PALMIRA
Research type
Research Study
Full title
INTERNATIONAL, MULTICENTER, RANDOMIZED, OPEN-LABEL, PHASE II CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF CONTINUATION OF PALBOCICLIB IN COMBINATION WITH SECOND-LINE ENDOCRINE THERAPY IN HORMONE RECEPTORPOSITIVE/ HER2-NEGATIVE ADVANCED BREAST CANCER PATIENTS WHO HAVE ACHIEVED CLINICAL BENEFIT DURING FIRST-LINE PALBOCICLIB-BASED TREATMENT
IRAS ID
259240
Contact name
Iain Roderick James MacPherson
Contact email
Sponsor organisation
Medica Scientia Innovation Research (MedSIR)
Eudract number
2017-002781-48
Duration of Study in the UK
3 years, 4 months, 31 days
Research summary
This is a multi-centre, randomized, open-label, phase II trial.
The trial aims to confirm if palbociclib rechallenge combined with second-line endocrine therapy upon progression on first-line combination of palbociclib plus endocrine therapy can improve progression free survival over endocrine therapy alone in HR-positive/HER2-negative advanced breast cancer patients.
After knowing the results of previous trials, there is now enough evidence to consider that CDK4/6 inhibitors (like palbociclib) in combination with endocrine therapy will be the standard of care for the first-line treatment of post-menopausal women with HR positive/ HER2-negative metastatic breast cancer in the coming years.
In addition, data from a previous trial has also confirmed a significant benefit with the addition of palbociclib to standard second-line hormone therapy in palbociclib-naïve patients.
To date, we have no data on the efficacy of the rechallenge of palbociclib after having documented disease progression on previous first-line palbociclib-containing endocrine regimen in patients who have achieved prior clinical benefit with this treatment.
Therefore, it seems imperative to explore the efficacy of the combination of palbociclib and endocrine therapy (letrozole or fulvestrant) as a second-line treatment in patients who had previously received another endocrine therapy in combination with palbociclib and had achieved clinical benefit during first-line
palbociclib-based treatment with subsequent disease progression.Summary of Results
Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer are first treated with a combination of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and endocrine therapy, where CDK4/6 inhibitors work by stopping cancer cells growth and endocrine therapy blocks hormones that stimulate cancer cell growth. However, the best treatment for patients who progress on a CDK4/6 inhibitors therapy remains unknown. Despite ongoing research to determine the optimal treatment strategy for these patients, the best approach remains unclear. Some studies suggest that cancer may become resistant to endocrine therapy more easily than to CDK4/6 inhibitors. To address this gap in knowledge, the PALMIRA trial has been designed to explore if keeping patients on palbociclib (a CDK4/6 inhibitor) but giving a different type of endocrine therapy (with the drugs letrozole or fulvestrant) can improve the effectiveness of second-line treatment in patients with HR[+]/HER2[-] advanced breast cancer.
PALMIRA was an international, randomized, open-label phase II trial across 44 hospitals in 6 countries, that enrolled 198 patients with HR+/HER2- advanced breast cancer who had experienced disease progression after initially responding to treatment with the immediately prior regimen of palbociclib plus endocrine therapy. Patients were randomly allocated to receive either palbociclib plus endocrine therapy or endocrine therapy alone. The choice of endocrine therapy administered during this trial was switched based on the previously administered agent: patients previously treated with fulvestrant changed to letrozole, whereas patients previously treated with letrozole, anastrozole or exemestane were switched to fulvestrant. The primary objective of the study was to determine the amount of time from the start of the treatment until the disease got worse again, also called progression-free survival (PFS).
The results show that, after a median follow-up of 13.2 months, there was no significant difference in the length of time that patients' conditions got worse between the two groups. Median PFS was 4.9 months in the palbociclib plus endocrine therapy group and 3.6 months in the endocrine therapy alone group. However, differences in the median PFS and clinical benefit rates at 6 months were observed between groups, suggesting that a subset of patients may benefit from continuing palbociclib treatment. Several biomarker studies are planned to identify which patients are most likely to benefit from adding CDK4/6 inhibitor to their treatment.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
19/EE/0101
Date of REC Opinion
12 Jun 2019
REC opinion
Further Information Favourable Opinion