Editor's Note: For premenopausal patients with HR+/HER2- metastatic breast cancer (mBC), treatment choices are complex due to physiological characteristics, tumor properties, and treatment tolerance. Many patients receive chemotherapy early due to endocrine resistance and concerns about rapid tumor progression, with capecitabine being a commonly used regimen. At the 2024 ASCO conference, the latest updated survival results from the Young-PEARL randomized phase II study were presented. The study evaluated the safety and clinical anti-tumor efficacy of palbociclib combined with GnRHa and exemestane versus capecitabine in premenopausal HR+/HER2- mBC patients. Oncology Frontier interviewed the primary investigator, Professor Yeon Hee Park from Samsung Medical Center in Seoul, Korea, to discuss the study's background, methods, main results, and clinical significance. This comparative study provides significant insights into endocrine therapy for HR+/HER2- advanced breast cancer, offering a valuable alternative to traditional chemotherapy.The Young-PEARL study evaluated the combination of GnRH agonist with palbociclib and exemestane versus capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer (mBC). Key findings include:
- The combination treatment improved progression-free survival (PFS) with a median of 19.5 months compared to 14.0 months for capecitabine.
- No overall survival (OS) benefit was observed between the two treatment groups after a median follow-up of 54.0 months.
- The objective response rate (ORR) was similar for both groups at around 33%.
- The palbociclib group had a higher rate of grade 3 or higher treatment-related adverse events, mainly asymptomatic neutropenia.
The study showed a PFS benefit for the combination treatment without an OS advantage, and both treatments had a manageable safety profile.
Researcher Insights
Oncology Frontier: Dr. Park, thank you for joining us today. Could you start by summarizing the main findings of your recent study?
Dr. Yeon Hee Park: Thank you for having me. Our study compared the efficacy and safety of endocrine therapy with palbociclib plus exemestane and GnRH agonist versus capecitabine in premenopausal patients with ER-positive, HER2-negative metastatic breast cancer. The primary results were released in 2019, and this year we published the long-term overall survival results. We found that the primary endpoint of progression-free survival (PFS) was consistently maintained, showing significant benefit in the palbociclib plus exemestane plus endocrine arm.
Oncology Frontier: What were the overall survival results, and how do they compare between the two treatment arms?
Dr. Yeon Hee Park: The overall survival results were quite impressive. The palbociclib arm showed a median overall survival of 54.8 months, compared to 57.8 months for the capecitabine arm. While the survival rates are close, the progression-free survival and the consistency of the PFS benefit in the palbociclib arm highlight its effectiveness.
Oncology Frontier: Can you elaborate on the toxicity profiles observed in the study?
Dr. Yeon Hee Park: Certainly. The study showed that the palbociclib arm had manageable toxicity, primarily hematologic, which was not severe in most cases. On the other hand, the capecitabine arm exhibited different toxicity profiles, including diarrhea and hand-foot syndrome, which were also well managed over time. The addition of CDK4/6 inhibitors, like palbociclib, showed beneficial effects without introducing significant new toxicities.
Oncology Frontier: How do these findings impact the treatment landscape for premenopausal ER-positive, HER2-negative metastatic breast cancer patients?
Dr. Yeon Hee Park: These findings reinforce the use of palbociclib combined with endocrine therapy and GnRH agonists as a safe and effective treatment option for premenopausal patients. The study’s results align with those of the MONALEESA-7 trial, confirming the combination’s efficacy and safety. This provides a valuable alternative to cytotoxic chemotherapy, offering similar survival benefits with potentially better quality of life.
Oncology Frontier: What are the next steps for research in this area?
Dr. Yeon Hee Park: Future research will continue to explore the long-term benefits and potential combination therapies involving CDK4/6 inhibitors. There is also interest in investigating the role of these therapies in other patient subgroups and further understanding the mechanisms behind their efficacy and safety profiles. We aim to refine treatment protocols to maximize patient outcomes while minimizing side effects.
Professor Yeon Hee Park Professor, Chief Physician, Researcher, Doctoral Supervisor Director of Surgery, Samsung Medical Center, Seoul Deputy Director of Yixian Breast Cancer Hospital, Director of Breast Cancer Center, and Head of Breast Surgery Member of the ESO-ESMO International Consensus Panel for Young Breast Cancer Standing Committee Member and Deputy Secretary-General of the Breast Cancer Professional Committee of the Chinese Society of Clinical Oncology Standing Committee Member of the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association Standing Committee Member of the Tumor Molecular Medicine Professional Committee of the Chinese Anti-Cancer Association Chairman of the Breast Disease Branch of the Guangdong Medical Association Deputy Editor-in-Chief of the Chinese Journal of General Surgery and the Chinese Journal of Endocrine Surgery PhD in Surgery from the National University of Singapore, former lecturer at Dana Farber Cancer Center, Harvard University Has led multiple national key projects, including key projects of the National Natural Science Foundation and international cooperation key topics. He pioneered the application of liquid biopsy and immunotherapy in breast cancer and initiated and formulated China’s first expert consensus on the diagnosis and treatment of young breast cancer. In 2020, he was honored with the “National Doctor·Outstanding Model” title by People’s Daily. He specializes in the diagnosis, surgery, and comprehensive treatment of breast cancer, particularly high-difficulty breast-conserving surgery, individualized precision treatment of young breast cancer, and triple-negative breast cancer.
