Abstract PS13-47: Real world study on the efficacy and tolerability of ixabepilone monotherapy vs. combination therapy with capecitabine in metastatic breast cancer patients (MBC)
Authors: Hyder Tara , Rosenzweig Margaret , Brufsky Adam M 
Published: February 2021

BACKGROUND: Ixabepilone is a microtubule stabilizing agent that was approved as monotherapy and in combination with capecitabine for the treatment of refractory metastatic or locally advanced breast cancer resistant to anthracyclines, taxanes. With limited options for refractory MBC, especially in triple negative breast cancer (TNBC), ixabepilone plus capecitabine has demonstrated an increase in progression free survival (PFS) compared to patients treated with capecitabine alone. We assess the effectiveness and safety of the drug in a real-world setting. METHOD: REDCAPS is a large, ongoing clinical database of over 1800 women (1999 to present) was used to identify 91 patients who had received ixabepilone monotherapy and in combination with capecitabine during their treatment course at the Magee Women’s Hospital, Women’s Cancer Center. Clinical outcomes were retrospectively analyzed utilizing descriptive and comparative statistics. RESULTS: Patients were heavily pretreated: 41.8% had received at least 6 lines of prior chemotherapy in the metastatic setting. Treatment was late in the disease course; median line of treatment was 5.3. At the time of receiving ixabepilone, the patients had multiple metastases (64.8% have &gt; 3) and widespread disease (57% had both visceral and non-visceral disease). PFS was 3.5 months with n=4 patients attaining a PFS &gt; 12 months. Overall survival (OS) was 11.3 months. A subset of patients that had triple negative breast cancer (N=37) had similar PFS, 3.6 months, and OS, 10.2 months, as the total population of patients that received the medication. Another subset analysis was conducted looking at patients who had received ixabepilone monotherapy (82 patients) vs those who had received combination therapy with ixabepilone and capecitabine (9 patients). The PFS and OS was not statistically significant between the two groups. Most common adverse events of any grade were fatigue (37%), nausea (32%), and peripheral sensory neuropathy (28%). Grade 3 or higher anemia was present in 10% of the patients. CONCLUSION: Ixabepilone monotherapy and in combination with capecitabine has demonstrated efficacy in the treatment of heavily pretreated patients with MBC, including the challenging population of TNBC patients in this real-world example. While the number of patients receiving the combination therapy was low (n=9), PFS and OS were still demonstrated to be comparable to monotherapy. It is also well tolerated. These findings make ixabepilone a reasonable chemotherapeutic agent for refractory MBC and TNBC patients with visceral metastases, more than 3 metastatic disease sites, poor prognosis and who have limited treatment options after having failed anthracycline or taxane treatment.

Ixabepilone Treatment in TNBC PatientsAll patients (N=91)TNBC (N=37)Age, yearsMedian (Range)&lt;50&gt;=5048.1 (32.6-85.1)56 (61.5)35 (38.5)49.4 (28.8-85.1)20 (54.1)17 (45.9)Number of metastatic sites&lt; 3&gt; 332 (35.2)59 (64.8)14 (37.8)23 (62.2)Type of metastatic disease sitesVisceralNot visceralCombined21 (23.1)13 (14.3)57 (62.6)11 (29.7)7 (18.9)19 (51.4)Anthracycline or taxane received prior to ixabepilone in neoadjuvant/adjuvant settingYes No71 (78.0)20 (22.0)32 (78.0)5 (5.0)Anthracycline or taxane received prior to ixabepilone in metastatic settingYesNo67 (23.1)24 (76.9)26 (70.3)11 (29.7)Number of prior regimens prior to ixabepilone in metastatic setting Median 12345=&gt; 65.3 5 (5.5)2 (2.2)14 (15.4)15 (16.5)17 (18.7)38 (41.8)4.2 4 (10.8)1 (2.7)9 (24.3)9 (24.3) 6 (16.2)8 (21.6)Progression free survival, monthsMedian (Range)95% CI3.53 (0.33-22.73)2.68-4.383.56 (0.33-22.73)1.92-5.20Overall survival, monthsMedian (Range)95% CI11.34 (0.33-67.73)8.52-14.2610.10 (0.33-54.03)6.09-14.13

Treatment with Ixabepilone Monotherapy vs. Combined with CapecitabineAll PatientsIxabepilone monotherapy (n=82)Ixabepilone+capecitabine(n=9)Progression free survival (PFS), months Median 95% confidence interval3.58(2.63-4.52)3.11(0.83-5.41)P=0.74Overall Survival (OS), months Median 95% confidence interval11.21(8.18-14.23)13.11(0.64-25.59)P=0.70PFS by line of previous therapy, months &lt;4 (n=21) &gt;=4 (n=70)2.403.813.013.28P=0.64P=0.84OS by line of previous therapy, months &lt;4 (n=21) &gt;=4 (n= 70)9.8411.5115.737.88P=0.41P=0.67

Citation Format: Tara Hyder, Margaret Rosenzweig, Adam M Brufsky. Real world study on the efficacy and tolerability of ixabepilone monotherapy vs. combination therapy with capecitabine in metastatic breast cancer patients (MBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-47.