66.4% and 88.3% of pts had received taxanes or antracyclines, respectively, as an adjuvant treatment or in the metastatic setting. 97% of HER2+ pts received trastuzumab concomitant with ChT. Among patients with ER/PgR-positive tumors, 42.8% received different endocrine treatments as maintenance therapy after achieving the best response with ChT or due inacceptable toxicity. Hematological and gastrointestinal toxicities were the most frequent adverse events (AEs), and were severe in 19% and 1.2% of pts, respectively. In particular, G3-G4 neutropenia and febrile neutropenia occurred in 16.8 % and 1.9 % of pts, respectively. 10.2% of pts discontinued the treatment because of toxicity. The objective response rate was 44.8% in the overall population, with median progression free survival (mPFS) of 8.6 months and median overall survival (mOS) of 23.7 months. Conclusions: Weekly carboplatin plus paclitaxel is a well-tolerated and active regimen across all different molecular subgroups of mBC. [Table: see text]

Can we efficiently and safely combine a pan-class I phosphatidylinositol-3-kinase inhibitor with paclitaxel in metastatic breast cancer?

Despite all therapeutic advances, patients with advanced and metastatic breast cancer (MBC) remain incurable in most cases. The majority of these patients progress after one to two years on first line systemic chemotherapy or endocrine therapy (1,2). Hence, there is a crucial need for more efficient and less toxic therapies in the first line setting and beyond to delay the time to progression and to improve outcomes.

Can we efficiently and safely combine a pan-class I phosphatidylinositol-3-kinase inhibitor with paclitaxel in metastatic breast cancer?

Can we efficiently and safely combine a pan-class I phosphatidylinositol-3-kinase inhibitor with paclitaxel in metastatic breast cancer?

Nab-paclitaxel, docetaxel, or solvent-based paclitaxel in metastatic breast cancer: a cost-utility analysis from a Chinese health care perspective.

BackgroundPaclitaxel and docetaxel are commonly used for metastatic breast cancer in the People’s Republic of China. To improve the safety and efficacy of paclitaxel, an albumin-bound formulation (nab) is now available in the People’s Republic of China (Abraxane®). To provide health economic data for the key stakeholders, a cost-utility analysis comparing nab-paclitaxel to docetaxel, both as alternatives to paclitaxel, was conducted.MethodsA meta-analysis of clinical outcomes Phase III trials comparing nab-paclitaxel (260 mg/m2 every [q] 3 weeks) or branded docetaxel (100 mg/m2 q 3 weeks), to solvent-based branded paclitaxel (175 mg/m2 q 3 weeks) was undertaken to provide safety and clinical data. Resource use data for the delivery of anticancer therapy and for the treatment of grade 3/4 toxicity was collected from a time and motion study conducted in three Chinese cancer centers and from a survey of clinicians. Using the Time Trade-Off technique, health utility estimates were derived from interviewing 28 breast cancer patients from one cancer center in the People’s Republic of China. All costs were reported in 2014 US dollars.ResultsNab-paclitaxel had the most favorable safety profile, characterized with the lowest incidence of grade 3/4 neutropenia, febrile neutropenia, anemia, and stomatitis. When the median number of cycles delivered from the clinical trials was applied, nab-paclitaxel had a cost per course of $19,752 compared with $8,940 and $13,741 for paclitaxel and docetaxel, respectively. As an alternative to paclitaxel, the cost per quality-adjusted life-year (QALY) gained with nab-paclitaxel suggested better value than with docetaxel ($57,900 vs $130,600).ConclusionNab-paclitaxel appears to be a cost-effective option compared with docetaxel and paclitaxel, for metastatic breast cancer in the People’s Republic of China.

Abstract P1-10-05: A cost utility analysis from a Chinese health care perspective of Nab-paclitaxel or docetaxel, both as alternatives to solvent-based paclitaxel in metastatic breast cancer (MBC)

Abstract Background: Paclitaxel and docetaxel are commonly used for the treatment of MBC in China. However, one important drawback, particularly with docetaxel, is the potential for dose-limiting toxicity. To improve the side effect profile and efficacy of paclitaxel, an albumin-bound formulation (nab-paclitaxel) is currently available in China (Abraxane®). To provide health economic data for China, a cost utility analysis comparing nab-paclitaxel to docetaxel, both as alternatives to paclitaxel was conducted. Methods: Clinical data was obtained from a meta analysis of randomized trials comparing either nab-paclitaxel (260 mg/m2 q3wk) or branded docetaxel (100 mg/m2 q3wk) to solvent-based branded paclitaxel (175 mg/m2 q3wk). Health care resource use for the delivery of chemotherapy and the management of grade 3/4 toxicity was collected from a time and motion study in three Chinese cancer centers, from a survey of clinicians and from the oncology literature. Using the Time Trade-off technique, treatment preferences and utility estimates were obtained from interviewing 28 cancer patients from two centres in China. All costs were reported in 2014 $U.S. Results: Nab-paclitaxel had the most favourable safety profile characterized with the lowest incidence of grade 3/4 neutropenia, febrile neutropenia, anemia, emesis and stomatitis. This translated to lower costs for managing the grade 3/4 side effects of nab-paclitaxel relative to both docetaxel and paclitaxel ($21 vs. $166 vs. $81) In the preference assessment, 22 of 28 (78.6%) patients selected nab-paclitaxel as their preferred agent. As an alternative to paclitaxel, the incremental cost per quality adjusted life year (QALY) gained was determined to be more favourable with nab-paclitaxel than docetaxel ($57,900 vs. $130,600). Conclusions: Nab-paclitaxel is an economically attractive alternative to both paclitaxel and docetaxel in MBC patients, providing a substantially lower cost per QALY. Additionally in the patient preference survey, the majority of patients surveyed selected nab-paclitaxel as their preferred agent. Citation Format: George Dranitsaris, Bo Yu, Jennifer King, Adams Zhang, Satyn Kaura, Zhai Qing. A cost utility analysis from a Chinese health care perspective of Nab-paclitaxel or docetaxel, both as alternatives to solvent-based paclitaxel in metastatic breast cancer (MBC) [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 P1-10-05.

Cost-Effectiveness of Taxanes in the Treatment of Metastatic Breast Cancer: A Review of the Literature

Background/Aims: Metastatic breast cancer (MBC) is an incurable disease in which regardless of treatment, total survival time is often less than a year. In these patients suffering from MBC, mitigation of symptoms, reducing side effects of therapy and enhancing quality of life are the major issues in selecting a treatment. Taxanes have been shown to be efficacious as single agents or in combination with other agents as compared to other chemotherapy regimens. Docetaxel has received more support over paclitaxel in many analyses that have compared the two drugs indirectly. A direct comparison of both docetaxel and paclitaxel has not been possible until recently due to a lack of randomized trials. Little is known in reference to cost-effectiveness of taxanes in the treatment of MBC when compared directly. The objective of this literature review was to assess cost-effectiveness literature comparing docetaxel and paclitaxel in MBC.

PCN161 - Nab-Paclitaxel or Docetaxel as Alternatives to Solvent-Based Paclitaxel in Metastatic Breast Cancer (Mbc): A Cost Utility Analysis from a Chinese Health Care Perspective

PCN161 - Nab-Paclitaxel or Docetaxel as Alternatives to Solvent-Based Paclitaxel in Metastatic Breast Cancer (Mbc): A Cost Utility Analysis from a Chinese Health Care Perspective

A phase I trial of palbociclib and paclitaxel in metastatic breast cancer.

527 Background: Palbociclib (Palb) is an oral CDK 4/6 inhibitor that is under development in breast cancer as a single agent and in combination with endocrine therapy. Preclinical studies suggest t...

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer.

BackgroundNab-paclitaxel is a novel nanoparticle, albumin-bound, solvent-free, taxane-based chemotherapy approved for the treatment of metastatic breast cancer (MBC). This study reports clinical benefit and toxicities experienced by women with MBC treated with nab-paclitaxel.MethodsWomen with MBC treated with single-agent nab-paclitaxel between January 2012 and March 2014 were included in this analysis. Retrospective data obtained included demographics, disease characteristics, prior chemotherapy, nab-paclitaxel treatment, toxicity and survival. Clinical benefit was defined as partial or complete response or stable disease (by clinical or radiologic evaluation, or both) at 6 months or more.ResultsOverall response rates (complete or partial responses) were 43% (95% CI: 35.3 - 60.0) for all patients. Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 3 sensory neuropathy (14.3%), grade 4 neutropenia (7.14%) and grade 4 febrile neutropenia (7.14%). Patients received a median of six treatment cycles; three patients had 25% dose reductions because of toxicities.ConclusionsOur clinical experience demonstrates that most women treated with nab-paclitaxel experienced some clinical benefit. Patients achieving clinical benefit lived significantly longer than those who did not. Nab-paclitaxel was well tolerated, with the primary toxicity being mild sensory neuropathy. Nab-paclitaxel represents another treatment option, with a favorable toxicity profile, for women with MBC.

Abstract OT2-6-03: A single arm, preoperative, pilot study to evaluate the safety and biological effects of orally administered reparixin in early breast cancer patients who are candidates for surgery

Abstract Background: Breast cancer stem cells (BCSCs) have the ability to self renew and generate the full range of cells that make up a bulk tumor. Chemokine receptor 1 (CXCR1) is almost exclusively expressed in the aldehyde dehydrogenase-1 positive (ALDH-1+) BCSC population compared with its expression in bulk tumor cells. CXCR1 is a receptor for CXCL8 (previously IL8), a proinflammatory chemokine implicated in the metastasis and progression of multiple malignancies, including breast cancers. CXCL8 has also been shown to stimulate self-renewal of BCSCs in vitro. Reparixin, a low molecular weight blocker of CXCL8 biological activity, reduced ALDH-1+ cells in a human breast cancer xenograft when administered alone or in combination with taxane chemotherapy, and reduced metastases. Based on these findings, a phase 1b study of reparixin in combination with paclitaxel in metastatic breast cancer was initiated and is completing enrolment. This small, pilot, window of opportunity study aims at exploring the safety and effects of reparixin on BCSC markers in early breast cancer. Design and Treatment: Reparixin oral tablets 1000 mg will be given 3 times daily (tid) for 21 consecutive days in the interval prior to planned surgery. Main Eligibility Criteria: Patients must be female aged &amp;gt; 18 years with ER-/PR-/HER-2 negative or ER+/PR+/HER-2 negative stage II and IIa operable breast cancer, with clinical tumor diameter of at least 2 cm, have had no prior surgery, radiotherapy, hormone therapy or chemotherapy, must be willing to undergo two mandatory tumor biopsies (pre- and post-therapy) that are not required for standard care. Objectives: Primary: 1) Evaluate the effects of orally administered reparixin on BCSCs in the primary tumor and the tumoral microenvironment by measuring: a) effects on BCSCs, in tissue samples by flow cytometry or RT-PCR and immunohistochemistry (IHC) b) pathway markers, Phosphatase and tensin homolog (PTEN) and CXCR1 levels in tissue samples by IHC c) Markers of inflammation in plasma samples and leukocyte subsets and study polymorphonuclear nuclear leukocyte [PMN] biology in peripheral blood samples d) Markers of angiogenesis, tumor infiltrating leukocytes, autophagy and EpCAM and EMT markers in tumor tissue samples 2) Evaluate the safety of oral reparixin administered three times daily (tid) for 21 consecutive days. Secondary: To define the pharmacokinetic (PK) profile of single agent orally administered reparixin. Statistical Methods: Comparative Analysis of pre- versus post-treatment biomarker results will be performed. In addition, exploratory correlative analyses may be carried out comparing changes in biomarker expression between selected biomarkers. Additional correlative analyses between biomarker results at specific timepoints may be investigated similarly. Safety and tolerability analysis will be applied on the safety population with descriptive statistics for the safety variables. Summary statistics will be performed for each PK parameter and correlative study parameter. Accrual status: To date, three subjects have been enrolled. Target accrual is 40 subjects. Contact for further Information: pieradelchi.ruffini@dompe.it. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-03.

Anhydramnios following trastuzumab and paclitaxel for metastatic breast cancer in pregnancy

Anhydramnios following trastuzumab and paclitaxel for metastatic breast cancer in pregnancy