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Introduction
PALOMA-2 is an ongoing double-blind phase 3 study, suggested that palbociclib-letrozole significantly prolonged progression-free survival (PFS) vs. placebo-letrozole in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) at 23 months of follow-up.
Aim
To evaluate efficacy safety, and patient-reported outcome (PRO) results for the overall PALOMA-2 study population and across subgroups after
extended patient follow-up
Patient profile
Post-menopausal women with ER positive/HER2 negative ABC with no history of receiving systemic therapy for their advanced disease
Methods
Study drugs
Letrozole 2.5 mg/day continuously and either palbociclib (125 mg/day, 3 weeks on followed by 1 week-off of a 4-week cycle) or matching placebo.
End points
-
Primary endpoint: Investigator assessed PFS (first documented disease progression/death post randomization)
-
Secondary endpoints: Time to initiation of subsequent anticancer therapies (including chemotherapy), safety assessments and patient-reported outcomes (PROs)
Results
-
Median follow-up was ~38 months.
Figure 1: Investigator-assessed progression-free survival
Table 1: Investigator-assessed median PFS (months) in subgroup analysis
|
Sub-groups |
Palbociclib-Letrozole |
Placebo-Letrozole |
Hazard Ratio, 95% CI, P value |
|
Bone only |
36.2 |
11.2 |
0.406, 0.26-0.63, P<0.0001 |
|
Single disease site |
30.4 |
16.5 |
0.519, 0.34-0.75, P<0.0005 |
|
No prior endocrine therapy with non-visceral disease |
36.2 |
27.6 |
0.591, 0.38-0.92, P<0.01 |
Table 2: Median time (months) from randomization to initiation of subsequent anticancer therapies
|
Time from randomization to |
Palbociclib-Letrozole |
Placebo-Letrozole |
Hazard Ratio, 95% CI, P value |
|
First subsequent therapy |
28.0 |
17.7 |
0.64, 0.52-0.78, P<0.0001 |
|
Second subsequent therapy |
38.8 |
28.8 |
0.724, 0.58-0.90, P<0.005 |
|
First subsequent chemotherapy |
40.4 |
29.9 |
0.735, 0.59-0.92, P<0.005 |
-
No new safety signals were observed for palbociclib-letrozole group during the extended 15 months of follow-up.
-
Neutropenia was the most frequently reported any-grade AE with palbociclib-letrozole (81.8%) vs 6.3% with placebo letrozole
-
Treatment emergent serious AEs (SAEs) of any cause occurred in 23.6% of palbociclib-letrozole patients and 15.3% of placebo letrozole patients.
-
Infections were the most commonly reported SAE in both arms (5.2% and 4.1%, respectively).
-
Patient-reported HRQOL scores were comparable in both palbociclib-letrozole and placebo-letrozole.
Conclusion
-
Palbociclib-letrozole consistently improved PFS and substantially delayed the next line of therapies with no new safety signal.
-
This combination should be regarded as an important first-line therapy in ER+/HER2− ABC patients.
Reference
Breast Cancer Res Treat 2019;174:719-29.
