- The PRIMA study, presented in a Presidential Symposium at the
2019 European Society for Medical Oncology congress and
simultaneously published in The New England Journal of
Medicine, demonstrates that niraparib treatment resulted in a
38% reduction in the risk of disease progression or death in the
overall study population when compared to placebo
- Importantly women in both the HR-deficient ('HRD positive') and
HR-proficient ('HRD negative') subgroups experienced a clinically
meaningful and statistically significant benefit
LONDON, Sept. 28, 2019 /CNW/ -- GlaxoSmithKline plc
(LSE/NYSE: GSK) today announced results from PRIMA
(ENGOT-OV26/GOG-3012), the Phase 3 randomised, double-blind,
placebo-controlled study of Zejula (niraparib) as a maintenance
therapy in women with first-line ovarian cancer following a
response to platinum-based chemotherapy. Niraparib treatment
resulted in a 38% reduction in the risk of disease progression or
death in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75;
p<0.001).
These results were driven by a clinically meaningful reduction
in risk of progression in women with:
- BRCA mutation tumours (risk reduction of 60%, HR 0.40 (95%
CI, 0.27–0.62) p<0.001).
- HR-deficient BRCA wild type tumours (risk reduction of 50%, HR
0.50 (95% CI, 0.30–0.83), p=0.006).
- HR-proficient tumours (risk reduction of 32%, HR 0.68 (95%
CI, 0.49–0.94), p=0.020).
The PRIMA study enrolled patients with a response to their
first-line treatment with platinum-based chemotherapy including
those with high risk of disease progression, a population with high
unmet need and previously under-represented in first-line ovarian
cancer studies.
Dr. Hal Barron, Chief Scientific
Officer and President R&D, GSK said: "Ovarian cancer is the
eighth most commonly occurring cancer in women worldwide and women
with this devastating disease have a five-year survival rate of
less than 50%. PRIMA is a landmark study as we believe these data
have the potential to fundamentally change how women with ovarian
cancer are treated."
In an interim analysis of overall survival (OS), niraparib also
demonstrated an encouraging trend toward improvement in OS relative
to placebo. A pre-planned interim analysis of OS numerically
favoured niraparib in the overall population (HR 0.70; 95% CI
0.44-1.11). In the HR-deficient subgroup, 91% of women on niraparib
were alive at 24 months vs. 85% for placebo (HR=0.61; 95% CI,
0.27-1.40). These data are not yet mature, and the significance is
not fully known. The OS interim analysis also showed 81% of women
receiving niraparib in the HR-proficient subgroup were alive at 24
months vs. 59% of women receiving placebo (HR=0.51; 95% CI,
0.27-0.97).
Dr. Antonio Gonzalez,
co-director, department of medical oncology, Clinica Universidad de
Navarra, and Primary Investigator for PRIMA said: "The PRIMA study
demonstrated the importance of maintenance therapy and the benefit
that niraparib provided to women with ovarian cancer. I believe
that niraparib monotherapy after surgery and platinum-based
chemotherapy could be an important new treatment option for
patients."
Niraparib is not currently approved in the first-line ovarian
cancer maintenance setting. GSK will share these data with the
relevant health authorities and is on track to file by the end of
the year.
The safety profile demonstrated in PRIMA did not differ from the
established safety profile. The most common grade 3 or higher
adverse events with niraparib included anaemia (31%),
thrombocytopenia (29%), and neutropenia (13%). Implementation of an
individualised dosing regimen based on body weight and/or platelet
count reduced the incidence of haematological treatment-emergent
adverse events. No new safety signals were identified. Validated
patient reported outcomes indicate quality of life was similar
between the niraparib and placebo treatment arms.
Niraparib is marketed in the United
States and Europe under the
trade name Zejula®.
About PRIMA
PRIMA is a double-blind, randomised Phase
3 study designed to evaluate niraparib versus placebo in first-line
Stage III or IV ovarian cancer patients. The study assessed the
efficacy of niraparib as maintenance treatment, as measured by
progression free survival. Patients with a response to first-line
platinum chemotherapy were randomised 2:1 to niraparib or placebo.
The trial was amended to include an individualised niraparib
starting dose of 200 mg once-daily in patients with baseline weight
<77kg and/or platelet count <150K/μL and 300 mg in all other patients.
About Zejula (niraparib)
Niraparib is indicated as
monotherapy for the maintenance treatment of adult patients with
platinum-sensitive relapsed high grade serous epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in response
(complete or partial) to platinum-based chemotherapy.
Niraparib is an oral, once-daily PARP inhibitor that is
currently being evaluated in three pivotal trials. GSK is building
a robust niraparib franchise by assessing activity across multiple
tumour types and by evaluating several potential combinations of
niraparib with other therapeutics. The ongoing development
programme for niraparib includes a Phase 3 trial as first-line
monotherapy maintenance treatment in patients with first-line
ovarian cancer (the PRIMA trial), a Phase 3 study as a first-line
triplet maintenance treatment in ovarian cancer (FIRST), a Phase 3
trial for the treatment of patients with germline
BRCA-mutated, metastatic breast cancer (the BRAVO trial),
and a Phase 2 study of niraparib combined with bevacizumab
maintenance treatment in advanced ovarian cancer (OVARIO).
Several combination studies are also underway, including trials
of niraparib plus pembrolizumab in metastatic, triple-negative
breast cancer and advanced, platinum-resistant ovarian cancer (the
TOPACIO trial). Janssen Biotech has licensed rights to develop and
commercialise niraparib specifically for patients with prostate
cancer worldwide, except in Japan.
Important Safety Information for
ZEJULA
Myelodysplastic Syndrome/Acute Myeloid Leukaemia
(MDS/AML), including some fatal cases, was reported in 1.4% of
patients receiving ZEJULA vs 1.1% of patients receiving placebo in
Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all
clinical studies. The duration of ZEJULA treatment in patients
prior to developing MDS/AML varied from <1 month to 2 years. All
patients had received prior chemotherapy with platinum and some had
also received other DNA damaging agents and radiotherapy.
Discontinue ZEJULA if MDS/AML is confirmed.
Haematologic adverse reactions (thrombocytopenia, anaemia and
neutropenia) have been reported in patients receiving ZEJULA. Grade
≥3 thrombocytopenia, anaemia and neutropenia were reported in 29%,
25%, and 20% of patients receiving ZEJULA, respectively.
Discontinuation due to thrombocytopenia, anaemia, and neutropenia
occurred, in 3%, 1%, and 2% of patients, respectively. Do not start
ZEJULA until patients have recovered from haematological toxicity
caused by prior chemotherapy (≤ Grade 1). Monitor complete blood
counts weekly for the first month, monthly for the next 11 months
of treatment, and periodically thereafter. If haematological
toxicities do not resolve within 28 days following interruption,
discontinue ZEJULA, and refer the patient to a haematologist for
further investigations.
Hypertension and hypertensive crisis have been reported in
patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of
patients receiving ZEJULA vs 2% of patients receiving placebo in
Trial 1, with discontinuation occurring in <1% of patients.
Monitor blood pressure and heart rate monthly for the first year
and periodically thereafter during treatment with ZEJULA. Closely
monitor patients with cardiovascular disorders, especially coronary
insufficiency, cardiac arrhythmias, and hypertension. Manage
hypertension with antihypertensive medications and adjustment of
the ZEJULA dose, if necessary.
Based on its mechanism of action, ZEJULA can cause foetal harm.
Advise females of reproductive potential of the potential risk to a
foetus and to use effective contraception during treatment and for
6 months after receiving their final dose. Because of the potential
for serious adverse reactions from ZEJULA in breastfed infants,
advise lactating women to not breastfeed during treatment with
ZEJULA and for 1 month after receiving the final dose.
In clinical studies, the most common adverse reactions (Grades
1-4) in ≥10% of patients included: thrombocytopenia (61%), anaemia
(50%), neutropenia (30%), leukopenia (17%), palpitations (10%),
nausea (74%), constipation (40%), vomiting (34%), abdominal
pain/distention (33%), mucositis/stomatitis (20%), diarrhoea (20%),
dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased
appetite (25%), urinary tract infection (13%), aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) elevation
(10%), myalgia (19%), back pain (18%), arthralgia (13%), headache
(26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety
(11%), nasopharyngitis (23%), dyspnoea (20%), cough (16%), rash
(21%) and hypertension (20%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients
included: decrease in haemoglobin (85%), decrease in platelet count
(72%), decrease in white blood cell count (66%), decrease in
absolute neutrophil count (53%), increase in AST (36%) and increase
in ALT (28%).
About Ovarian Cancer
Approximately 300,000 women are
diagnosed with ovarian cancer each year. Ovarian cancer is the
eighth most frequent cause of cancer death among women. Despite
high response rates to platinum-based chemotherapy in the
second-line advanced treatment setting, approximately 85% of
patients will experience recurrence within two years. Late-line
treatment options for patients with ovarian cancer are few, with
the proportion of patients achieving an overall response typically
less than 10% when treated with chemotherapy.
GSK in Oncology
GSK is focused on maximising patient
survival through transformational medicines. GSK's pipeline is
focused on immuno-oncology, cell therapy, cancer epigenetics and
synthetic lethality. Our goal is to achieve a sustainable flow of
new treatments based on a diversified portfolio of investigational
medicines utilising modalities such as small molecules, antibodies,
antibody drug conjugates and cells, either alone or in
combination.
About GSK
GSK is a science-led global healthcare
company with a special purpose: to help people do more, feel
better, live longer. For further information please visit
www.gsk.com.
Cautionary statement regarding forward-looking
statements
GSK cautions investors that any forward-looking
statements or projections made by GSK, including those made in this
announcement, are subject to risks and uncertainties that may cause
actual results to differ materially from those projected. Such
factors include, but are not limited to, those described under Item
3.D 'Principal risks and uncertainties' in the company's Annual
Report on Form 20-F for 2018.
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