NCC Announces Positive Top-Line Results of Japan-led international Investigator-Initiated Registration-Directed Phase III Study Evaluating Palbociclib Plus Tamoxifen in Patients with Hormone Receptor-positive, HER2-negative Advanced or Metastatic Breast Cancer (NCCH1607/PATHWAY trial)

20 Feb. 2023
National Cancer Center Japan
In Jaspanese

Highlights

• NCCH1607/PATHWAY trial met its primary endpoint of demonstrating an improvement in progression-free survival (PFS) for the combination of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib in combination with tamoxifen in pre/post-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer.
  
  

The National Cancer Center Hospital (President: Hitoshi Nakagama, Director: Kazuaki Shimada, Tokyo, Japan) today announced that the Phase 3 trial (Study ID: NCCH1607/PATHWAY) met its primary endpoint of demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the combination of palbociclib plus tamoxifen compared with placebo plus tamoxifen in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer. We believe the results of this trial has a high impact for premenopausal breast cancer patients, for which a large percentage of patients exist in Asian region with fewer treatment options. Detailed efficacy and safety results will be submitted for presentation at future international academic conference.

About palbociclib

Palbociclib, the drug used in this trial, is a novel oral molecular target drug that inhibits CDK 4/6. CDK 4/6 has the primary role of adjusting of the cell cycle, and causes cell proliferation. It is believed that palbociclib selectively inhibits CDK 4 and 6, halting progression of the cell cycle and thus suppressing tumor proliferation.

Palbociclib has been approved in more than 100 countries including the US, and was approved in Japan, based on the results of PALOMA-2 and PALOMA-3, palbociclib 25 mg and 125 mg capsules and tablets  (Brand name: IBRANCE capsules 25 mg, 125 mg, and IBRANCE tablets 25 mg, 125 mg) were approved for the indication of "hormone receptor-positive and HER2-negative, inoperable or recurrent breast cancer" on 27 September 2017 and 23 January 2020, respectively.  The efficacy and safety in combination with tamoxifen had not been established.

Background

Breast cancer is the most common cancer in women worldwide. HR+ breast cancer may use hormones to accelerate their growth. Endocrine therapy blocks the production of hormones or interferes effects of hormones on breast cancer cells. Endocrine therapy is recommended for patients with HR+/ HER2- advanced or metastatic breast cancer. Depending on several factors such as menopausal status, history of treatment, age, and extent of the cancer, the appropriate endocrine therapy is selected for each patient. Palbociclib in combination with tamoxifen is not approved for use at this time.

About the PATHWAY trial

 NCCH1607/PATHWAY trial is an investigator-initiated registration-directed clinical trial (IIRDT) of the CDK 4/6 inhibitor palbociclib in 184 HR+/HER2- advanced or metastatic breast cancer patients, including premenopausal, perimenopausal and postmenopausal status. This NCCH-led IIRDT has been conducted in the Asian region with participation of 12 sites in Japan, 6 in South Korea, 3 in Taiwan and 2 in Singapore. PATHWAY trial is a clinical research collaboration with Pfizer Inc., a research funder and a study drug provider. It has been conducted as an IIRDT in Japan, and as an international clinical trial with the NCCH as the regulatory sponsor in other Asian countries. A positive result of the PATHWAY trial would provide a robust evidence of palbociclib with an additional endocrine therapy partner, and could be the basis for discussions with regulators.

 Facilitating international collaborative research initiated by academic institutions in Japan and ATLAS project:

In recent years, the number of industry-sponsored global clinical trials is increasing, anticipating its advantage of recruitment speed and accelerating treatment development in broader area. Global clinical trials are also important for academia for establishing new standard cancer treatment earlier. While many academic global clinical trials have been conducted by some research groups in the US and Europe, some Japanese institutions come to participate in overseas-led global clinical trials. However, a Japanese investigator-led global clinical trial has rarely been conducted due to the language (English) barrier, personnel shortage, or limited research budget.

NCCH has actively been conducting many domestic IIRDTs for diseases of which pharmaceutical manufacturers are having difficulty in development of new therapies, while there has been a strong need of its establishment. In 2016, among all the Clinical Research Core Hospitals in Japan, NCCH and Osaka University Hospital have been selected by the AMED (Japan Agency for Medical Research and Development) as the Global Clinical Trials Core Center¹⁾, focused on the reinforcement of facilitating international clinical trials in Japan. NCCH therefore initiated this first global IIRDT, taking advantage of its experience and support function for clinical trials.

Currently, NCCH is making the particular effort to facilitate the ATLAS (Asian clinical TriaLs network for cAncerS) project²⁾, which will establish a clinical research network across Asia, including not only the participating regions of PATHWAY trial but also some ASEAN countries. Based on the experience and network gained from the PATHWAY trial, NCCH continues to expand the research network through the ATLAS project pursuing an advancement of new treatment development in Asia.

 

• This project has been transferred to one of the programs of the AMED Project for Comprehensive Program for Improving Infrastructure to Promote Clinical Application of Innovative Medical Seeds since FY2017.
• This project is funded by AMED as the Project Promoting Clinical Trials for Development of New Drugs　(Project to Create a Clinical Research and Trial Network in the Asian Region)

 

Sites participating in this trial

• Japan: National Cancer Center Hospital / Hokkaido Cancer Center / Chiba Cancer Center/ National Cancer Center Hospital East / Toranomon Hospital / Kanagawa Cancer Center / Aichi Cancer Center Hospital / Osaka National Hospital / Kindai University Hospital / Hyogo Cancer Center / Shikoku Cancer Center / Kyushu Cancer Center
• South Korea: Severance Hospital, Yonsei University Health System / Seoul National University Hospital / Seoul National University Bundang Hospital / Asan Medical Center / National Cancer Center (Korea) / Ajou University Hospital
• Taiwan: National Taiwan University Hospital / Sun Yat-Sen Cancer Center / Taipei Veterans General Hospital
• Singapore: National Cancer Centre Singapore / National University Hospital

Details of this trial

• Trial title: Asian, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tamoxifen With or Without Palbociclib +- Goserelin in Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer (NCCH1607, PATHWAY trial)
• 　 Study Chair: Kan Yonemori, MD. PhD,
• 　 UMIN trial ID: UMIN000030816
• 　 ClinicalTrials.gov registration number: NCT03423199

　Please refer the following for details of this trial.

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034267(linked at extenal site)
https://clinicaltrials.gov/ct2/show/NCT03423199(linked at extenal site)

Contact information

• About the clinical trial

Tomomi Hata
International Trial Management Section, Clinical Trial Management Division, Clinical Research Support Office, National Cancer Center Hospital
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Phone: +81-3-3547-5201 (ex 6137)
E-mail: NCCH1607_office●ml.res.ncc.go.jp

• Press and media enquiries

Publicity Planning Office, Strategic Planning Bureau, National Cancer Center
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Phone: +81-3-3542-2511
E-mail：ncc-admin●ncc.go.jp