PALOMA-3​

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone receptor positive, human epidermal growth factor 2-negaive (HR+/HER2-) metastatic breast cancer (mBC) that progressed on previous endocrine therapy: final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (Cristofanilli M, et al. 2016)2.​

Study Design and Patient Population​

PALOMA-3 was a randomised double blind, placebo-controlled, Phase III study that assessed the efficacy of IBRANCE® in combination with fulvestrant in a wide range of endocrine therapy (ET) -resistant patients, including 1st line (21%) and pre-/peri-menopausal (21%). Patients with extensive symptomatic visceral metastasis and at short-term risk of life-threatening complications were excluded from the trial. 2​

​Paloma-32​

paloma_3

Baseline Demographics

paloma_3_baseline_demographics

Adapted from Cristofanilli et al. 2016.2

*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 ​

† 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 complete response or progressive disease or stable disease for ≥24 weeks.2​

¿ Per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2 ​

§ Data was 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​

ECOG = Eastern Cooperative Oncology Group; ITT = intention to treat.​​

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.​

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

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone receptor positive, human epidermal growth factor 2-negaive (HR+/HER2-) metastatic breast cancer (mBC) that progressed on previous endocrine therapy: final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (Cristofanilli M, et al. 2016).​

Efficacy​

IBRANCE® + fulvestrant doubled median progression-free survival (mPFS) to 11.2 months  vs 4.6 with fulvestrant + placebo (HR=0.497; p<0.000001) in patients with progression on or after ET.1

paloma_3_efficacy

 

Adapted from Ibrance® Summary of Product Characteristics1

 

Sub-Group Analysis of mPFS*​

The mPFS improvements with IBRANCE® + fulvestrant were significant and consistent across multiple pre-defined sub-populations, regardless of site of disease, prior therapy and menopausal status.2

paloma_3_sub_group_analysis_mpfs

Adapted from Cristofanilli et al. 2016.2​

IBRANCE® was the first CDK4/6 inhibitor to report mature OS results from a phase III RCT 1-6.

The PALOMA-3 OS final analysis results demonstrated a positive trend favouring IBRANCE® + fulvestrant vs fulvestrant + placebo* that did not reach statistical significance1

paloma-3_os_ibrance_image

Turner NC et al. N Engl J Med, 2018;379:1926-19363

Best Overall Tumour Response ​

IBRANCE® + fulvestrant significantly improved tumour response rates: 25% objective response rate with IBRANCE® + fulvestrant vs 11% with fulvestrant alone (p=0.0012) and 64% clinical benefit rate# with IBRANCE® + fulvestrant vs 36% with fulvestrant alone (p<0.0001) in the measurable disease population.2​

paloma_3_best_overall_tumour

Adapted from Cristofanilli et al. 2016.2​

*Evaluated according to RECIST Version 1.1.2 ​

† 21% of patients who received IBRANCE® + fulvestrant were pre-/peri-menopausal (n=72).2 ​

‡ Visceral metastasis was defined as lung, liver, brain, pleural, or peritoneal involvement. 60% of patients who received IBRANCE® + fulvestrant presented with visceral metastasis (n=206).2

# 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

¿ Defined as confirmed complete response or partial response.2

§ Defined as complete response or partial response or stable disease ≥24 weeks.2 ​


CBR = clinical benefit response; FUL = fulvestrant; ITT = intention to treat; ORR = objective response rate; PLA = placebo. CI = confidence interval; ET = endocrine therapy; HR = hazard ratio; mPFS = median progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors.​​

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.​
  3. Turner NC et al. N Engl J Med, 2018;379:1926-1936

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

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone receptor positive, human epidermal growth factor 2-negaive (HR+/HER2-) metastatic breast cancer (mBC) that progressed on previous endocrine therapy: final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (Cristofanilli M, et al. 2016)2.​

Quality of Life Results​

IBRANCE® + fulvestrant maintained global quality of life, improved emotional functioning and reduced and delayed pain symptoms vs fulvestrant alone.3

Mean overall change from baseline on EORTC QLQ-C30*†3

paloma_3_qol_results

 

  • Significant delay in QoL deterioration (HR=0.641;​
    p=0.0065)‡3​

 

  • Consistent results also observed in patients with visceral disease#3​

Adapted from Harbeck et al. 2016 and Turner et al. 2015. 3,4​

Time to deterioration in pain symptoms*§3​

paloma_3_qol_results_2
  • Significantly greater decrease in pain ​
    (-3.3 vs 2.0; p=0.0011)‡3​

 

  • Consistent results also observed in patients with visceral disease#3​

 

Adapted from Harbeck et al. 2016. 3​

*Results from an analysis of global QoL, functioning and symptoms data reported in the PALOMA-3 study.3 ​
† Mean overall change from baseline on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Module (QLQ-C30). Higher scores (range 0–100) indicated better functioning/QoL or higher symptom severity.3 ​

‡ Time to deterioration defined as time to ≥10 point decrease from baseline, with no subsequent increase above this threshold.3

# Visceral metastasis was defined as lung, liver, brain, pleural, or peritoneal involvement. 60% of patients in PALOMA-3 who received IBRANCE® + fulvestrant presented with visceral metastasis (n=206).3 Results shown here are for 199 patients.

§ Time to deterioration defined as time to ≥10 point increase from baseline.3

HR = hazard ratio; QoL = quality of life.​​

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.​
  3. Harbeck N, et al. Ann Oncol. 2016;27(6):1047-1054.​
  4. Turner NC, et al. N Engl J Med. 2015; 16;373(3):209-219.​

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

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone receptor positive, human epidermal growth factor 2-negaive (HR+/HER2-) metastatic breast cancer (mBC) that progressed on previous endocrine therapy: final analysis of the multicentre, double-blind, phase 3 randomised controlled trial (Cristofanilli M, et al. 2016)2.​

Safety ​

The most common adverse events (Grade ≥3) with IBRANCE® + fulvestrant were neutropenia (65%), leukopenia (28%), anaemia (3%), thrombocytopenia (3%) and infections (3%).2 Febrile neutropenia was reported by 1.0% of patients.2 Neutropenia was effectively managed by dose modifications, without loss of efficacy.3 Discontinuation rates due to adverse events were low, with 96.0% of patients staying on IBRANCE® + fulvestrant.2

​Adverse events (≥10%) reported in PALOMA-3 (safety population)2

paloma_3_safety

Adapted from Cristofanilli et al. 2016.2

Grading according to CTCAE 4.0 and MedDRA 18.0. Data are n (%) unless otherwise specified.2​​

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

 

References​

  1. IBRANCE® Summary of Product Characteristics.​
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425-439.​
  3. Verma S, et al. Oncologist. 2016;21:1165-1175.​

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.