Randomized phase II study of <i>nab</i>‐paclitaxel as first‐line chemotherapy in patients with HER2‐negative metastatic breast cancer

Tamura, Kenji; Inoue, Kenichi; Masuda, Norikazu; Takao, Shintaro; Kashiwaba, Masahiro; Tokuda, Yutaka; Iwata, Hiroji; Yamamoto, Nobuto; Aogi, Kenjiro; Sendo, Toshiaki; Nakayama, Takahiro; Sato, Nobuaki; Toyama, Tatsuya; Ishida, Toru; Arioka, Hitoshi; Saito, Mitsue; Ohno, Shinji; Yamauchi, Hideko; Yamada, Kimito; Watanabe, Junichiro; Ishiguro, Hiroshi; Fujiwara, Yasuhiro

doi:10.1111/cas.13221

Cited by 25 publications

(39 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no evidence that paclitaxel agents (solvent based or nanoparticle bound) are less effective than docetaxel; on the contrary, nab-paclitaxel demonstrated improved PFS compared with docetaxel in a prospective randomised trial [8]. Nanoparticle albumin-bound (nab)-paclitaxel appears to offer similar efficacy to docetaxel, with less frequent neutropenia but more frequent sensory neuropathy [9,10]. A single-arm study (N ¼ 51) evaluating weekly paclitaxel combined with trastuzumab and pertuzumab as first-or second-line therapy reported median PFS of 25.7 months and median OS of 33 months [11].…”

Section: Introductionmentioning

confidence: 99%

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Bachelot¹,

Ciruelos²,

Schneeweiß³

et al. 2019

Annals of Oncology

View full text Add to dashboard Cite

See Appendix for individual names.Background: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods:In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results:Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nabpaclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%).Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.ClinicalTrials.gov: NCT01572038.

show abstract

Section: Introductionmentioning

confidence: 99%

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Bachelot¹,

Ciruelos²,

Schneeweiß³

et al. 2019

Annals of Oncology

View full text Add to dashboard Cite

show abstract

“…Search results. After screening 1,902 studies chosen from electronic databases and manual searches, we finally included six eligible randomized trials [2][3][4][5][6]10 for this meta-analysis ( Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…The other 3 trials 2,3,10 included both chemotherapy-naive patients and pretreated patients. By reviewing original studies, we found that two trials excluded patients if they received adjuvant chemotherapy with taxanes (sb-paclitaxel or docetaxel) 12 months prior to study enrollment 2,3 , and another trial only included patients who had no history of chemotherapy after confirmation of metastasis 10 . We concluded that these 3 trials would not be any different from the trials with chemotherapy-naive patients.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis

Lee

Park

Kang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69-3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07-3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62-0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54-0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC. Nanoparticle albumin-bound (nab) paclitaxel is solvent free and employs a novel delivery mechanism for paclitaxel to tumors 1. Although nab-paclitaxel was initially developed to minimize the toxic effects of taxane treatment, several early clinical trials demonstrated that nab-paclitaxel was also more effective than the conventional solvent-based (sb) paclitaxel in the treatment of metastatic breast cancer 2-5. However, recent randomized controlled trials (RCTs) have suggested that nab-paclitaxel chemotherapy is not as efficacious as sb-taxanes, such as sb-paclitaxel and docetaxel, and that nab-paclitaxel is often associated with more frequent adverse events 6. For example, Rugo et al. showed that nab-paclitaxel was not superior to sb-paclitaxel (progression-free survival [PFS] 9.3 months vs 11 months, hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.00-1.45, p = 0.054). Results were concordant with overall survival (OS), and time to treatment failure was significantly shorter in the nab-paclitaxel arm vs the sb-paclitaxel arm 6. Hematologic and non-hematologic toxicity, including peripheral neuropathy, was more prevalent in the nab-paclitaxel arm, which also had more frequent and earlier dose reductions 6. After these conflicting results were generated, Liu et al. conducted a first meta-analysis of randomized clinical trials to evaluate the efficacy and toxicity of nab-paclitaxel compared with sb-paclitaxel and docetaxel in the

show abstract

“…A total of eight studies [10][11][12][13][14][15][16][17] which fulfilled our criteria were included in this study. We did not found any difference in efficacy of nab-paclitaxel over paclitaxel (12 months progression free survival-RR FE = 0.86, 95%CI= 0.77-0.97, p= 0.02, I 2 = 25.07%; 24 months progression free survival-RR FE = 0.86, 95% CI= 0.64-1.16, p= 0.34, I 2 = 0%; and 3 years survival-RR FE = 1.20, 95%CI= 0.92-1.56, p= 0.16, I 2 = 37.55%) (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of Nab-paclitaxel in breast cancer: a meta-analysis

Yadav

Kumar

Rai

2019

Preprint

View full text Add to dashboard Cite

Worldwide breast cancer is the leading cause of cancer related death in women. Paclitaxel is an effective drug used for the treatment of breast cancer but it has many side effects. Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) is an FDA approved drug for the treatment of breast cancer. Currently many clinical trials are conducted to deliver nab-paclitaxel into the tumor cells. But the efficacy and safety of this nab-paclitaxel over conventional paclitaxel still remains questionable. So, we performed a meta-analysis to evaluate the efficacy and safety of nab-paclitaxel in breast cancer treatment. Electronic databases were searched for the suitable studies using key terms 'nab-paclitaxel', 'paclitaxel', and 'clinical trial' with the combination of 'breast cancer' up to August 11, 2019. Risk ratio (RR) and odds ratio (OR) with corresponding 95% confidence intervals (CIs) were calculated. All statistical analyses were performed by the Open Meta-Analyst program. A total of eight studies which fulfilled our criteria were included in this study. For efficacy we retrieved data of 12 months progression free survival, 24 months progression free survival, and overall survival (up to 3 years) and for the safety we took data of nausea, anemia, leukopenia, neutropenia, fatigue, diarrhea and pain. We did not found any difference in efficacy of nab-paclitaxel over paclitaxel (12 months progression free survival- RRFE= 0.86, 95%CI= 0.77-0.97, p= 0.02, I2= 25.07%; 24 months progression free survival- RRFE= 0.86, 95% CI= 0.64-1.16, p= 0.34, I2= 0%; and 3 years survival- RRFE= 1.20, 95%CI= 0.92-1.56, p= 0.16, I2= 37.55%). The meta-analysis of studies used nab-paclitaxel showed reduced adverse effect of anemia (ORFE= 1.66, 95% CI= 1.26-2.19; p= <0.001; I2= 0%) and leukopenia (ORFE= 1.37; 95%CI= 1.06-1.75; p= 0.01; I2= 48.63%). However, in case of other adverse effects no significant association was found with nab-paclitaxel (nausea- ORFE=1.15, 95%CI= 0.94-1.41, p= 0.15, I2= 50.12%; neutropenia- ORRE= 0.75, 95%CI= 0.30-1.87, p= 0.54, I2= 94.45%; fatigue- ORRE= 1.11, 95%CI= 0.77-1.62, p= 0.55, I2= 56.02; diarrhea- ORFE= 1.11, 95%CI= 0.77-1.62, p= 0.55; I2= 34.26; pain- ORRE= 1.15, 95%CI= 0.78-1.69, p= 0.45, I2= 52.96%). In conclusion the use of nab-paclitaxel has reduces the side effects of anemia and leukopenia in breast cancer treatment in comparison to paclitaxel but nab-paclitaxel has no effect on the overall survival of the patients.

show abstract

Randomized phase II study of nab‐paclitaxel as first‐line chemotherapy in patients with HER2‐negative metastatic breast cancer

Cited by 25 publications

References 27 publications

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)

Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis

Efficacy and safety of Nab-paclitaxel in breast cancer: a meta-analysis

Contact Info

Product

Resources

About