Clinical efficacy across lines of therapy

PALOMA-2

Study design
PALOMA-2 was a randomised, double-blind, placebo-controlled, Phase III study that assessed the safety and efficacy of IBRANCE® in combination with letrozole as 1st line treatment vs placebo + letrozole in a wide range of aromatase inhibitor (AI) sensitive post-menopausal patients with ER+/HER2- ABC, including those with bone-only disease (23.2% ) and visceral disease (48.2%).2
 
Adapted from Finn RS, et al. 2016.2
*Evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.2  ORR was defined as confirmed complete response or partial response.2  CBR was defined as confirmed complete response, partial response, or stable disease for ≥24 weeks.2
PALOMA-2 Baseline Characteristics
Adapted from Finn RS, et al. 2016.2
Data cut-off date: February 26, 2016. Some percentages do not sum to 100 because of rounding.
*Disease-free interval was defined as the time from adjuvant or neoadjuvant therapy to recurrence. Newly metastatic disease applies to patients who had not received any prior systemic therapy, for whom a determination of disease-free interval was not possible.2 †Patients who received anastrozole or letrozole as a component of their adjuvant or neoadjuvant therapy were excluded from the study if they had disease progression while receiving the therapy or within 12 months after completing the therapy.2
PALOMA-2 Inclusion and Exclusion Criteria
Adapted from Finn RS, et al. 2016.2
ABC = advanced breast cancer; CNS = central nervous system; DFI = disease-free interval; ECOG = Eastern Cooperative Oncology Group;
ER+/HER2- = estrogen receptor-positive, human epidermal growth factor receptor 2-negative; LET = letrozole;
= number of patients; PFS = progression-free survival; PLA = placebo; QTc = QT interval corrected for heart rate.
 
Primary endpoint: mPFS
IBRANCE® in combination with letrozole delivered >2 years mPFS in 1st line in the PALOMA-2 trial,2,3 with 37 months of clinical trial follow-up*3
In a 2:1 randomised, double-blind, Phase III trial of post-menopausal women with ER+/HER2- mBC (N=666)2
clinical-efficacy-across-lines-therapy
At the time of final analysis of PFS, OS data were not mature. Patients will continue to be followed for the final analysis.
Adapted from Finn RS, et al. 2016.2 and Rugo H, et al. 2019.3
*Evaluated according to RECIST Version 1.1.2 Data cut-off date: February 26, 2016.2 Data cut-off date: May 31, 2017. Updated follow-up of the primary analysis of PALOMA-2: 37.6 months in the IBRANCE + LET arm.3
CI = confidence interval; ER+/HER2- mBC = estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer; HR = hazard ratio; LET = letrozole; mPFS = median progression-free survival; N/n = number of patients; NE = not estimable; OS = overall survival; PLA = placebo; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors.
ibrance-hcp-portal_rwe-update
Secondary endpoint: tumour control
Improved tumour response in 1st line with IBRANCE® + letrozole vs placebo + letrozole (secondary endpoint)2
clinical-efficacy-across-lines-therapy
Adapted from Finn RS, et al. 2016.2
Data cut-off date: February 26, 2016.
*Defined as confirmed complete response or partial response.2 Defined as confirmed complete response, partial response, or stable disease for ≥24 weeks.2
CBR = clinical benefit rate; ITT = intention-to-treat; LET = letrozole; ORR = objective response rate; N/n = number of patients; PLA = placebo.
 
Exploratory post-hoc analysis: time to subsequent therapy
In an exploratory post-hoc analysis of PALOMA-2, 1st line IBRANCE® + letrozole delayed median time to chemotherapy by 10.5 months vs placebo + letrozole*3
 
Adapted from Rugo H, et al. 2019.3
Data cut-off date: May 31, 2017.
*Updated follow-up of the primary analysis of PALOMA-2: 37.6 months in the IBRANCE® + LET arm.3

 

Delaying CT can help delay the impact of CT-associated AEs on the patient5

 

In this exploratory post-hoc analysis, using IBRANCE® + letrozole in 1st line did not compromise the treatment benefit of subsequent therapies:
  • Patients were able to receive ET and CT as further treatment options following progression on IBRANCE® + letrozole3,6
  • Median time from randomisation to start of the 1st and 2nd subsequent anticancer therapies delayed by 10 months with IBRANCE® + letrozole vs placebo + letrozole3
AE = adverse event; CI = confidence interval; CT = chemotherapy; ET = endocrine therapy; HR = hazard ratio; LET = letrozole; 
= number of patients; PLA = placebo.
References

1. IBRANCE® Summary of Product Characteristics
2. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.
3. Rugo H, et al. Breast Cancer Res Treat. 2019;174(3):719-729.
4. Turner NC, et al. Ann Oncol. 2018;29(3):669-680.
5. Brufsky A, Clinical Medicine Insights: Oncology. 2015;9:137-147.
6. Rugo HS, et al. Breast Cancer Res Treat. 2019;174(3):719-729. Supplementary Appendix.

 

 

PP-IBR-IRL-0373 Date of Preparation January 2020