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Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.
A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.
“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).
PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.
The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.
Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.
Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.
Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).
“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.
The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.
Taking into account all caveats inherent to analyses of subpopulations of large clinical trials (for example, invariably small sample size and multiplicity of testing), the data presented by Iwata et al. support the clinically meaningful efficacy of palbociclib for the end point of progression-free survival (PFS) in Asians. However, this report and others indicate that Asians have a higher risk of adverse events (including grade 3 and 4 neutropenia) despite preserved patient-reported outcomes and quality of life. The reasons for this have yet to be elucidated. In light of growing evidence of interethnic pharmacogenomic and safety discrepancies between Asian and non-Asian populations observed in recently published clinical trials and observational studies, there is a clear need for enhanced enrollment of Asian patients and other ethnic groups into clinical trials of new agents for the treatment of metastatic breast cancer.
Ricardo L.B. Costa, MD, and William J. Gradishar, MD, are with the Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. These comments are excerpted from an editorial accompanying the report by Dr. Iwata and his coauthors (J Glob Oncol. 2017 Apr 11. doi: 10.1200/JGO.2017.009936).
Taking into account all caveats inherent to analyses of subpopulations of large clinical trials (for example, invariably small sample size and multiplicity of testing), the data presented by Iwata et al. support the clinically meaningful efficacy of palbociclib for the end point of progression-free survival (PFS) in Asians. However, this report and others indicate that Asians have a higher risk of adverse events (including grade 3 and 4 neutropenia) despite preserved patient-reported outcomes and quality of life. The reasons for this have yet to be elucidated. In light of growing evidence of interethnic pharmacogenomic and safety discrepancies between Asian and non-Asian populations observed in recently published clinical trials and observational studies, there is a clear need for enhanced enrollment of Asian patients and other ethnic groups into clinical trials of new agents for the treatment of metastatic breast cancer.
Ricardo L.B. Costa, MD, and William J. Gradishar, MD, are with the Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. These comments are excerpted from an editorial accompanying the report by Dr. Iwata and his coauthors (J Glob Oncol. 2017 Apr 11. doi: 10.1200/JGO.2017.009936).
Taking into account all caveats inherent to analyses of subpopulations of large clinical trials (for example, invariably small sample size and multiplicity of testing), the data presented by Iwata et al. support the clinically meaningful efficacy of palbociclib for the end point of progression-free survival (PFS) in Asians. However, this report and others indicate that Asians have a higher risk of adverse events (including grade 3 and 4 neutropenia) despite preserved patient-reported outcomes and quality of life. The reasons for this have yet to be elucidated. In light of growing evidence of interethnic pharmacogenomic and safety discrepancies between Asian and non-Asian populations observed in recently published clinical trials and observational studies, there is a clear need for enhanced enrollment of Asian patients and other ethnic groups into clinical trials of new agents for the treatment of metastatic breast cancer.
Ricardo L.B. Costa, MD, and William J. Gradishar, MD, are with the Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago. These comments are excerpted from an editorial accompanying the report by Dr. Iwata and his coauthors (J Glob Oncol. 2017 Apr 11. doi: 10.1200/JGO.2017.009936).
Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.
A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.
“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).
PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.
The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.
Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.
Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.
Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).
“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.
The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.
Among Asian women with hormone receptor–positive/human epidermal growth factor receptor-2 (HER2)–negative metastatic breast cancer that is resistant to endocrine therapy, a combination of palbociclib (Ibrance) and fulvestrant (Faslodex) was associated with a significant improvement in progression-free survival (PFS), reported investigators from the PALOMA-3 trial.
A preplanned subgroup analysis of 102 pre- and postmenopausal women from Japan, South Korea, and Taiwan who were enrolled in the trial showed that median PFS for 71 women assigned to palbociclib and fulvestrant had not been reached at the trial end. In contrast, median PFS among 31 patients assigned to placebo and fulvestrant was 5.8 months (hazard ratio, 0.485; P = .0065), reported Hiroji Iwata, MD, PhD, of the Aichi Cancer Center Hospital in Nagoya, Japan, and his colleagues.
“Overall, palbociclib plus fulvestrant seems to be a reasonable treatment option in Asians with HR-positive/HER2-negative metastatic breast cancer that has progressed on prior endocrine therapy,” they wrote in the Journal of Global Oncology (2017 Apr 11. doi: 10.1200/JGO.2016.008318).
PALOMA-3 was a multinational randomized double-blind, placebo-controlled phase III trial comparing a combination of fulvestrant, a selective estrogen receptor downregulator, and palbociclib, a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) with fulvestrant plus placebo in 521 women with HR-positive/HER2-negative advanced breast cancer.
The trial was halted early for efficacy of the combination. The final overall analysis, published in April 2016 in The Lancet Oncology, showed that the combination significantly improved PFS, compared with fulvestrant and placebo, regardless of the patients’ degree of endocrine resistance, level of hormone receptor expression level, or PIK3CA mutational status.
Dr. Iwata and his associates noted that breast cancer is generally diagnosed at a younger age among Asian women (median, 45-50 years vs. 55-60 years among Western women) and that differences in genetic backgrounds may influence drug metabolism, resulting in potential differences in efficacy and adverse event profiles.
Among patients treated with palbociclib, the most common grade 3 or higher adverse events were neutropenia in 92%, compared with none in the placebo arm, and leukopenia in 29% vs. 0%. In contrast, grade 3/4 neutropenia occurred in 58% of non-Asian patients treated with the combination and 0.7% of non-Asian controls. Leukopenia rates were similar between Asian and non-Asian populations, however.
Comparisons of mean trough concentrations across subgroups showed that palbociclib exposures among Asians and non-Asians were similar. Patient reported outcomes were also similar between the groups, except for significantly more dyspnea among patients who received palbociclib (P = .05).
“This study adds to the limited body of literature assessing a CDK4/6 inhibitor in Asians and represents the largest patient experience with palbociclib in Asians. The present findings show that palbociclib plus fulvestrant improved PFS in Asians with HR-positive/HER2-negative [metastatic breast cancer] who experienced progression on prior endocrine therapy and that the safety profile of palbociclib plus fulvestrant in Asians was generally consistent with that observed in non-Asians. Together, these findings suggest that palbociclib is beneficial in patients who have not previously received endocrine therapy and in Asians and non-Asians who experienced relapse or progression during prior endocrine therapy,” they wrote.
The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.
FROM THE JOURNAL OF GLOBAL ONCOLOGY
Key clinical point: Asian patients with HR+/HER2– metastatic breast cancer derive the same benefits from palbociclib and fulvestrant as non-Asian patients.
Major finding: Median PFS was 5.8 months for patients treated with fulvestrant plus placebo, vs. not reached for patients treated with fulvestrant plus palbociclib.
Data source: Subanalysis of data on 102 Asian patients in the PALOMA-3 randomized, double-blind, placebo-controlled trial.
Disclosures: The PALOMA-3 trial was supported by Pfizer. Dr. Iwata disclosed consultations with Chugai Pharma, Eisai, and AstraZeneca. Several coauthors are Pfizer employees and shareholders.