Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Mar;24(3):274-287.
doi: 10.1007/s10147-018-1353-9. Epub 2018 Dec 4.

Palbociclib in Combination With Letrozole in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer: PALOMA-2 Subgroup Analysis of Japanese Patients

Affiliations
Free PMC article
Clinical Trial

Palbociclib in Combination With Letrozole in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer: PALOMA-2 Subgroup Analysis of Japanese Patients

Hirofumi Mukai et al. Int J Clin Oncol. .
Free PMC article

Abstract

Background: In PALOMA-2, palbociclib-letrozole significantly improved progression-free survival (PFS) vs placebo-letrozole in women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC) in the first-line setting. We evaluated the efficacy, safety, and pharmacokinetics of palbociclib in Japanese women in PALOMA-2.

Methods: In this phase 3 study, 666 postmenopausal women with ER+/HER2- ABC were randomized 2:1 to palbociclib (125 mg/day [3 weeks on/1 week off]) plus letrozole (2.5 mg daily) or placebo plus letrozole. A prespecified, exploratory, subgroup analysis of Japanese patients (n = 46) was conducted to compare results with those of the overall population.

Results: At the February 26, 2016 cutoff, median PFS among the 46 Japanese patients was 22.2 months (95%CI, 13.6‒not estimable) with palbociclib-letrozole vs 13.8 months (5.6‒22.2) with placebo-letrozole (hazard ratio, 0.59 [95%CI, 0.26-1.34]). The most common adverse events (AEs) were hematologic and more frequent among Japanese patients than the overall population (neutropenia: 93.8% [87.5% grade 3/4] vs 79.5% [66.4%]; leukopenia: 62.5% [43.8%] vs 39.0% [24.8%]); no Japanese patients had febrile neutropenia. Palbociclib dose reductions due to toxicity (mainly neutropenia) were more common in Japanese patients (62.5% vs 36.0%); few permanently discontinued due to AEs. Although mean palbociclib trough concentration was higher in Japanese patients vs non-Asians (95.4 vs 61.7 ng/mL), the range of individual values of the Japanese patients was within that of non-Asians.

Conclusions: These results from PALOMA-2 suggest that palbociclib-letrozole merits consideration as a first-line treatment option for postmenopausal Japanese patients with ER+/HER2‒ ABC. ClinicalTrials.gov: NCT01740427.

Keywords: Advanced breast cancer; HER2−; HR+; Japanese; Letrozole; Palbociclib.

Conflict of interest statement

H. Mukai, C. Shimizu, M. Takahashi, R. Nishimura, and S. Ohsumi have no conflicts of interest to report. N. Masuda has received honoraria from Chugai, AstraZeneca, Pfizer, and Takeda and research funding from Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli Lilly, and Daiichi Sankyo. S. Ohtani has received honoraria from Chugai and Eisai. S. Ohno has received honoraria from Chugai, AstraZeneca, Eisai, Taiho, Novartis, Pfizer, Kyowa-Hakko Kirin, and Sanofi; and research funding from Taiho, Chugai, and Daiichi Sankyo. Y. Yamamoto has received honoraria from Pfizer. N. Sato has received honoraria from Chugai, AstraZeneca, Eisai, Pfizer, and Taiho. H. Iwata has received honoraria and research funding from Pfizer and AstraZeneca, and fees for promotional materials from AstraZeneca. M. Toi has received honoraria from Novartis, MSD, Takeda, AstraZeneca, Taiho, Chugai, Pfizer, Eisai, Eli Lilly, Kyowa-Hakko Kirin, and Genomic Health Institute; research funding from Novartis, AstraZeneca, Taiho, Chugai, Pfizer, and Eli Lilly; served as a consultant/independent contractor for Kyowa-Hakko Kirin and on an advisory board for Genomic Health Institute. S. Hashigaki, Y. Muramatsu, and T. Nagasawa are employees of Pfizer; D. Lu, Y. Mori, and Y. Umeyama are employees of and stockholders in Pfizer.

Figures

Fig. 1
Fig. 1
Investigator-assessed PFS in the a overall population and b Japanese patients (ITT population). CI confidence interval, HR hazard ratio, ITT intent-to-treat, LET letrozole, NE not estimable, PAL palbociclib, PBO placebo, PFS progression-free survival. a HR stratified by disease site (visceral vs nonvisceral) at baseline. b Unstratified HR
Fig. 2
Fig. 2
BICR-assessed PFS in the a overall population and b Japanese patients (ITT population). BICR blinded independent central review, CI confidence interval, HR hazard ratio, ITT intent-to-treat, LET letrozole, NE not estimable, NR not reached, PAL palbociclib, PBO placebo, PFS progression-free survival. a HR stratified by disease site (visceral vs nonvisceral) at baseline. b Unstratified HR
Fig. 3
Fig. 3
PFS after approximately 37 months median follow-up (data cutoff: May 31, 2017) by a investigator assessment and b BICR in Japanese patients (ITT population). BICR blinded independent central review, CI confidence interval, HR hazard ratio, ITT intent-to-treat, LET letrozole, NE not estimable, PAL palbociclib, PBO placebo, PFS progression-free survival. aUnstratified HR
Fig. 4
Fig. 4
Duration of PFS in 32 Japanese patients treated with palbociclib–letrozole. OR objective response, LET letrozole, PD progressive disease, PFS progression-free survival
Fig. 5
Fig. 5
Palbociclib Ctrough at steady state in non-Asian, Asian (excluding Japanese), and Japanese patients. Black diamonds represent the subpopulation arithmetic mean values and open circles represent individual patient values. The dashed blue line represents the arithmetic mean value of all data from all patients. The box plot provides median and 25%/75% quartiles with whiskers to the last point within 1.5 times interquartile range. Ctrough trough concentration
Fig. 6
Fig. 6
Palbociclib Ctrough at steady state vs body weight in non-Asian, Asian (excluding Japanese), and Japanese patients. Pearson product-moment correlation coefficient (R) is presented. Within-patient palbociclib Ctrough are shown. Ctrough trough concentration
Fig. 7
Fig. 7
Posttreatment absolute neutrophil counts vs a baseline absolute neutrophil count, b palbociclib Ctrough, c body weight, and d age. Pearson product-moment correlation coefficients (R) are presented. Absolute neutrophil counts were assessed on day 15 of cycle 1. Ctrough trough concentration

Similar articles

See all similar articles

Cited by 2 articles

References

    1. Nakamura K, Okada E, Ukawa S, et al. Characteristics and prognosis of Japanese female breast cancer patients: The BioBank Japan project. J Epidemiol. 2017;27(S3):S58–S64. doi: 10.1016/j.je.2016.12.009. - DOI - PMC - PubMed
    1. American Cancer Society (2017) Breast Cancer Facts & Figures 2017–2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf. Accessed July 17 2018
    1. Aihara T, Toyama T, Takahashi M, et al. The Japanese Breast Cancer Society Clinical practice guideline for systemic treatment of breast cancer, 2015 edition. Breast Cancer. 2016;23(3):329–342. doi: 10.1007/s12282-016-0670-y. - DOI - PubMed
    1. Cardoso F, Costa A, Norton L, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) Ann Oncol. 2014;25(10):1871–1888. doi: 10.1093/annonc/mdu385. - DOI - PMC - PubMed
    1. Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3(11):1427–1438. - PubMed

Publication types

MeSH terms

Associated data

Grant support

Feedback