Capecitabine (Page 8 of 11)

14.2 Metastatic Breast Cancer

In Combination With Docetaxel:

The efficacy of capecitabine in combination with docetaxel was evaluated in an open-label, multicenter, randomized trial (Study SO14999). Eligible patients had metastatic breast cancer resistant to, or recurring during or after an anthracycline-containing therapy, or relapsing during or recurring within 2 years of completing an anthracycline-containing adjuvant therapy were enrolled. Patients were randomized to capecitabine 1,250 mg/m 2 twice daily for the first 14 days of a 21-day cycle and docetaxel 75 mg/m 2 as a 1-hour intravenous infusion on day 1 of day of a 21-day cycle or docetaxel 100 mg/m 2 as a 1-hour intravenous infusion on day 1 of a 21-day cycle. The efficacy outcome measures were time to disease progression, overall survival, and response rate.

Patient demographics are provided in Table 14.

Table 14: Baseline Demographics in Metastatic Breast Cancer (Study SO14999)

Capecitabine + Docetaxel (N=255)

Docetaxel (N=256)

Age (median, years)

  1. 52
  1. 51

Karnofsky Performance Status (median)

  1. 90
  1. 90

Site of Disease

  1. Lymph nodes, %
  1. 47
  1. 49
  1. Liver, %
  1. 45
  1. 48
  1. Bone, %
  1. 42
  1. 46
  1. Lung, %
  1. 37
  1. 39
  1. Skin, %
  1. 29
  1. 29

Prior Chemotherapy

  1. Anthracycline 1 , %
  1. 100
  1. 100
  1. Fluorouracil, %
  1. 77
  1. 74
  1. Paclitaxel, %
  1. 10
  1. 9

Resistance to an Anthracycline

  1. No resistance, %
  1. 7
  1. 7
  1. Progression on anthracycline therapy, %
  1. 26
  1. 29
  1. Stable disease after 4 cycles of anthracycline therapy, %
  1. 16
  1. 16
  1. Relapsed within 2 years of completion of anthracycline-adjuvant therapy, %
  1. 31
  1. 29
  1. Experienced a brief response to anthracycline therapy, with subsequent progression while on therapy or within 12 months after last dose, %
  • 20
  • 20

No. of Prior Chemotherapy Regimens for Treatment of Metastatic Disease

  1. 0, %
  1. 35
  1. 31
  1. 1, %
  1. 48
  1. 53
  1. 2, %
  1. 17
  1. 15
  1. 3, %
  1. 0
  1. 1

1. Includes 10 patients in combination and 18 patients in single agent arms treated with an anthracenedione

Efficacy results are shown in Table 15, Figure 4 and Figure 5.

Table 15: Efficacy Results in Metastatic Breast Cancer (Study SO14999)

  1. Efficacy Parameter

Capecitabine + Docetaxel (N=255)

Docetaxel (N=256)

  1. Time to Disease Progression
  1. Median, months
  1. 6.1
  1. 4.2
  1. 95% CI
  1. (5.4, 6.5)
  1. (3.5, 4.5)
  1. Hazard Ratio
  1. 0.643
  1. p-value
  1. 0.0001
  1. Overall Survival
  1. Median, months
  1. 14.5
  1. 11.6
  1. 95% CI
  1. (12.3, 16.3)
  1. (9.8, 12.7)
  1. Hazard Ratio
  1. 0.775
  1. p-value
  1. 0.0126
  1. Response Rate 1
  1. 32%
  1. 22%

1. The response rate reported represents a reconciliation of the investigator and IRC assessments performed by the sponsor according to a predefined algorithm.

Figure 4 Kaplan-Meier Estimates for Time to Disease Progression in Metastatic Breast Cancer (Study SO14999)

Figure 4
(click image for full-size original)

Figure 5 Kaplan-Meier Estimates of Survival in Metastatic Breast Cancer (Study SO14999)

Figure 5
(click image for full-size original)

Single Agent:

The efficacy of capecitabine as a single agent was evaluated in an open-label single-arm trial (Study SO14697). Eligible patients had metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated (e.g., patients who have received cumulative doses of 400 mg/m 2 of doxorubicin or doxorubicin equivalents). Resistance was defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant chemotherapy regimen. Patients received capecitabine 1,255 mg/m 2 orally twice daily for first 14-days of a 21-day treatment cycle. The major efficacy outcome measure was tumor response rate in patients with measurable disease, with response defined as a ≥50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease for at least 1 month.

The baseline demographics are shown in Table 16.

Table 16: Baseline Demographics in Metastatic Breast Cancer (Study SO14697)

  • Patients With Measurable Disease (N=135)
  • All Patients (N=162)

Age (median, years)

  1. 55

56

Karnofsky Performance Status

  1. 90

90

No. Disease Sites

  1. 1-2, %
  1. 32

37

  • 3-4, %
  • 46

43

  • >5, %
  • 22

21

Dominant Site of Disease

  1. Visceral 1 , %
  1. 75

68

  • Soft Tissue, %
  • 22

22

  • Bone, %
  1. 3

10

Prior Chemotherapy

  1. Paclitaxel, %
  1. 100

100

  • Anthracycline 2 , %
  • 90

91

  • Fluorouracil, %
  • 81

82

  • Resistance to Paclitaxel, %
  • 76

77

  • Resistance to an Anthracycline 2 , %
  • 41

41

  • Resistance to both Paclitaxel and an Anthracycline 2 , %
  • 32

31

1. Lung, pleura, liver, peritoneum

2. Includes 2 patients treated with an anthracenedione

Efficacy for Study SO14697 are shown in Table 17.

Table 17: Efficacy Results in Metastatic Breast Cancer (Study SO14697)

Efficacy Parameter

  1. Resistance to Both Paclitaxel and an Anthracycline
  2. (N=43)

Response Rate 1

(95% CI)

  1. 25.6%
  2. (13.5, 41.2)

Complete Response

  1. 0%

Partial Response 1

  1. 11%

Duration of Response 1

Median, months 2 (Range)

  • 5.1 (2.1-7.7)

1. Includes 2 patients treated with an anthracenedione

2. From date of first response

For the subgroup of 43 patients who were doubly resistant, the median time to progression was 3.4 months and the median survival was 8.4 months. The objective response rate in this population was supported by a response rate of 18.5% (1 CR, 24 PRs) in the overall population of 135 patients with measurable disease, who were less resistant to chemotherapy (see Table 15). The median time to progression was 3.0 months and the median survival was 10.1 months.

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