PALOMA-2​

Primary results from a Phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with estrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (Finn RS et al. 2016)2​

Study design and patient population​

​PALOMA-2 was a randomised, double-blind, placebo-controlled, Phase III efficacy study that assessed the safety and efficacy of IBRANCE® in combination with letrozole as 1st line treatment in a wide range of aromatase inhibitor (AI)- sensitive post-menopausal patients, including those with bone-only disease (23.2% ) and visceral disease (48.2%).2 Patients with advanced, symptomatic, visceral spread at risk of life threatening complication in the short term were excluded from the trial. 2​

​PALOMA-2 2​

paloma_2

Baseline Demographics

paloma_2_baseline_demographics

Adapted from Finn et al. 2016.2​

​*Evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.2

† Defined as confirmed complete response or partial response.2 ​

‡ Defined as confirmed complete response, partial response, or stable disease for ≥24 weeks.2​

¿ 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​

ECOG = Eastern Cooperative Oncology Group. ​​

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.​

PP-IBR-IRL-0288
Date of preparation: March 2020

Primary results from a Phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with estrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (Finn RS et al. 2016)2

Efficacy

In the PALOMA-2 trial IBRANCE® + letrozole delivered >2 years mPFS in 1st line,2,4 with 37 months of clinical trial follow-up.*4 In a 2:1 randomised, double-blind, Phase III trial of post-menopausal women with ER+/HER2- mBC (N=666)2

Adapted from IBRANCE® Summary of Product Characteristics1

*Evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.2

Sub Group Analysis of mPFS*

The mPFS improvements with IBRANCE® + letrozole were significant and consistent across all 1st line patient segments.2

paloma_2_sub_group_analysis_mpfs

 

Best Overall Tumour Response

1st line IBRANCE® + letrozole significantly improved tumour response rates: 55.3% objective response rate¿ with IBRANCE® + letrozole vs 44.4% with letrozole alone (p=0.03) and 84.3% clinical benefit rate‡ with IBRANCE® + letrozole vs 70.8% with letrozole alone (p<0.001) in the measurable disease population.2

*Evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.2

† Length of disease-free interval on or after prior adjuvant endocrine treatment2

Adapted from Finn et al. 2016.2

¿ Defined as confirmed complete response or partial response.2

‡ Defined as confirmed complete response, partial response, or stable disease for ≥24 weeks.2

LET = letrozole; mPFS = median progression-free survival; PLA = placebo; RECIST = Response Evaluation Criteria In Solid Tumors. CBR = clinical benefit response; ITT = intention to treat; ORR = objective response rate

References

  1. IBRANCE® Summary of Product Characteristics.
  2. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.
  3. Rugo et al. BCRT 2019
  4. Rugo H, et al. Breast Cancer Res Treat. 2019; 174(3):719-729.

PP-IBR-IRL-0288
Date of preparation: March 2020

Primary results from a Phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with estrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (Finn RS et al. 2016)2.​​

QOL Results​

1st line IBRANCE® + letrozole maintained health-related quality of life with no significant difference vs letrozole alone – even with a longer treatment duration (~6 months more) – in overall change from baseline for all domains of the Functional Assessment of Cancer Therapy-Breast questionnaire (FACT-B), including physical, social/family, emotional and functioning well-being.3​

Mean overall change from baseline on FACT-B*†3​

paloma_2_qol_results

*Results from an analysis of PROs for HRQoL in the PALOMA-2 study. PROs were assessed using the FACT-B questionnaire. FACT-B includes FACT-G and the BCS. FACT-G is a 27-item questionnaire divided into 4 domains: PWB, SWB, EWB, and FWB, rated on a Likert scale from 0-4, where 0 = not at all and 4 = very much. Subscale scores were used to derive 3 assessment outcomes: FACT-B total score, FACT-G total score, and FACT-B TOI, calculated as FACT-B total score = PWB + SWB + EWB + FWB + BCS; FACT-G total score = PWB + SWB + EWB + FWB and FACT-B TOI score = PWB + FWB + BCS.  A higher score indicates a better QoL. 3 ​
Based on repeated measures mixed-effects model.3​

AI = aromatase inhibitor; BCS = Breast Cancer Subscale; EWB = emotional well-being; FACT-B = Functional Assessment of Cancer Therapy – Breast; FACT-G = Fact-General; FWB = functional well-being; HRQoL = health-related quality of life; PWB = physical well-being; QoL = quality of life; PRO = patient-reported outcomes; SWB = social/family well-being; TOI = Trial Outcome Index.​

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. Annals of Oncology 2018; 29: 888-894. ​

PP-IBR-IRL-0288
Date of preparation: March 2020

Primary results from a Phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with estrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (Finn RS et al. 2016)2.​​

Safety​

The most common adverse events (Grade ≥3) with IBRANCE® + letrozole were neutropenia (66.5%), leukopenia (24.8%), anaemia (5.4%) and fatigue (1.8%). Febrile neutropenia was reported by 1.8% of patients. Neutropenia was successfully managed with appropriate supportive care and dose reductions. Discontinuation  rates due to adverse events were low, with 90.3% of patients staying on IBRANCE® + letrozole.2​

​Adverse events (≥10% ) reported in PALOMA-2 (all causality)2​

paloma_2_safety

Adapted from Finn et al. 2016.2

 

Grading according to CTCAE 4.0.​

*Categorised according to the MedDRA preferred terms.2 ​
† Febrile neutropenia was reported in 1.8% of patients in the IBRANCE® + letrozole group and in no patients in the placebo + letrozole group.2 ​
‡ In the IBRANCE® + letrozole group, 30.2% of patients had Grade 1 alopecia and 2.7% had Grade 2. In the placebo + letrozole group, 14.9% of patients had Grade 1 alopecia and 0.9% had Grade 2.2​

CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities.​​

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Finn RS, et al. N Engl J Med. 2016;375(20):1925-1936.​

 

PP-IBR-IRL-0288
Date of preparation: March 2020

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.