Asian women with endocrine-resistant breast cancer benefit from combination therapy

December 18, 2015

Singapore/Lugano - Data collected in Japanese and Korean patients included in the global PALOMA3 trial provides evidence that combining palbociclib with fulvestrant is an effective strategy to overcome endocrine resistance in women with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer. The analysis of efficacy and safety of the combined therapy in an Asian population was presented (1) at the first ESMO Asia 2015 Congress in Singapore, and results are in line with those reported in all patients (both Asian and non-Asian) earlier this year.

Endocrine resistance is a major clinical issue that makes advanced breast cancer more difficult to treat. Hormone therapy is generally well tolerated and an easy-to-administer option for breast cancer, with demonstrated benefits in patients whose tumours express hormone receptors (HR), particularly the HR+/HER2- subgroup. The ideal option for patients is to be on one endocrine therapy after another, as long as the disease responds or remains unchanged. "However, unavoidably, resistance develops in almost all advanced patients a median ten months after the first-line hormonal agent is administered, and a much shorter median time after the second- or third-line hormonal agents, eventually driving patients to switch to the more toxic chemotherapy," one of the study authors, Dr. Jungsil Ro, Center for Breast Cancer at the National Cancer Center, Goyang, Korea, said.

Palbociclib is an orally active selective inhibitor of the CDK 4/6 growth signal that blocks cell proliferation and cellular division. It has high activity in HR+ breast cancer cell lines and is synergistic in combination with different endocrine therapies.

The PALOMA3 trial assessed the safety and efficacy of the combination of palbociclib and fulvestrant in premenopausal and postmenopausal women with HR+/HER2- advanced breast cancer that progressed during prior endocrine therapy. By March 2015, 105 Asian patients in Korea and Japan were randomised, 74 to receive palbociclib plus fulvestrant and 31 to placebo plus fulvestrant. "For postmenopausal women, the study definitely showed positive results ---progression-free survival more than doubled. Patients suffered from more adverse events in the palbociclib arm, specifically haematologic toxicity, which was easily manageable. "For premenopausal women, the outcome looks as promising as in postmenopausal women, although the numbers are quite small for definitive conclusions," Ro said.

The analysis containing Asian patients nicely confirms that combining palbociclib with fulvestrant is a promising therapeutic approach. "Although median progression-free survival in Asian patients was not reached for the drug combination, it is a reasonable therapeutic option in this population," ESMO spokesperson, Dr. Fabrice André, Institut de Cancérologie Gustave Roussy, Villejuif, France, said. "Palbociclib shows clinical activity with modest toxicity. Although the difference in toxicity profile between Asian and non-Asian populations is really interesting, no clear explanation could be made from this study because of the existing differences reported in non-Asian and Asian patients."

To support the superiority of this drug combination over the hormonal agent alone, a longer follow-up for the overall survival result is needed, Ro said. "So far, we do not have predictive biomarkers to select patients for palbociclib in addition to fulvestrant other than the subtype itself, HR+/HER2- breast cancer. We also need to see that other results from the first-line hormone therapy with palbociclib clinical trial verify the efficacy of the drug, but a longer time is needed to have these results."

Commenting on the results, ESMO spokesperson Dr. Evandro de Azambuja, medical director of the Br.E.A.S.T. Data Centre, Jules Bordet Institute in Brussels, Belgium, not involved in the study, said: "Targeting CDK4/6 represents a further promising option to address endocrine resistance. Other mechanisms of resistance to endocrine therapy include the activation of tyrosine kinase signalling, the up-regulation of the PI3 kinase mammalian target of rapamycin (mTOR) signalling and, lastly, the mutation of ESR1."

On the basis of the impressive results from the phase II PALOMA-1 trial, the combination of palbociclib plus letrozole has been approved by U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal women with ER+, HER2- advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
Notes to Editors


Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.


(1) Abstract 53O_PR, Efficacy and safety of palbociclib plus fulvestrant in Asian women with hormone receptor-positive (HR+)/human epidermal growth factor-2 negative (HER2-) metastatic breast cancer (MBC) that progressed on prior endocrine therapy (ET) J. Ro, S.-A. Im, N. Masuda, Y.-H. Im, K. Inoue, Y. Rai, R. Nakamura, J.H. Kim, K. Zhang, C. Giorgetti, P. Schnell, C. Huang Bartlett, H. Iwata, will be presented during Breast Cancer session on Saturday 19th December, h. 16:30 Abstract will be available online on 18th December 2015, 23:55 hours (SGT)

About the European Society for Medical Oncology

ESMO is the leading professional organisation for medical oncology, with the overarching goal of improving outcomes for cancer patients everywhere. We are the society of reference for oncology education and information, and are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Founded in 1975, ESMO has European roots with a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience, and speaking with one voice for our discipline. Our education and information resources support an integrated multi-professional approach to cancer care, from a medical oncology perspective. We seek to erase boundaries in cancer care, whether between countries or specialities, and pursue our mission across oncology, worldwide.

The ESMO community brings together more than 12,000 oncology professionals from over 130 countries. Drawing on 40 years of experience and around 500 expert committee members, ESMO serves its members and the oncology community through: Cancer care is rapidly becoming more integrated and more specialised; whether their field is research, diagnosis, treatment, care, or advocacy, oncology professionals need to both build their specialist knowledge and connect with the best practitioners in other disciplines worldwide. ESMO membership makes this possible.

Please visit to learn more. Across Oncology. Worldwide.


Efficacy and safety of palbociclib plus fulvestrant in Asian women with hormone receptor-positive (HR+)/human epidermal growth factor-2 negative (HER2-) metastatic breast cancer (MBC) that progressed on prior endocrine therapy (ET)
J. Ro1, S.-A. Im2, N. Masuda3, Y.-H. Im4, K. Inoue5, Y. Rai6, R. Nakamura7, J.H. Kim8, K. Zhang9, C. Giorgetti10, P. Schnell11, C. Huang Bartlett12, H. Iwata13
1Center for Breast Cancer, National Cancer Center, Goyang, Korea, 2Medical Oncology, Seoul National University, Seoul, Korea, 3Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan, 4Professor, Division of Hematology/Medical Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea, 5Division of Breast Oncology, Saitama Cancer Center, Saitama, Japan, 6Principal of Sagara Hospital, Breast Surgery, Sagara Hospital, Hakuaikai Medical Corporation Sagara Hospital, Kagoshima, Japan, 7Division of Breast Surgery, Chiba Cancer Center Hospital, Chiba, Japan, 8Professor Division of Hematology/Medical Oncology, Seoul National University Bundang Hospital, Gyeonggi-do, Korea, 9Oncology Clinical Statistics, Pfizer Inc., San Diego, CA, USA, 10Clinical Oncology, Pfizer, Italy, Milan, Italy, 11Pfizer Inc., New York, NY, USA, 12Clinical Oncology, Pfizer Inc., New York, NY, USA, 13Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

Aim/Background: Endocrine resistance is a major clinical issue for patients (pts) with HR+/HER2- breast cancer. The standard of care (SOC) is to re-challenge with ET before switch to chemotherapy (CT). PALOMA3 assessed whether Palbociclib (P) + fulvestrant (F) prolonged progression-free survival (PFS) vs F + placebo (PLB) in pts with HR+/HER2- MBC whose disease had progressed on prior ET. Primary analysis showed median PFS of 9.2 vs 3.8 m (HR 0.42, P<0.001) in full population (Turner et al NEJM 2015). We present the efficacy and safety in Asian pts with longer follow-up.

Methods: In the Ph 3 PALOMA3 study, 521 pts were randomized 2:1 to P (125 mg/d oral [3 wks drug, 1 wk off]) + F (500 mg, SOC) or PLB + F. Pre-/perimenopausal pts also received goserelin. One previous line of CT for MBC was allowed. Safety assessments occurred at baseline and on D1 per cycle; blood counts every 2 wks for first 2 cycles and on D1 of subsequent cycles. Primary endpoint was investigator-assessed PFS. Secondary endpoints: overall survival, response assessment, patient-reported outcomes, safety. PALOMA3 enrolled pts in Korea and Japan.

Results: By March 2015, 105 Asian pts were randomized (P+F, 74; PLB+F, 31). Baseline characteristics were well balanced. Compared to non-Asians, median age was lower in Asians (52 vs 58 y) and more were pre/perimenopausal (42% vs 15%). 59% of Asian pts had visceral disease, 80% had documented endocrine responsiveness, 34% had 1 line of CT for MBC. Median PFS in Asian pts was not reached for P+F (95% CI 9.2-NR) and 5.8 m for PLB+F (3.5-9.5m) (HR 0.485 [95% CI 0.270-0.869], P=0.0065). Most common Grade 3/4 adverse events (AEs) in Asian pts were neutropenia (92%) and leucopenia (29%); febrile neutropenia occurred in 4.1% (P+F). No pt stopped P+F due to AEs. 51% of Asian pts had dose reduction due to AEs. 48% were on 100mg dose.

Conclusions: P+F improved PFS in Asians with HR+/HER2- MBC that progressed on prior ET. The safety profile was consistent with that seen in Non-Asians; neutropenia was the most common AE, and can be managed by dose reduction. P+F may be a reasonable therapeutic option in Asian pts. Clinical trial identification: Clinical Trial ID: NCT01942135

Disclosure: J. Ro: Dr. Ro has served as a consultant/advisor to Nippon Kayaku (NK) and has received travel support from Eisai
S.-A. Im: 2c. Receipt of Intellectual Property Rights / Patent Holder: NA 2d. Consulting Fees (e.g. advisory boards): Roche, Novartis, AstraZeneca 2f. Contracted Research (NOTE: Pls must provide disclosure in this category): AstraZeneca in 2014
N. Masuda: Fees for Non-CME Services Received Directry from Commercial Interest or their agents (speaker\'s Bureaus) Chugai, AstraZenaca Contracted Research Chugai, Novaltis, Pfizer, AstraZeneca, Lilly
K. Inoue: research funding Pfizer, Lily, Chugai, Taiho, Daiichi-Sankyo, Palexel
K. Zhang: Dr. Zhang is an employee of and owns stock in Pfizer Inc and receives stock options from Pfizer Inc.
C. Giorgetti: Dr. Giorgetti is an employee of, and owns stock in Pfizer Inc and receives stock options from Pfizer Inc.
P. Schnell: Dr. Schnell is an employee of, and owns stock in Pfizer Inc and receives stock options from Pfizer Inc.
C. Huang Bartlett: Dr. Huang Bartlett is an employee of and owns stock in Pfizer Inc and receives stock options from Pfizer Inc.
H. Iwata: Dr. Iwata has received honoraria from AstraZeneca, Eisai, Daiichi-Sankyo, Chugai, and Pfizer Inc.
All other authors have declared no conflicts of interest.

Keywords: palbociclib, metastatic breast cancer, Asian, endocrine resistance

European Society for Medical Oncology

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to