Masaoki Sasaki

Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients.

This phase I study in Japanese patients evaluated the safety, pharmacokinetics, and preliminary efficacy of palbociclib, a highly selective and reversible oral cyclin‐dependent kinase 4/6 inhibitor, as monotherapy for solid tumors (part 1) and combined with letrozole as first‐line treatment of postmenopausal patients with estrogen receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer (part 2). Part 1 evaluated palbociclib 100 and 125 mg once daily (3 weeks on/1 week off; n = 6 each group) to determine the maximum tolerated dose. Part 2 evaluated palbociclib maximum tolerated dose (125 mg) plus letrozole 2.5 mg (n = 6). The most common treatment‐related adverse event was neutropenia (all grades/grade 3/4): 100 mg, 83%/67%; 125 mg, 67%/33%; and palbociclib plus letrozole, 100%/83%. Heavier pretreatment with chemotherapy may have resulted in higher neutropenia rates observed with the 100‐mg dose. Palbociclib exposure was higher with 125 vs 100 mg (mean area under the plasma concentration–time curve over dosing interval [τ]: 1322 vs 547.5 ng·h/mL [single dose], 2838 vs 1276 ng·h/mL [multiple dose]; mean maximum plasma concentration: 104.1 vs 41.4 ng/mL [single dose], 185.5 vs 77.4 ng/mL [multiple dose]). Half‐life was 23–26 h. No drug–drug interactions between palbociclib and letrozole occurred. Four patients had stable disease (≥24 weeks in one patient with rectal cancer [100 mg] and one with esophageal cancer [125 mg]) in part 1; two patients had partial response and two had stable disease (both ≥24 weeks) in part 2. Palbociclib at the 125‐mg dose (schedule 3/1) was tolerated and is the recommended dose for monotherapy and letrozole combination therapy in Japanese patients. The trials are registered with www.ClinicalTrials.gov: A5481010 and NCT01684215.

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

OBJECTIVE For patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain. PATIENTS AND METHODS This multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla. RESULTS Median follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56). CONCLUSION Our study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.

Quality evaluation of medical care for breast cancer in Japan

OBJECTIVE The purpose of this study is to measure adherence rate to the quality indicators (QI) in clinical practice to evaluate the quality of care for breast cancer patients in Japan. DESIGN A retrospective record review. SETTING Two hundred twenty-four designated breast cancer care hospitals throughout Japan. PARTICIPANTS A total of 15 227 patients diagnosed with breast cancer in 2005. MAIN OUTCOME MEASURES The adherence rate of seven items that correspond to QIs of medical care, which were developed using an adaptation of RAND/UCLA (University of California, Los Angeles) appropriateness method. RESULTS The lowest quality score was the drug therapy adherence to the St. Gallen consensus recommendations, for which the overall quality score 52.8%. The highest quality score was the adherence rate of hormone receptor testing, for which overall quality score was 97.8%. The greatest variations across facilities were for HER-2 testing and for radiation therapy after breast-conserving surgery. The least variation was for hormone receptor testing. CONCLUSIONS There was a range of measurements for the adherence rate to each QI, suggesting that the desired standards of care had not necessarily pervaded all facilities. It is necessary to strive for widespread implementation of QIs and realization of the significance of measuring the medical care quality among physicians treating breast cancer.

Follicular dendritic cell sarcoma treated with a variety of chemotherapy

Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor derived from follicular dendritic cells. Radical resection is the standard therapy for patients with local disease, but an optimal chemotherapy regimen has not been determined for unresectable disease. We report our experience of an FDCS patient with multiorgan involvement. In the present case, disease was only located in the pancreas initially and radical resection was performed. Multiple metastasis developed after the treatment and several factors that indicated a poor prognosis were observed. The present case had a very poor prognostic disease but survived for a long time with a good performance status because of the multiple chemotherapy regimens, which follow therapeutic strategies for malignant lymphoma and soft tissue sarcoma. As far as we know, this is the first study reporting the indication of bendamustine for FDCS patients.

326PTRANSITION OF RECURRENCE-FREE SURVIVAL FOR EARLY-STAGE BREAST CANCER AT NATIONAL CANCER CENTER HOSPITAL EAST

ABSTRACT Aim: The prognosis for breast cancer has recently been improved by the development of numerous, active chemotherapeutic regimens and hormone therapies. Some reports from the United States and Europe have described improved prognoses for recurrent breast cancer. This study investigated how recurrence-free survival (RFS) after complete resection has improved over time for women with early-stage breast cancer treated at our institute. Methods: We retrospectively analyzed RFS in 2,958 female patients with primary breast cancer who underwent complete resection between July 1992 and December 2010 at National Cancer Center Hospital East in Japan. Medical records were reviewed to obtain patient background, treatment for the initial disease, and RFS as estimated using the Kaplan-Meier product-limit method. The primary outcome was to evaluate the association between the year of treatment and subsequent RFS. Results: Patients were divided into the following four groups according to the year of surgery: 1992-1997; 1998-2001; 2002-2006; and 2007-2010. A significant improvement was seen in RFS across the four groups, with more recent groups showing longer RFS (P Conclusions: For these groups of patients, our study shows that RFS for early-stage breast cancer after complete resection improved between 1992 and 2010. Disclosure: All authors have declared no conflicts of interest.

461PSAFETY, PHARMACOKINETICS (PK) AND EFFICACY OF CYCLIN-DEPENDENT KINASE (CDK) 4 AND 6 INHIBITOR, PALBOCICLIB (PD-0332991): RESULTS FROM A PHASE 1 STUDY IN JAPANESE PATIENTS (PTS)

ABSTRACT Aim: Palbociclib is a potent and highly selective reversible oral inhibitor of CDK 4/6. This ongoing phase 1 study evaluates the safety, PK and preliminary efficacy of palbociclib as a single agent in Japanese pts with solid tumors (part 1) and in combination with letrozole (LET) in 1st-line treatment of Japanese postmenopausal pts with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer (part 2). Methods: Two dose levels (100 and 125 mg; n = 6 each) of palbociclib monotherapy once daily were studied in a 3-wk-on/1-wk-off treatment schedule (schedule 3/1) to evaluate the maximum tolerated dose (MTD) in part 1. The MTD of palbociclib (decided in part 1) was then used in combination with LET 2.5 mg in part 2 (n = 6). Results: Dose-limiting toxicity was noted in 1 pt at each dose level: 24 wks in 1 esophageal cancer pt at 125 mg); 2 pts had unconfirmed partial response and 2 had SD in part 2. Conclusions: Hematologic toxicities were common with palbociclib monotherapy and combination therapy. Although a higher than dose-proportional increase in exposure was observed at 125 mg, the 125-mg dose (schedule 3/1) was tolerated and considered a recommended dose for monotherapy and LET combination therapy in Japanese pts. Disclosure: H. Mukai, T. Yoshino, S. Osera, M. Sasaki, C. Shimizu, K. Yonemori, M. Koudaira, Y. Tanabe and K. Tamura: corporate(Pfizer)-sponsored research; N. Matsuda, N. Mizutani,Y. Mori, S. Hashigaki,T. Nagasawa and Y. Umeyama: Employee of Pfizer Japan; S. Randolph: Employee of Pfizer Oncology.