Ibrance is indicated for the treatment of patients with hormone receptor positive, human epidermal growth factor receptor 2 negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy; or fulvestrant in patients with disease progression following endocrine therapy.1

Clinical efficacy across lines of therapy

​​​​​​​IBRANCE + letrozole in 1st line IBRANCE + fulvestrant in 1st line or later

PALOMA-3

PALOMA-3 was a randomised, double-blind, placebo-controlled, Phase III study that assessed the efficacy of IBRANCE in combination with fulvestrant vs placebo + fulvestrant in patients with HR+/HER2- ABC who had progressed on or after prior ET in the adjuvant or metastatic setting. Trial included 21% of patients who were treated in first line and/or pre-/peri-menopausal.2 One previous line of chemotherapy (CT) in advanced disease was allowed.2
Adapted from Cristofanilli M, et al. 2016.

*Defined as progression during or within 1 month after the end of prior ET in the context of metastatic disease or progression during or within 12 months after discontinuation of adjuvant ET. 21% of patients had not received prior treatment for their metastatic disease (1st line). Pre-/peri-menopausal patients received the LHRH agonist goserelin for at least 4 weeks prior to and for the duration of the trial.2 †Sensitivity to prior hormonal therapy was defined as documented clinical benefit (CR, PR, or SD ≥24 weeks) to ≥1 prior hormonal therapy regimen in the metastatic setting or ≥24 months of adjuvant hormonal therapy before recurrence.2 ‡Evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.2 #ORR was defined as confirmed complete response (CR) or partial response (PR).2 §CBR was defined as CR or PR or stable disease for ≥24 weeks.2
PALOMA-3 Baseline Characteristics
Adapted from Cristofanilli M, et al. 2016.2
Data cut-off date: March 16, 2015.
Data are number (%), unless otherwise specified. Because of rounding, some percentages do not total 100% when summed.
*Per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2 †Data were unavailable for one patient in the ITT fulvestrant + placebo group.2 ‡Disease-free interval was defined as time from diagnosis of primary breast cancer to first relapse in patients who received adjuvant therapy. Data for disease-free interval were available only for patients who were initially diagnosed with early breast cancer and then experienced disease relapse; percentages are calculated on the basis of available data.2 §Patients did not receive chemotherapy in the context of metastatic disease. #Previous sensitivity to endocrine therapy was based on randomisation.2  ¶For classification of receptor status (≥median of distribution, <median of distribution) the H-score was used. The median was calculated on the basis of the number of patients who were tested by the central laboratory (250 patients in the fulvestrant plus IBRANCE group and 130 patients in the fulvestrant plus placebo group).2
PALOMA-3 Inclusion and Exclusion Criteria

Adapted from Cristofanilli M, et al. 2016.2
*Pre-/peri-menopausal patients received the LHRH agonist goserelin for at least 4 weeks prior to and for the duration of the trial.2

ABC = advanced breast cancer; AI = aromatase inhibitor; CDK = cyclin-dependent kinase; CNS = central nervous system; CT = chemotherapy; ECOG = Eastern Cooperative Oncology Group; ET = endocrine therapy; FUL = fulvestrant; HR+/HER2- = hormone receptor-positive, human epidermal growth factor receptor 2-negative; IQR = interquartile range; ITT = intention to treat; LHRH = luteinising hormone-releasing hormone; mTOR = mechanistic target of rapamycin; n = number of patients; PFS = progression-free survival; PI3K = phosphoinositide 3-kinase; PLA = placebo; SD = standard deviation; RECIST = Response Evaluation Criteria In Solid Tumors.

Study design

References

  1. IBRANCE® (Palbociclib) Prescribing Information. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=12240. Accessed September 17, 2021.
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.
IBRANCE in combination with fulvestrant in 1st line or later doubled mPFS vs placebo + fulvestrant in patients with progression on/after ET in the PALOMA-3 trial*1,2
In a 2:1 randomised, double-blind, Phase III trial of women with HR+/HER2- mBC whose disease progressed following ET (N=521)2

Adapted from Cristofanilli M, et al. 20162 and IBRANCE SmPC.1
*Evaluated according to RECIST Version 1.1.2 †Data cut-off date: March 16, 2015. Updated non-prespecified analysis. Data cut-off date: October 23, 2015.

CI = confidence interval; ET = endocrine therapy; FUL = fulvestrant; HR+/HER2- = hormone receptor-positive/human epidermal growth factor receptor 2-negative;  HR = hazard ratio; mBC = metastatic breast cancer; mPFS = median progression-free survival; N/n = number of patients; PFS = progression-free survival;  PLA = placebo; RECIST = Response Evaluation Criteria in Solid Tumors; SmPC = Summary of Product Characteristics.

Primary endpoint: mPFS

Improved tumour response with IBRANCE + fulvestrant vs placebo + fulvestrant in 1st line or later (secondary endpoint)1

Adapted from IBRANCE SmPC.1

Data cut-off date: October 23, 2015.
*Defined as confirmed complete response or partial response.
2 †Defined as confirmed complete response or partial response or stable disease for ≥24 weeks.3

CBR = clinical benefit rate; FUL = fulvestrant; ITT = intention to treat; n = number of patients; ORR = objective response rate; PLA = placebo; SmPC = Summary of Product Characteristics.

Secondary endpoint: tumour control

The PALOMA-3 OS final analysis of IBRANCE + fulvestrant in 1st line or later demonstrated a numerical difference favouring IBRANCE + fulvestrant vs placebo + fulvestrant that did not reach statistical significance4

Adapted from Turner NC, et al. 2018.4
Data cut-off date: April 13, 2018.

The difference in median OS with IBRANCE + fulvestrant in 1st or later line (not statistically significant) was similar to the improvement in mPFS previously seen with the addition of IBRANCE to fulvestrant in PALOMA-34

Adapted from Turner NC, et al. 2018.4
*Data cut-off date: October 23, 2015. Data cut-off date: April 13, 2018.

CI = confidence interval; FUL = fulvestrant; HR = hazard ratio; mPFS = median progression-free survival; n = number of patients; OS = overall survival; PFS = progression-free survival; PLA = placebo; SmPC = Summary of Product Characteristics.

References

  1. IBRANCE® (Palbociclib) Prescribing Information. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=12240. Accessed September 17, 2021.
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.
  3. Turner NC, et al. Ann Oncol. 2018;29(3):669-680.
  4. Turner NC, et al. N Engl J Med. 2018;379(20):1926-1936.

Secondary endpoint: OS

Exploratory post-hoc analysis: time to subsequent therapy

In an exploratory post-hoc analysis of PALOMA-3, IBRANCE + fulvestrant in 1st or later line delayed median time to chemotherapy by 8.8 months vs placebo + fulvestrant2
Time to first subsequent CT from randomisation3
Adapted from Turner NC, et al. 2018.3
Data cut-off date: April 13, 2018.​​​​​​​
Delaying CT can help delay the impact of CT-associated AEs on the patient4
In this exploratory post-hoc analysis, using IBRANCE + fulvestrant in 1st or later line did not compromise the treatment benefit of subsequent therapies:2,3 
  • Patients were able to receive ET and CT as further treatment options following progression on IBRANCE + fulvestrant2
  • Median time from randomisation to end of immediate subsequent line of therapy delayed by 4.7 months with IBRANCE + fulvestrant vs placebo + fulvestrant3
AE = adverse event; CI = confidence interval;  CT = chemotherapy; ET = endocrine therapy; FUL = fulvestrant; HR = hazard ratio;  n = number of patients; PLA = placebo; TCT = time to chemotherapy.

References

  1. IBRANCE® (Palbociclib) Prescribing Information. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=12240. Accessed September 17, 2021.
  2. Turner NC, et al. N Engl J Med. 2018;379(20):1926-1936.
  3. Turner NC, et al. N Engl J Med. 2018;379(20):1926-1936. Supplementary appendix.
  4. Brufsky A. Clinical Medicine Insights: Oncology. 2015;9:137-147.

HR = hormone receptor; HER2 = human epidermal growth factor receptor 2; mPFS = median progression-free survival; OS = overall survival.

Reference

  1. IBRANCE® (Palbociclib) Prescribing Information. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=12240. Accessed September 17, 2021.

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