Abstract P1-19-44: Real-world efficacy and safety of palbociclib combined with fulvestrant in japanese patients with ER-positive HER2-negative advanced or metastatic breast cancer
Authors: Hirohito Seki, Takashi Sakurai, Yuka Maeda, Naohiko Oki, Mina Aoyama, Ryou Yamaguchi, Ken Shimizu, Kaori Higeta
Journal: Cancer Research (2020)

Abstract Background: Targeting the molecular components of the cell cycle to interfere with cell cycle progression is a logical strategy for cancer treatment. Cyclin-dependent kinase (CDK) 4 and 6 promote cell cycle progression. Palbociclib is a selective inhibitor of CDK4 and CDK6 that obstructs progression from the G1 phase to the S phase and inhibits subsequent DNA synthesis. Palbociclib has been approved as a novel molecular targeting drug for hormone receptor-positive/HER2- advanced or metastatic breast cancer (MBC) combined with endocrine therapy. In a phase 3 trial, palbociclib-fulvestrant (PF) significantly improved progression-free survival (PFS) of patients with ER+/HER2- advanced or MBC. However, in Japanese patients, did not improve in the PF group. Moreover, neutropenia was higher in Japanese patients. We conducted a retrospective study to verify the efficacy and safety of PF in Japanese patients. Methods: Thirty-nine ER+/HER2- advanced or MBC patients treated with fulvestrant (F) alone and 31 patients treated with PF at the Saitama Medical Center from July 2012 to November 2018 were included. Fulvestrant 500 mg was administered intramuscularly on days 1 and 15 of cycle 1, and then every 28 days thereafter starting from day 1 of cycle 1. Palbociclib 125 mg/day was administered orally on days 1 to 21, followed by 7 days off treatment for every 28-day cycle. Premenopausal and perimenopausal women were also treated with LHRH agonist subcutaneously. Results: In the F and PF groups, the complete response were 0% and 3.2%, respectively, the partial response were 2.6% and 38.7%, respectively, and the rates of long stable disease were 20.5% and 22.6%, respectively. Therefore, the objective response rate in the F and PF groups were 2.6% and 41.9% (P &amp;lt; 0.001), respectively, and the clinical benefit rate (CBR) were 23.1% and 61.3% (P = 0.002), respectively. We observed significant differences in the CBR in patients with the following characteristics: age &amp;lt;70 years (F: 16.7% vs PF: 63.2%; P = 0.002), BMI ≥25 (F: 10% vs PF: 69.2%; P = 0.001), ≤1 previous endocrine therapy (F: 21.1% vs PF: 60%; P = 0.001), ≤1 previous chemotherapy (F: 21.1% vs PF: 61.5%; P = 0.002), no sensitivity to prior endocrine therapy (F: 22.5% vs PF: 60%; P = 0.0049), stage I-III at initial diagnosis (F: 23.3% vs PF: 59.1%; P = 0.011), DFI ≥24 months (F: 30% vs PF: 69.2%; P = 0.038), two or more metastatic sites (F: 21.7% vs PF: 65%; P = 0.006), and visceral metastasis (F: 22.7% vs PF: 73.3%; P = 0.006). The median PFS was significantly improved in the PF (PF vs F: 13.3 months vs 3.9 months, HR, 0.272, 95% CI, 0.128-0.574, p &amp;lt; 0.001). The most common adverse events reported for the PF group were leukopenia, neutropenia, anemia, and fatigue. Hematologic adverse events were more frequent in the PF group than in the F group. There was also no febrile neutropenia in either group. The most common nonhematologic adverse events were fatigue (41.9% in PF vs 5.2% in F). Fever without neutropenia occurred in two patients in the PF group. The only higher than Grade 3 nonhematologic adverse event was liver dysfunction (5.1%), which occurred in the F group. There were no serious adverse events, such as embolism, in either group. There was no dose discontinuation of palbociclib due to adverse events; however, 58.1% (18/31) of patients required dose interruption and 71% (18/31) required dose reduction due to Grade 3 or 4 neutropenia. Sixteen of 31 (51.6%) patients required one dose-level reduction and 6 of 31 (19.4%) required two dose-level reductions. The median number of courses for the first dose reduction was 2 (range: 1-5), and the median for the second dose reduction was 3 (range: 2-5). Conclusion: PF was tolerable and significantly improved clinical outcome in Japanese patients with ER+/HER2- MBC. Citation Format: Hirohito Seki, Takashi Sakurai, Yuka Maeda, Naohiko Oki, Mina Aoyama, Ryou Yamaguchi, Ken Shimizu, Kaori Higeta. Real-world efficacy and safety of palbociclib combined with fulvestrant in japanese patients with ER-positive HER2-negative advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-44.