Limits...
Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

Inoue K, Kuroi K, Shimizu S, Rai Y, Aogi K, Masuda N, Nakayama T, Iwata H, Nishimura Y, Armour A, Sasaki Y - Int. J. Clin. Oncol. (2015)

Bottom Line: The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin.The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9).The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC.

View Article: PubMed Central - PubMed

Affiliation: Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan. ino@cancer-c.pref.saitama.jp.

ABSTRACT

Background: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients.

Methods: In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles.

Results: The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9).

Conclusions: The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

Show MeSH

Related in: MedlinePlus

Kaplan–Meier estimates for overall survival
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4666271&req=5

Fig1: Kaplan–Meier estimates for overall survival

Mentions: As of the end of the study, 6 patients had died. The remaining 6 patients were censored at the last visit. The median OS as primary endpoint was 35.6 months (95 % CI 23.9, not reached; Fig. 1). PFS was analyzed using the results evaluated by the investigators and the median was 13.9 months (95 % CI 7.6, 27.9; Fig. 2).Fig. 1


Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

Inoue K, Kuroi K, Shimizu S, Rai Y, Aogi K, Masuda N, Nakayama T, Iwata H, Nishimura Y, Armour A, Sasaki Y - Int. J. Clin. Oncol. (2015)

Kaplan–Meier estimates for overall survival
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4666271&req=5

Fig1: Kaplan–Meier estimates for overall survival
Mentions: As of the end of the study, 6 patients had died. The remaining 6 patients were censored at the last visit. The median OS as primary endpoint was 35.6 months (95 % CI 23.9, not reached; Fig. 1). PFS was analyzed using the results evaluated by the investigators and the median was 13.9 months (95 % CI 7.6, 27.9; Fig. 2).Fig. 1

Bottom Line: The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin.The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9).The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC.

View Article: PubMed Central - PubMed

Affiliation: Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan. ino@cancer-c.pref.saitama.jp.

ABSTRACT

Background: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients.

Methods: In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles.

Results: The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9).

Conclusions: The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

Show MeSH
Related in: MedlinePlus