nab-Paclitaxel a hot topic at the San Antonio Breast Cancer Symposium

Recently added to the PBS, the novel nanoparticle albumin bound paclitaxel (Abraxane) proved to be a hot topic when researchers met at the 2009 San Antonio Breast Cancer Symposium.

Drugs belonging to the taxane class of medications are among some of the most important drugs used in the management of early and metastatic breast cancer.¹ Prior to May 2009 paclitaxel (Anzatax; Taxol) and docetaxel (Taxotere) were the only two drugs of this class available in Australia.² However a novel form of paclitaxel, Abraxane (nanoparticle albumin-bound (nab-) paclitaxel, has since been added to the Pharmaceutical Benefits Schedule for use in metastatic carcinoma of breast.^3,4

Compared to solvent based formulations, the use of nab-paclitaxel has many benefits including avoiding toxicities associated with solvent based formulations, decreased use of premedications and shorter infusion times,² as well as increased accumulation of paclitaxel in the area of the tumour.⁵ The latter is facilitated by its interaction with the albumin binding protein SPARC (Secreted Protein Acidic and Rich in Cysteine), which is secreted by approximately 50% of breast cancers.⁵ This protein has been shown to promote angiogenesis at physiological concentrations, contributing to a more aggressive tumour phenotype.⁶ Recently the angiogenic domain of SPARC was localised to the C-terminus of the protein. This is a potential therapeutic target and a biomarker for the prediction of response to nab-paclitaxel,⁶ which is being validated in clinical trials in a number of tumour types.

Some interesting studies were presented at the recent San Antonio Breast Cancer Symposium (SABCS) held in Texas on 10–13 December 2009. The symposium featured a range of interests related to the experimental biology, aetiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease.⁷ Also presented were results related to the use of nab-paclitaxel in the neoadjuvant chemotherapy setting and the costs associated with its use compared to the other solvent based taxanes.

nab-paclitaxel has been shown to be one of the most active agents against metastatic breast cancer. Research presented at SABCS demonstrated its use in combination as a neoadjuvant. A pilot neoadjuvant trial (n=28) in HER2 positive patients combined lapatinib, a dual kinase inhibitor of EGFR and HER2, with nab-paclitaxel. Clinical response rate was used as the primary endpoint with 18 patients showing partial clinical response and four a complete clinical response. Three patients had stable disease. The most common side effects were rash, neuropathy, fatigue and myalgias.⁸

The use of nab-paclitaxel also extends to HER2 negative metastatic breast cancers. HER2 negative metastatic breast cancers typically have low response rates and short progression free survival times with first-line chemotherapy agents. Presented at the symposium were promising findings from a phase II study investigating nab-paclitaxel, bevacizumab and gemcitabine as first line therapy for patients with HER2 negative metastatic breast cancer. Of the 29 patients enrolled, 8 achieved complete response, 14 a partial response, 5 had stable disease and only 2 showed progressive disease. The median progression free survival was 8 months. While there was one reported episode of grade 4 neutropenic fever, the most commonly reported side effects were alopecia, fatigue, bone pain, nausea and skin rash/lesion. This study was based on a pilot study, which showed an almost doubled overall response rate and significantly increased progression free survival with nab-paclitaxel compared to solvent based paclitaxel.⁹

Although solvent based paclitaxel and docetaxel have lower drug acquisition costs than nab-paclitaxel, a recent study showed total medical costs between the three were modest. This US study analysed paid medical claims with total medical costs calculated from the date of first taxane administration to the end of data availability. Over a two-year period more than 2,000 women were identified with 1,035 receiving docetaxel, 997 receiving paclitaxel and 213 receiving nab-paclitaxel. Median total medical costs per patient per month differed by less than US$800. nab-paclitaxel costs were reduced by lower utilisation costs and costs associated with colony stimulating factor.¹⁰

The addition of nab-Paclitaxel to the PBS offers an alternative therapy in the treatment of metastatic breast cancer. The novel nab-paclitaxel avoids the toxicities associated with solvent based preparations and avoids the use of premedication and extended infusion times. Recent research presented at the San Antonio Breast Cancer Symposium explored the molecular interactions of nab-paclitaxel identifying the angiogenic domain of the SPARC protein, a potential therapeutic target and biomarker for the prediction of response to nab-paclitaxel. The research presented supported the use of nab-paclitaxel clinically, in particular in the neoadjuvant setting and a cost analysis demonstrated no increase in total medical costs with the use of nab-paclitaxel compared to other standard taxane preparations.

References

Harries M, Ellis P, Harper P. Nanoparticle albumin-bound paclitaxel for metastatic breast cancer. J Clin Oncol. 2005; 23: 7768-71.
Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, et al. Superior efficacy of albumin-bound paclitaxel, ABI-007, compared with polyethylated castor-oil-based paclitaxel in women with metastatic breast cancer: results of a phase III trial. J Clin Oncol. 2005; 23: 7794-803.
Product Information: Abraxane [online]. Abraxis Bioscience Australia Pty Ltd. September 2008 [cited 24 March 2009]. Available from URL: http://www.abraxane.com.au/
Prescribing Information: Abraxane [online]. MIMS Online. September 2008 [cited 24 March 2009]. Available from URL: http://www.mims.com.au/
Abraxane: mechanism of action (online video recording). Virtual Medical Centre. 2009 [cited 24 March 2009]. Available from URL: / videopage.asp?vidid=485&title=Abraxane:-Mechanism-of-Action
Knauer D, Hwang LY, Lowe C, Hwang J, Norng M, Wu R, et al. Albumin-binding and angiogenic domains of SPARC located at its C-terminus. Paper presented at San Antonio Breast Cancer Symposium, Texas. 11 December 2009.
San Antonio Breast Cancer Symposium. Henry B Gonzalez Convention Center, San Antonio, Texas, USA [online]. Available from URL: http://www.sabcs.org/
Kaklamani V, Uthe R, Khan S, Hansen N, Bethke K, Jeruss J, et al. Pilot neoadjuvant trial with combination of lapatinib and nab-paclitaxel in HER2+ breast cancer. Paper presented at San Antonio Breast Cancer Symposium, Texas. 10 December 2009.
Glück S, Lobo C, Lopes G, Castrellon A, Annapoorna F, Higgins C, et al. Final resuls of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first line therapy for patients with HER2-negative metastatic breast cancer (MBC). Paper presented at San Antonio Breast Cancer Symposium, Texas. 10 December 2009.
Force R. A taxane total cost of care analysis: results of private payor claims data in metastatic breast cancer. Paper presented at San Antonio Breast Cancer Symposium, Texas. 10 December 2009.