Most Read Articles
Dr. Alexander Drilon, 19 Jul 2017
With the dramatic evolution of sequencing technology and emergence of effective targeted therapies, using a comprehensive molecular approach to guide treatment decisions is becoming more accessible and applicable in the clinic. At the recent Foundation Medicine meeting in Hong Kong, Dr Alexander Drilon, clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSKCC), New York, US, discussed the current landscape and potential benefits of comprehensive molecular profiling in non-small cell lung cancer (NSCLC).

Utidelone-capecitabine combo provides longer PFS vs capecitabine alone in resistant breast cancer

Jairia Dela Cruz
18 Apr 2017

Adding utidelone to capecitabine appears to significantly improve the progression-free survival (PFS) in women with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens, according to the results of a phase III trial. Utidelone toxicity is mild, with the exception of peripheral sensory neuropathy.

The multicentre, open-label trial randomized 450 patients (median age 50 years) to 21-day cycles of either utidelone plus capecitabine (30 mg/m2 intravenously once per day on days 1 to 5; 1,000 mg/m2 orally twice per day on days 1 to 14, respectively) or capecitabine alone (1,250 mg/m2 orally twice per day on days 1 to 14). Treatment was given until disease progression or unacceptable toxicity occurred.

Compared with patients who received capecitabine alone, those treated with the utidelone—capecitabine combination had significantly longer PFS, the primary endpoint of the study (median PFS, 8.44 vs 4.27 months; hazard ratio [HR], 0.46; 95 percent CI, 0.36 to 0.59; p<0.0001). The median follow-up was 6.77 months in the combination arm vs 4.55 months in the monotherapy arm. [Lancet Oncol 2017;18:371–383]

Data on 155 deaths, although immature for an analysis of overall survival (which had been prespecified after 310 deaths), showed overall survival to be better with the utidelone—capecitabine combination vs capecitabine alone (16.13 vs 12.78 months; HR, 0.63; 0.45 to 0.88; log-rank p=0.0059).

No significant between-group differences were observed in the occurrence of treatment-emergent adverse events (AEs) including palmar-plantar erythrodysesthesia, haematological toxicities and gastrointestinal toxicities. However, considerably more patients in the combination group developed grade 3 peripheral neuropathy (22 vs <1 percent in the capecitabine alone group).

Serious adverse events were also comparable between the two treatment groups (16 events in the combination group vs 14 events in the monotherapy group), and the most commonly reported was diarrhoea.

“The results of this study strongly support that utidelone is a promising investigational drug. It offers an effective therapeutic option combined with capecitabine with manageable toxicity for patients with metastatic breast cancer who were resistant to several previous courses of chemotherapy including anthracyclines and taxanes,” researchers said.

Breast cancer is the most common cancer in women, according to data from the International Agency for Research on Cancer and World Health Organization, with more than 1.7 million new cases diagnosed worldwide in 2012. Researchers noted that the widespread use of standard chemotherapy, especially anthracyclines and taxanes, in the adjuvant setting of breast-cancer care might have contributed to an increase in a heavily pretreated and drug-resistant metastatic breast cancer population and a risk of cumulative toxicities.

Utidelone is an analogue of epothilones—a drug class that, like taxanes, prevents the division of cancer cells by inhibiting microtubule depolymerisation. Despite this similarity, utidelone and taxanes have different molecular structure and mechanism of action. “Thus, patients with tumours resistant to taxanes remain sensitive to epothilones,” researchers said. [Curr Top Med Chem 2014;14:2312–21; Proc Natl Acad Sci USA 2000;97:2904–09]

Belonging to the same class as utidelone, ixabepilone is the only drug in this class that has been approved by the US Food and Drug Administration in patients with metastatic breast cancer. In previous phase II and III trials, the drug produced an improvement in PFS of about 2 months in patients with taxane-resistant metastatic breast cancer, although it did not provide an overall survival advantage. [J Clin Oncol 2007;25:3399–414; 5210–17; J Clin Oncol 2010;28:3256–63]

Compared with ixabepilone, utidelone provides greater PFS advantage, has a more favourable safety profile and the potential to be produced at a lower cost, researchers said.

They pointed out that unpublished data from previous phase I and preclinical studies indicated that utidelone showed antitumour activity for other human cancers, including lung, liver, colon and prostate cancer, and cancers resistant to taxanes and other chemotherapies.

“Therefore, utidelone could potentially become a novel therapeutic option for other malignancies in the armamentarium of cancer treatment, especially for cancers that are resistant to multiple drugs,” they said.

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Most Read Articles
Dr. Alexander Drilon, 19 Jul 2017
With the dramatic evolution of sequencing technology and emergence of effective targeted therapies, using a comprehensive molecular approach to guide treatment decisions is becoming more accessible and applicable in the clinic. At the recent Foundation Medicine meeting in Hong Kong, Dr Alexander Drilon, clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSKCC), New York, US, discussed the current landscape and potential benefits of comprehensive molecular profiling in non-small cell lung cancer (NSCLC).