Palbociclib in Combination With Fulvestrant or Letrozole in Patients With ER+, HER2- Advanced Breast Cancer

Conditions

Metastatic Breast Cancer

Keywords

metastatic breast cancer, Endocrine receptors positive, HER-2 negative

Brief summary

This is an international, randomized, open-label, controlled, multicenter phase II clinical trial to investigate and compare the safety and efficacy of palbociclib combined with fulvestrant or letrozole in women with ER+, HER2- locally advanced or metastatic breast cancer.

Detailed description

Patients will be stratified by site of disease (visceral vs. non-visceral) and by onset of metastatic disease diagnose (patients metastatic de novo versus non de novo).

Fara Brasó‐Maristany, Javier Cortés, José Manuel Pérez-García, Rosario Vega-León, Laia Paré et al. (24 authors)

Cancer Research2024-05-021 citations

10.1158/1538-7445.sabcs23-po2-15-06

Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial

Serena Di Cosimo, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel Gil‐Gil et al. (23 authors)

The Oncologist2022-10-1419 citations

10.1093/oncolo/oyac205

Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor–Positive, <i>ERBB2</i>-Negative Advanced Breast Cancer

Antonio Llombart‐Cussac, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel Gil‐Gil et al. (54 authors)

JAMA Oncology2021-10-1099 citations

10.1001/jamaoncol.2021.4301

PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[-] metastatic breast cancer.

Antonio Llombart‐Cussac, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel Gil‐Gil et al. (20 authors)

Journal of Clinical Oncology2020-05-2046 citations

10.1200/jco.2020.38.15_suppl.1007

Abstract P4-10-17: Baseline and pharmacodynamic changes of circulating exosomal microRNAs predict early versus late progression to palbociclib plus endocrine therapy in patients with metastatic breast cancer. A sub-analysis of the PARSIFAL-1 trial

David Casadevall, Joan Albanell Mestres, Federico Rojo, Beatríz Bellosillo, Abel González et al. (21 authors)

Cancer Research2020-02-15

10.1158/1538-7445.sabcs19-p4-10-17

Interventions

DRUGPalbociclib

DRUGFulvestrant

DRUGLetrozole

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy 2. Confirmed diagnosis of HR+/HER2- breast cancer 3. Post-menopausal status 4. No prior chemotherapy line in the metastatic setting 5. Measurable disease defined by RECIST version 1.1, or non-measurable disease 6. Eastern Cooperative Oncology Group (ECOG) PS 0-1 7. Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures 8. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.0 Grade equal or minor than 1

Exclusion criteria

1. ER or HER2 unknown disease 2. HER2 positive disease based on local laboratory results 3. Locally advanced breast cancer candidate for a radical treatment 4. Prior (neo)adjuvant endocrine treatment with DFI ≤ 12-months from completion of treatment. 5. Patients with rapidly progressive visceral disease or visceral crisis. 6. Major surgery within 4 weeks of start of study drug 7. Patients with an active, bleeding diathesis 8. Serious concomitant systemic disorder incompatible with the study 9. Are unable to swallow tablets 10. Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent 11. Known active uncontrolled or symptomatic CNS metastases 12. Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients 13. QTc \> 480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes 14. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug

Design outcomes

Primary

Measure	Time frame	Description
1-year Progression Free Survival	One year	Percentage of patients who are alive and without evidence of tumor progression (defined using RECIST v1.1)

Secondary

Measure	Time frame	Description
Number of Participants With Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations •	Through study completion. From baseline up to 51 months.	Grade 3/4 adverse events, SAEs, deaths and discontinuations following the CTCAE v5 criteria
Time To Progression (TTP)	Through study completion. From baseline up to 51 months.	Time from randomization to disease progression
Overall Survival (OS)	Through study completion. From baseline up to 51 months.	Time from date of randomization to date of death due to any cause
Clinical Benefit Rate	Through study completion. From baseline up to 51 months.	Percentage of patients who experience a CR, PR or stable disease (for at least 24 weeks) and assessed by modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria.
Overall Response Rate	Through study completion. From baseline up to 51 months.	Proportion of patients with best overall response of confirmed complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST criteria guidelines (version 1.1)

Countries

Czechia, France, Germany, Italy, Russia, Spain, United Kingdom

Participant flow

Recruitment details

Postmenopausal women and premenopausal women receiving LHRH analogues, aged ≥ 18 years with ER+ and HER2- with laBC or mBC that had not received any therapy for the metastatic disease.

Pre-assignment details

Screening details: * Postmenopausal and premenopausal women receiving LHRH analogues, ≥ 18 years. * ECOG score ≤ 2 * Histologically confirmed ER+ and/or PgR+ and HER2- locally advanced or MBC * Not candidates for a local treatment with a radical intention * No prior therapy for metastatic disease. * Evidence of measurable or evaluable metastatic disease

Participants by arm

Arm	Count
Arm A Combination of Palbociclib and Letrozole Palbociclib Letrozole	243
Arm B Combination of Palbociclib and Fulvestrant Palbociclib Fulvestrant	243
Total	486

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Not meet selection criteria	1	0
Overall Study	Physician Decision	1	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Arm B	Arm A	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	112 Participants	101 Participants	213 Participants
Age, Categorical Between 18 and 65 years	131 Participants	142 Participants	273 Participants
Age, Continuous	64 years	62 years	63 years
Ethnicity (NIH/OMB) Hispanic or Latino	130 Participants	125 Participants	255 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	106 Participants	107 Participants	213 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants	11 Participants	18 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	1 Participants	3 Participants
Race (NIH/OMB) Black or African American	3 Participants	1 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	11 Participants	18 Participants
Race (NIH/OMB) White	231 Participants	230 Participants	461 Participants
Region of Enrollment Czechia	7 participants	7 participants	14 participants
Region of Enrollment France	36 participants	34 participants	70 participants
Region of Enrollment Germany	13 participants	11 participants	24 participants
Region of Enrollment Italy	17 participants	21 participants	38 participants
Region of Enrollment Russia	15 participants	16 participants	31 participants
Region of Enrollment Spain	130 participants	125 participants	255 participants
Region of Enrollment United Kingdom	25 participants	29 participants	54 participants
Sex: Female, Male Female	243 Participants	243 Participants	486 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 243	8 / 243
other Total, other adverse events	242 / 243	241 / 243
serious Total, serious adverse events	51 / 243	72 / 243

Outcome results

Primary

1-year Progression Free Survival

Percentage of patients who are alive and without evidence of tumor progression (defined using RECIST v1.1)

Time frame: One year

Arm	Measure	Value (NUMBER)
Arm A	1-year Progression Free Survival	79.4 percentage of participants
Arm B	1-year Progression Free Survival	77.9 percentage of participants

Secondary

Clinical Benefit Rate

Percentage of patients who experience a CR, PR or stable disease (for at least 24 weeks) and assessed by modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria.