IBRANCE® palbociclib PALOMA-2 trial

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

This three-minute animation provides an overview of the PALOMA-2 trial. This covers various information such as the study design, efficacy and quality of life. If you require additional information after viewing the animation, please select the relevant tabs. 

AI, aromatase inhibitor; ER+, oestrogen receptor-positive; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+ hormone receptor-positive; LHRH, luteinising hormone-releasing hormone; mBC, metastatic breast cancer; 

References:

  1. IBRANCE® Summary of Product Characteristics.
  2. Finn RS, et al. N Engl J Med. 2016;375:1925-–936.
  3. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.

PP-IBR-GBR-2209. January 2020

Study design and patient population2

PALOMA-2 was a randomised, double-blind, placebo-controlled, phase III study that assessed the safety and efficacy of IBRANCE plus letrozole vs placebo plus letrozole as 1st line treatment in a wide range of AI sensitive post-menopausal patients, including those with bone-only disease (23.2%) and visceral disease (48.2%). Patients with advanced, symptomatic, visceral spread at the risk of life threatening complication in the short term were excluded from the trial3.

PALOMA-2 baseline characteristics3

Values are n (%) unless otherwise noted. Adapted from Rugo HS, el al. Breast Cancer Res Treat. 2019;174.719-293.

*Patients were not eligible if they had relapsed on a non-steroidal AI during or within 12 months of completing adjuvant therapy.2

According to RECIST criteria, version 1.12

This is defined as the time from (neo)adjuvant therapy to recurrence – the percentage is based on the number of patients who received (neo)adjuvant therapy3.

§Patients who progressed while on or within 12 months from completion of prior letrozole or anastrozole were excluded from the study3.

AI, aromatase inhibitor; CBR, clinical benefit rate (complete response, partial response or stable disease for >24 weeks); DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ER, oestrogen receptor; HER2-, human epidermal growth factor receptor 2-negative; 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; SD, standard deviation. 

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Finn RS, et al. N Engl J Med. 2016;375:1925–1936.
  3. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.

PP-IBR-GBR-2209. January 2020

Efficacy2

1st line IBRANCE + letrozole achieved 27.6 months median progression free survival (mPFS) vs. 14.5 months with letrozole + placebo (HR: 0.56 (95% Cl: 0.46-0.69)3a.

Median follow-up was 37.6 months in the IBRANCE + letrozole arm and 37.3 months in the placebo + letrozole arm3.

 

Median progression-free survival3ab

Patient subgroups

IBRANCE + letrozole resulted in a PFS benefit across all patient subgroups in the PALOMA-2 trial, including those with visceral disease3a.

Investigator-assessed PFS overall and across subgroups in PALOMA-2 (ITT population)3a

Adapted from Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719-293.

Data cut-off: May 2017

Subgroup analyses by baseline characteristics were pre-specified.

* In a population of post-menopausal women with ER+/HER2- locally advanced or metastatic breast cancer who had received no prior systemic treatment for their advanced disease.2

† 1-sided P-value from the log rank test.3

‡ Per tumour site.3

§ In this analysis, the protocol-defined disease-free interval is equivalent to TFI and refers to TFI since completion of prior (neo)adjuvant therapy and onset

of metastatic disease or disease recurrence.3

‖ A few patients initially enrolled into the trial as having measurable disease were later found to have nonmeasurable

disease beyond bone-only disease.3

Patients with visceral disease

The PALOMA-2 and PALOMA-3 clinical trials involved women with HR+/HER2-locally advanced or metastatic breast cancer1,4. Both trials included patients with and without visceral metastases4.

Women in PALOMA-2 had not yet received ET for advanced disease, whereas women in PALOMA-3 had received ET for advanced disease and progressed1,4.

Outcomes with IBRANCE in patients with visceral disease1,3,4

Delayed time to chemotherapy

In PALOMA-2, the median time to first-line subsequent chemotherapy was 40.4 months for the IBRANCE + letrozole arm vs 29.9 months for the placebo + letrozole arm3.

Median time from randomisation to first subsequent chemotherapy (ITT population)3

Adapted from Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719-293.

a Phase lll, double-blind, placebo-controlled, randomised study of a population composed of 666 post-menopausal women with ER+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease; patients were randomised 2:1 to receive IBRANCE plus letrozole or placebo plus letrozole2.

b According to investigator assessment (ITT population); primary endpoint of the PALOMA-2 trial2.

c 1-sided P value from the log-rank test3

d Per tumour site3.

e In this analysis, the protocol-defined disease-free interval is equivalent to TFI and refers to TFI since completion of prior (neo)adjuvant therapy and onset of metastatic disease or disease recurrence3.

f A few patients initially enrolled into the trial as having measurable disease were later found to have non-measurable disease beyond bone-only disease3.

g Data cut-off: May 20173.

h Data cut-off: October 20154.

i Objective responses are based on confirmed and unconfirmed responses according to RECIST 1.11.

j Data cut-off: February 20164.

AI, aromatase inhibitor; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; EORTC OLO-C30, European Organisation for Research and Treatment of Cancer quality of life questionnaire; ER+, oestrogen receptor-positive; ET, endocrine therapy; FACT-B, Functional Assessment of Cancer Therapy-Breast; HER2-, human epidermal growth factor receptor 2-negative; HR, hazard ratio; HR+, hormone receptor-positive; IA, investigator assessed; ITT, intention-to-treat; LET, letrozole; mBC, metastatic breast cancer; mPFS, median progression free survival; mTTR, median time to response; NE, not estimable; OR, odds ratio; ORR, objective response rate; QoL, quality of life; PFS, progression-free survival; TFI, treatment-free interval; TTD, time to deterioration.

References:

  1. IBRANCE® Summary of Product Characteristics.
  2. Finn RS, et al. N Engl J Med. 2016;375:1925–36.
  3. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.
  4. Turner NC, et al. Ann-Oncol. 2018;29:669–80

PP-IBR-GBR-2209. January 2020

Tumour response

IBRANCE + letrozole resulted in a significant improvement in CBR and a trend towards improved ORR vs letrozole + placebo1*.

Response rates in the ITT population1,2†‡

Adapted from Finn RS, et al. N Engl J Med. 2016;375:1925–362.

In a population of post-menopausal women with ER+/HER2- locally advanced or metastatic breast cancer who had received no prior systemic treatment for their advanced disease2.

† Clinical benefit response comprises of complete response, partial response or stable disease for ≥24 weeks2.

‡ Secondary endpoints results are based on confirmed and unconfirmed responses according to RECIST 1.11.

CBR, clinical benefit response; CI, confidence interval: ER+, oestrogen receptor-positive: ET, endocrine therapy: HER2-, human epidermal growth factor receptor 2-negative; ITT, intention-to-treat: OD, odds ratio; ORR, objective response rate (complete or partial response).

References:

  1. IBRANCE® Summary of Product Characteristics
  2. Finn RS, et al. N Engl J Med. 2016;375:1925-1936.
  3. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.

PP-IBR-GBR-2209. January 2020

Quality of life

The PALOMA-2 study shows that you can offer your patients efficacy without compromising QoL with IBRANCE in combination with letrozole4.

A post-hoc analysis of median TTD in FACT-B  scores showed a positive trend favouring IBRANCE + letrozole vs placebo + letrozole (HR: 0.883; P=0.1900)4.

The difference did not reach statistical significance4.

TTD in FACT-B scores in the PALOMA-2 overall population4*

Adapted from Rugo HS, et al. Ann Oncol. 2018;29:888-94.4

* In a population of post-menopausal women with ER+/HER2- locally advanced or metastatic breast cancer who had received no prior systemic treatment for their advanced disease2.

† FACT-B is a 37-item self-reporting instrument containing the 27-question FACT-G survey and a 10-question breast cancer additional concerns scale. A higher score in any FACT-B assessment indicates better QoL. TTD for FACT-B was defined as the duration between baseline and first occurrence of a decrease of ≥7 points in FACT-B score with no subsequent observation of a <7-point decrease4.

ER+, oestrogen receptor-positive; FACT-B, functional assessment of cancer therapy - breast; HER2-, human epidermal growth factor receptor 2-negative; HR, hazard ratio; QoL, quality of life; TTD; time to deterioration

References:

  1. IBRANCE Summary of Product Characteristics
  2. Finn RS, et al. N Engl J Med. 2016;375:1925-1936.
  3. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.
  4. Rugo HS, et al. Ann Oncol. 2018;29:888–94.

PP-IBR-GBR-2209. January 2020

Safety

 

Treatment-emergent AEs of any cause reported in >10% of patients in either arm (safety population)2

Adapted from Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29.2

a All AEs regardless of suspected causal relationship to the study medication; MedDRA (v20.0) coding dictionary applied.2

b Clustered PTs (any event having a PT that is equal to those listed): anemia includes the PTs anemia, hematocrit decreased, and hemoglobin decreased; infections includes any PT under the system organ class infections and infestations; leukopenia includes leukopenia and white blood cell count decreased; neutropenia includes neutropenia and neutrophil count decreased; rash includes dermatitis, dermatitis acneiform, rash, rash erythematous, rash maculopapular, rash popular, rash pruritic, and toxic skin eruption; stomatitis includes aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, and stomatitis; thrombocytopenia includes platelet count decreased and thrombocytopenia.2

c In the palbociclib-letrozole arm, grade 3 and 4 febrile neutropenia were reported in 7 (1.6%) and 1 (0.2%) patients, respectively, at the time of the primary analysis (data cutoff date February 26, 2016) and in 7 (1.6%) and 2 (0.5%) patients after the additional 15 months of follow-up (data cutoff date May 31, 2017). The later data cutoff date included an additional 1 (0.2%) patient who developed grade 4 febrile neutropenia with a very slight fever (38.2 ºC) 1 week after the study drug was permanently discontinued. Because the onset of grade 3 or 4 febrile neutropenia takes a median 28 days to emerge after palbociclib is stopped and residual neutropenia is not uncommon for chemotherapy (nab-paclitaxel was the subsequent line of treatment) 7 days after its discontinuation, the chemotherapy appears to contribute to this SAE.2

d Grade 5 AEs in the palbociclib-letrozole arm were disease progression (n=3), infection (pneumonia) and respiratory failure, pulmonary embolism, acute myocardial infarction, breast cancer, breast cancer metastatic, cardiogenic shock, cardiopulmonary failure, cardiovascular insufficiency and death (all n=1): note, 1 patient had grade 5 pneumonia (infection) and grade 5 respiratory failure; grade 5 AEs in the placebo-letrozole arm were infections (n=3), pulmonary embolism, and cardiac arrest (both n=1); note, 1 patient had grade 5 pneumonia (infection) and grade 5 respiratory failure; grade 5 AEs in the placebo-letrozole arm were infections (n=3), pulmonary embolism, and cardiac arrest (both n=1); note: grade 5 pulmonary embolism and grade 5 lower respiratory tract infection were reported in 1 patient.2

AE, adverse event; AI, aromatase inhibitor; ALT, alanine aminotransferase; AST, aspartate transaminase; ER+, oestrogen receptor-positive; HER2-, human epidermal growth factor receptor 2-negative; PT, preferred term; SAE, serious adverse event.

For full safety information please consult the summary of product characteristics.

References:

  1. IBRANCE® Summary of Product Characteristics.
  2. Rugo HS, et al. Breast Cancer Res Treat. 2019;174:719–29
  3. Finn RS, et al. N Engl J Med. 2016;375:1925–36

PP-IBR-GBR-2209. January 2020