Pooled analysis of individual patient data from capecitabine monotherapy clinical trials in locally advanced or metastatic breast cancer

• Published in: Breast cancer research and treatment Vol. 136; no. 3; pp. 777 - 788
• Main Authors: Blum, Joanne L., Barrios, Carlos H., Feldman, Nancy, Verma, Sunil, McKenna, Edward F., Lee, Luen F., Scotto, Nana, Gralow, Julie
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2012; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antimitotic agents; Antineoplastic agents; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms, Male - drug therapy; Breast Neoplasms, Male - mortality; Breast Neoplasms, Male - pathology; Cancer research; Cancer therapies; Capecitabine; Clinical Trial; Clinical trials; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Drug therapy; Female; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Gynecology. Andrology. Obstetrics; Hand-Foot Syndrome - etiology; Hormones, Sex; Humans; Male; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Multivariate Analysis; Oncology; Proportional Hazards Models; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Treatment Outcome; Tumors; Young Adult; Metastatic breast cancer; Hormone receptor–positive; Capecitabine; Pretreated; Treatment line; Antineoplastic agent; Breast disease; Metastasis; Hormone receptor―positive; Clinical trial; Advanced stage; Pyrimidine nucleoside; Human; Fluoropyrimidine derivatives; Patient; Breast cancer; Data; Malignant tumor; Prodrug; Mammary gland diseases; Treatment; Analysis; Individual; Locally advanced stage; Monotherapy; Cancer; Hormonal receptor
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-012-2288-x

We assessed the efficacy and safety of capecitabine across treatment lines, and the impact of patient and disease characteristics on outcomes using data from phase II/III trials. Individual patient data were pooled from seven Roche/Genentech-led trials conducted from 1996 to 2008 where single-agent capecitabine was the test or control regimen for metastatic breast cancer (MBC). Data were analyzed from 805 patients: 268 in the first-line metastatic setting and 537 in the second-line or later setting. Baseline characteristics were balanced across treatment lines. Patients receiving second-line or later versus first-line capecitabine had lower objective response rates (ORR: 19.0 vs. 25.0 %, respectively, odds ratio 0.70; 95 % CI: 0.5–1.0) and significantly shorter progression-free survival (PFS: median 112.0 days [3.7 months] vs. 150.0 days [4.9 months]; p  < 0.0001) and overall survival (OS: median 396.0 days [13.0 months] vs. 666.0 days [21.9 months]; p  < 0.0001). In multivariate analysis by backward elimination, significantly improved ORR ( p  = 0.0036), PFS ( p  < 0.0001) and OS ( p  < 0.0001) with capecitabine were demonstrated in patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive versus both ER and PgR-negative tumors. Hand-foot syndrome (HFS) was the most common adverse event (AE) in 63 % of patients. Overall, 7 % of patients discontinued and two patients (<1 %) died from treatment-related AEs. Significantly improved survival was observed in patients developing capecitabine-related HFS ( p  < 0.0001 PFS/OS) or diarrhea ( p  = 0.004 OS; p  = 0.0045 PFS) versus patients without these events. In this pooled analysis of individual patient data, first-line capecitabine was associated with improved ORR, PFS, and OS versus second or later lines. Multivariate analyses identified greater ORR, PFS, and OS with capecitabine in patients with ER and/or PgR-positive versus ER/PgR-negative tumors. Safety was in-line with previous phase III trials in MBC.