PALOMA-3 Trial

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone receptor positive, human epidermal growth factor 2-negative (HR+/HER2-) locally advanced, metastatic breast cancer (mBC) patients who have either progressed during or within 12 months of completion of hormone therapy: final analysis of the multicentre, double-blind, phase 3 randomised controlled trial 2.

This 3 minute animation provides an overview of the PALOMA-3 trial consisting of information such as study design, efficacy and quality of life (QoL). Once you have viewed the video and if you require further information please select the relevant tabs. 

Overall Survival

This 2 minute animation summarises the Overall Survival (OS) with Palbocilib + Fulvestrant in advanced breast cancer clincal publication. 

AI, aromatase inhibitor; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; LHRH, lutenising homone-releasing hormone.

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17:42539.

PP-IBR-GBR-1937. October 2019

PALOMA-3 study design2,3

PALOMA-3 was a phase III, double-blind, placebo-controlled, randomised study to assess the efficacy and safety of IBRANCE plus fulvestrant vs placebo plus fulvestrant in a population of women with HR+/HER2- advanced breast cancer who had progressed on ET.

PALOMA-3 baseline characteristics2

Baseline characteristics were generally balanced between treatment arms2

Adapted from Cristofanilli M, et al. Lancet Oncol. 2016;17:425-39.2

a Patients could have progressed during or within 12 months of completion of adjuvant therapy (21% of trial population), or during or within one month following treatment in the advanced setting (79% of trial population); progression could have occurred on any ET (tamoxifen, or steroidal or non-steroidal Al); one previous line of chemotherapy in advanced disease was allowed).2
b All pre- or peri-menopausal women received LHRH for at least 4 weeks prior to and for the duration of the trial.2
c According to RECIST criteria, version 1.1.2
d As per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2
e Data were unavailable for one patient in the ITT fulvestrant plus placebo group.2
f 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 early relapse; percentages are calculated on the basis of available data.2
g  Previous sensitivity to endocrine therapy was based on randomisation.2

CBR, clinical benefit rate (complete response, partial response or stable disease for >24 weeks); DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor positive; IM, intramuscular; ITT, intention-to-treat; LHRH, luteinising hormone-releasing hormone; mBC, metastatic breast cancer; OD, once daily; ORR, objective response rate (complete or partial response); OS, overall survival; PFS, progression-free survival; PO, by mouth; PROs, patient-reported outcomes; RECIST, Response Evaluation Criteria in Solid Tumors.

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17:42539.
  3. Cristofanilli M, et al. ASCO Annual Meeting, 2017, Chicago, IL, USA. Poster 1050.

PP-IBR-GBR-2151. December 2019

Efficacy

IBRANCE is effective in patients who have progressed on previous endocrine therapy (ET)2,3a

IBRANCE + fulvestrant delivers:2,3

  • More than double the mPFS compared with fulvestrant monotherapy (11.2 months with IBRANCE + fulvestrant vs 4.6 months with fulvestrant + placebo)
  • PFS benefit in patients with visceral and non-visceral metastases, as well as in the majority of other patient subgroups, vs fulvestrant + placebo
  • Statistically significantly improved ORR and CBR relative to fulvestrant + placebo
    • ORR: 19% with IBRANCE + fulvestrant vs 9% with fulvestrant + placebob
    • CBR: 67% with IBRANCE + fulvestrant vs 40% with fulvestrant + placebob

Progression-free survival3c

Adapted from Turner NC et al. N Engl J Med. 2018; 379:1926-363.

Multiple patient subgroups saw a mPFS benefit with IBRANCE + fulvestrant vs. placebo + fulvestrant1

IBRANCE + fulvestrant resulted in a PFS benefit across most patient subgroups, including those with visceral disease2d.

Subgroups defined by stratification factors and baseline characteristics (data cut-off: October 2015)1

P values were not reported for patient subgroups (ITT population, data cut-off: October 2015)1.

Adapted from the IBRANCE Summary of Product Characteristics1.

IBRANCE is the 1st CDK4/6 inhibitor with phase III overall survival data4

An overall survival analysis of PALOMA-3, with a median follow-up of 44.8 months, demonstrated:4

  • IBRANCE + fulvestrant improved overall survival vs placebo + fulvestrant4e

The difference did not reach statistical significance4e.

PALOMA-3: Median OS (ITT population)4e

Data cut-off: April 2018

 

IBRANCE has been shown to extend overall survival in ET-sensitive patients4

An exploratory analysis of overall survival in ET-sensitive patients in PALOMA-3 demonstrated:4

  • IBRANCE + fulvestrant offered longer overall survival than placebo + fulvestrant4f

Statistical significance could not be determined4fg.

PALOMA-3: Median OS in ET sensitive population 

Data cut-off: April 2018

Adapted from Turner NC et al. N Engl J Med 2018;379:192636.4

a Observed in a phase Ill, double-blind, placebo-controlled, randomised study of 521 women (pre-/peri and post-menopausal) with HR+/HER2- advanced breast cancer with relapse or progression on or after ET; patients were randomised 2:1 to receive IBRANCE plus fulvestrant or placebo plus fulvestrant; all pre or peri-menopausal women received LHRH for at least 4 weeks prior to and for the duration of the trial.2,3
b Secondary endpoint results are based on confirmed and unconfirmed responses according to RECIST 1.1.2
c According to investigator assessment (ITT population); primary endpoint of the PALOMA-3 trial.3
d In a population composed of 521 women (pre-/peri- and post-menopausal) with HR+/HER2- advanced breast cancer with relapse or progression on or after ET in the adjuvant setting; patients were randomised 2:1 to receive IBRANCE plus fulvestrant or placebo plus fulvestrant; all pre- or peri-menopausal women received LHRH for at least 4 weeks prior to and for the duration of the trial.2
e PALOMA-3 involved patients with HR+/HER2- locally advanced or mBC who had failed on prior ET. The primary endpoint in PALOMA-3 was investigator-assessed PFS in the ITT population, evaluated according to RECIST Version 1.1.2
f PALOMA-3 involved patients with HR+/HER2- locally advanced or mBC who had failed on prior ET. The primary endpoint in PALOMA-3 was investigator-assessed PFS in the ITT population, evaluated according to RECIST Version 1.1. The majority of patients were ET-sensitive, but some patients were resistant to prior ET.
g Exploratory analysis.4

Sensitivity to ET was defined as: documented clinical benefit (complete response, partial response, or stable disease for equal to or more than 24 weeks) from at least one previous ET regimen in the context of metastatic disease; or the receipt at least 24 months of adjuvant ET before recurrence.4

AI, aromatase inhibitor; CBR, clinical benefit response (complete response, partial response or stable disease for equal to or more than 24 weeks); CDK4/6, cyclin-dependent kinase; CI, confidence interval; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR, hazard ratio; HR+, hormone receptor-positive; ITT, intention to treat; LHRH, luteinising hormone-releasing hormone; mBC, metastatic breast cancer; mPFS, median progression-free survival; NICE, National Institute for Health and Care Excellence; ORR, objective response rate (complete or partial response); OS, overall survival; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RECIST, response evaluation criteria in solid tumours; SMC, Scottish Medicine Consortium.

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17:42539.
  3. Cristofanilli M, et al. ASCO Annual Meeting, 2017, Chicago, IL, USA. Poster 1050.
  4. Turner NC et al. N Engl J Med. 2018;379:192636.

PP-IBR-GBR-2420. June 2020

Best overall tumour response in the ITT population of PALOMA-32*

Data cut-off: October 2015

Secondary endpoint. Confirmed objective response defined as complete response or partial response according to RECIST V1.1.2
† PALOMA-3 involved patients with HR+/HER2- locally advanced or mBC who had failed on prior ET. The primary endpoint in PALOMA-3 was investigator-assessed PFS in the ITT population, evaluated according to RECIST V1.1.2 
‡ Confirmed partial response or complete response.1,2
§ Clinical benefit response plus partial response plus stable disease equal to or more than 24 weeks.1,2

AI, aromatase inhibitor; CBR, clinical benefit response; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; LHRH, lutenising homone-releasing hormone; mBC, metastatic breast cancer; ORR, objective response rate; RECIST, response evaluation criteria in solid tumours. 

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425439

PP-IBR-GBR-2137. December 2019

Quality of life

IBRANCE + fulvestrant maintained global QoL, improved emotional functioning and reduced and delayed pain symptoms vs placebo + fulvestrant3.

PALOMA-3 QoL results

PALOMA-3: Overall change in QLQ-C30 scales from baseline scores3*

Adapted from Turner NC, et al. Ann Oncol. 2018;29:669–803.

PALOMA-3: Time to deterioration in pain symptoms in the PRO-evaluable population4*

  • Significantly greater decrease in pain (-3.3 vs 2.0; p=0.0011)4
  • Consistent results also observed in patients with visceral disease4

Adapted from Harbeck et al. 2016;27(6):1047–544.

Results from an analysis of global QoL, functioning and symptoms data reported in the PALOMA-3 study4.
† Time to deterioration defined as time to ≥10 point increase from baseline. 131 (39.1%) patients in the IBRANCE + fulvestrant group had an event vs 83 (50%) in the placebo + fulvestrant group4
‡ Time to deterioration defined as time to ≥10 point decrease from baseline, with no subsequent increase above this threshold4.
# 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).2 Results shown here are for 199 patients4.
 

CI, confidence interval; FUL, fulvestrant; HR, hazard ratio; PLA, placebo; QoL, quality of life.

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17(4):425–439
  3. Turner NC, et al. Ann Oncol. 2018;29:669–80.
  4. Harbeck N, et al. Ann Oncol. 2016;27(6):1047–1054.

PP-IBR-GBR-1939. December 2019

Safety

Neutropenia of grade 3 or 4 occurred in 70% of the patients receiving palbociclib + fulvestrant and in none of the patients receiving placebo + fulvestrant, anaemia of grade 3 or 4 occurred in 4% and 2% of the patients, respectively, and thrombocytopenia of grade 3 or 4 occurred in 3% and none of the patients, respectively. Febrile neutropenia remained uncommon, occurring in 1% of the patients (3 of 345 patients) who received palbociclib + fulvestrant and in none of those who received placebo + fulvestrant. Nonhaematologic adverse events of grade 3 or 4 were also uncommon. Events of grade 3 or 4 that occurred at a frequency of more than 2% of the patients in the palbociclib + fulvestrant group were infections (in 5% of the patients in the palbociclib + fulvestrant group and in 3% of those in the placebo + fulvestrant group), fatigue (in 3% and 1%, respectively), and elevation in the aspartate aminotransferase level (in 3% and 2%)3.

Adverse events reported in PALOMA-3*

AEs from any cause that occurred in ≥10% of patients in the IBRANCE + fulvestant arm (as-treated population in PALOMA-3)The adverse-event profile of palbociclib–fulvestrant remained consistent with that in the primary analysis3.

Data cut-off: April 2018

Adapted from Turner NC, et al. N Eng J Med. 2018;379:1926–36. 

For full safety information and list of adverse events, please see the IBRANCE® Summary of Product Characteristics1.
Grading according to CTCAE 4.0 and MedDRA 18.0. Data are n (%) unless otherwise specified2.

* The overall safety profile of IBRANCE is based on pooled data from 872 patients who received IBRANCE in combination with ET (n=527 in combination with letrozole and n=345 in combination with fulvestrant) in randomised clinical studies in HR+/HER2- advanced or metastatic breast cancer1.

† Preferred Terms (PTs) are listed according to MedDRA 17.1. INFECTIONS includes all PTs that are part of the System Organ Class Infections and infestations. NEUTROPENIA includes the following PTs: Neutropenia, Neutrophil count decreased. LEUKOPENIA includes the following PTs: Leukopenia, White blood cell count decreased. ANAEMIA includes the following PTs: Anaemia, Haemoglobin decreased, Haematocrit decreased. THROMBOCYTOPENIA includes the following PTs: Thrombocytopenia, Platelet count decreased. STOMATITIS includes the following PTs: Aphthous stomatitis, Cheilitis, Glossitis, Glossodynia, Mouth ulceration, Mucosal inflammation, Oral pain, Oropharyngeal discomfort, Oropharyngeal pain, Stomatitis. RASH includes the following PTs: Rash, Rash maculo-papular, Rash pruritic, Rash erythematous, Rash papular, Dermatitis, Dermatitis acneiform, Toxic skin eruption1.

AE, adverse event, AI, aromatase inhibitor; AST, aspartate aminotransferase; CTCAE, common terminology for adverse events; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; LHRH, lutenising homone-releasing hormone; mBC, metastatic breast cancer, MedRA, medical dictionary for regulatory activity; PLA, placebo.

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Cristofanilli M, et al. Lancet Oncol. 2016;17:425-39.
  3. Turner NC, et al. N Engl J Med. 2018;379:1926–36. 

PP-IBR-GBR-2421. June 2020