Cancer Res Treat.  2019 Jan;51(1):43-52. 10.4143/crt.2017.562.

Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01)

• Park IH
• Im SA
• Jung KH
• Sohn JH
• Park YH
• Lee KS
• Sim SH
• Park KH
• Kim JH
• Nam BH
• Kim HJ
• Kim TY
• Lee KH
• Kim SB
• Ahn JH
• Lee S
• Ro J

• KMID: 2437597
• DOI: http://doi.org/10.4143/crt.2017.562

Abstract

PURPOSE
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
MATERIALS AND METHODS
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
RESULTS
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
CONCLUSION
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

Keyword

Metastatic breast cancer; Irinotecan; Capecitabine; Clinical trial; Progression free survival

MeSH Terms

Arm
Breast Neoplasms*
Breast*
Capecitabine*
Diarrhea
Disease-Free Survival
Epidermal Growth Factor
Global Health
Hand-Foot Syndrome
Humans
Neutropenia
Quality of Life
Triple Negative Breast Neoplasms
Weights and Measures
Capecitabine
Epidermal Growth Factor

Figure

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  Fig. 1. Study flowchart. ITT, intention-to-treat.

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  Fig. 2. Survival analysis in the intention-to-treat population. Kaplan-Meier curve for progression-free survival (PFS) (A) and overall survival (OS) (B) between irinotecan and capecitabine combination (IX) and capecitabine alone (X). mPFS, median PFS; mOS, median OS; CI, confidence interval.

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  Fig. 3. The forest plots of progression-free survival in subgroups stratified by clinical factors. IX, irinotecan and capecitabine combination; X, capecitabine; HR, hazard ratio; CI, confidence interval; TNBC, triple negative breast cancer.

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  Fig. 4. Survival analysis in the triple negative breast cancer subgroup. Kaplan-Meier curve for progression-free survival (PFS) (A) and overall survival (OS) (B) between irinotecan and capecitabine combination (IX) and capecitabine alone (X). mPFS, median PFS; mOS, median OS; CI, confidence interval.

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  Fig. 5. Quality of life measurement. (A) The difference between baseline and each time point in global health and functional subscales. Positive values meant improved state compared with baseline. (B) The change in symptom subscales from baseline. In contrast to functional subscales, negative values meant improved state. IX, irinotecan and capecitabine combination; X, capecitabine. *p > 0.05.

Reference

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