Patients with HR-positive, HER2-negative advanced or metastatic breast cancer who have had disease progression on or after prior adjuvant or metastatic endocrine therapy
PALOMA-3 was an international, randomized, double-blind, parallel group, multicenter study of IBRANCE plus fulvestrant versus placebo plus fulvestrant conducted in women with HR-positive, HER2-negative advanced breast cancer, regardless of their menopausal status, whose disease progressed on or after prior endocrine therapy. A total of 521 pre/postmenopausal women were randomized 2:1 to IBRANCE plus fulvestrant or placebo plus fulvestrant and stratified by documented sensitivity to prior hormonal therapy, menopausal status at study entry (pre/peri versus postmenopausal), and presence of visceral metastases. IBRANCE was given orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment. Pre/perimenopausal women were enrolled in the study and received the LHRH agonist goserelin for at least 4 weeks prior to and for the duration of PALOMA-3. Patients continued to receive assigned treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. The major efficacy outcome of the study was investigator-assessed PFS evaluated according to RECIST 1.1.
Patients enrolled in this study had a median age of 57 years (range 29 to 88). The majority of patients on study were White (74%), all patients had an ECOG PS of 0 or 1, and 80% were postmenopausal. All patients had received prior systemic therapy, and 75% of patients had received a previous chemotherapy regimen. Twenty-five percent of patients had received no prior therapy in the metastatic disease setting, 60% had visceral metastases, and 23% had bone only disease.
The results from the investigator-assessed PFS and final OS from PALOMA-3 are summarized in Table 9. The relevant Kaplan-Meier plots are shown in Figures 2 and 3, respectively. Consistent PFS results were observed across patient subgroups of disease site, sensitivity to prior hormonal therapy, and menopausal status. After a median follow-up time of 45 months, the final OS results were not statistically significant.
Table 9. Efficacy Results – PALOMA-3 | IBRANCE plus Fulvestrant | Placebo plus Fulvestrant |
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CI=confidence interval; ITT=Intent-to-Treat; N=number of patients; OS=overall survival; PFS=progression-free survival. |
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Progression-free survival for ITT (investigator assessment) | N=347 | N=174 |
Number of PFS events (%) | 145 (41.8) | 114 (65.5) |
Median PFS (months, 95% CI) | 9.5 (9.2, 11.0) | 4.6 (3.5, 5.6) |
Hazard ratio (95% CI) and p-value | 0.461 (0.360, 0.591), p<0.0001 |
Objective Response for patients with measurable disease (investigator assessment) | N=267 | N=138 |
Objective response rate* (%, 95% CI) | 24.6 (19.6, 30.2) | 10.9 (6.2, 17.3) |
Overall survival for ITT | N=347 | N=174 |
Number of OS events (%) | 201 (57.9) | 109 (62.6) |
Median OS (months, 95% CI) | 34.9 (28.8, 40.0) | 28.0 (23.6, 34.6) |
Hazard ratio (95% CI) and p-value | 0.814 (0.644, 1.029), p=0.0857†‡ |
Figure 2. Kaplan-Meier Plot of Progression-Free Survival – PALOMA-3 (Investigator Assessment, Intent-to-Treat Population) |
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| FUL=fulvestrant; PAL=palbociclib; PBO=placebo. | |
Figure 3. Kaplan-Meier Plot of Overall Survival (Intent-to-Treat Population) – PALOMA-3 |
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| FUL=fulvestrant; PAL=palbociclib; PBO=placebo. | |