SINGAPORE—Data collected from Japanese and Korean participants in the global PALOMA3 trial provide evidence that combining palbociclib with fulvestrant is an effective strategy to overcome endocrine resistance in women with advanced breast cancer that is hormone receptor-positive (HR+) and HER2-negative (HER2–). The analysis of efficacy and safety of the combination therapy in an Asian population was presented at the European Society for Medical Oncology (EMSO) Asia 2015 Congress. The 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 patients with breast cancer, with demonstrated benefits in patients whose tumors express hormone receptors, 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, almost all patients with advanced disease develop resistance a median 10 months after first-line hormonal treatment, and a much shorter median time after second- or third-line hormonal treatments. Eventually, patients need to switch to the more toxic chemotherapy, explained coauthor Jungsil Ro, MD, PhD, of the Center for Breast Cancer at the National Cancer Center in Goyang, Korea.
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 pre- 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 randomly assigned to receive palbociclib plus fulvestrant (74 patients) or placebo plus fulvestrant (31 patients).
“For postmenopausal women, the study definitely showed positive results: progression-free survival more than doubled,” Ro said. Patients suffered from more adverse events in the palbociclib arm, specifically hematologic toxicity, which was easily managed.
“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 that included Asian patients 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,” said ESMO spokesperson, Fabrice André, MD, PhD, Institut de Cancérologie Gustave Roussy, Villejuif, France. “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.”
Ro explained that predictive biomarkers to select patients for palbociclib and fulvestrant combination therapy beyond HR+/HER2– subtype are still lacking.
On the basis of the impressive results from the phase II PALOMA-1 trial, the palbociclib plus letrozole combination was approved by US Food and Drug Administration (FDA) for the treatment of postmenopausal women with estrogen receptor-positive (ER+)/HER2– advanced breast cancer as initial endocrine-based therapy for their metastatic disease.