Quality-adjusted progression free survival (QA-PFS) and
quality-adjusted time without cancer related symptoms or toxicity
(Q-TWiST) demonstrate the benefit of Rubraca maintenance treatment over
placebo from a patient perspective
Data presented at the International Society for Pharmacoeconomics and
Outcomes (ISPOR) 2019 Annual Meeting
BOULDER, Colo.–(BUSINESS WIRE)–Clovis Oncology, Inc. (NASDAQ: CLVS) today announced data demonstrating
that patients with recurrent ovarian cancer who received Rubraca in the
Phase 3 ARIEL3 study had longer periods of quality-adjusted time without
clinically relevant symptoms as compared to patients who received
placebo, and that Rubraca maintenance treatment continued to provide
significant benefit in progression-free survival when weighted with
patients’ perceptions of their wellbeing. The presentation today at the
International Society for Pharmacoeconomics and Outcomes (ISPOR) Annual
Meeting in New Orleans highlights post-hoc evaluations of
quality-adjusted time without symptoms or toxicity (Q-TWiST) and
quality-adjusted PFS (QA-PFS) from the randomized, placebo-controlled
study of Rubraca®▼(rucaparib) for the maintenance treatment
of patients with recurrent ovarian cancer. To the company’s knowledge,
this is the first time that Q-TWiST data will be presented in the
maintenance therapy setting in recurrent ovarian cancer.
“The goal of maintenance therapy for recurrent ovarian cancer is to
delay disease progression without compromising a patient’s quality of
life,” said Robert L. Coleman, MD, professor of Department of
Gynecologic Oncology and Reproductive Medicine, The University of Texas
MD Anderson Cancer Center. “The findings from QA-PFS and Q-TWiST
analyses of ARIEL3 data demonstrate that the clinical benefits of
rucaparib as maintenance therapy were retained across all trial
populations. These results further support the positive benefit-risk
profile of rucaparib in ARIEL3, including the absence of a detrimental
effect on patient-centered outcomes across all treatment cohorts in the
study.”
During the study, patients were asked to complete EuroQol’s
five-dimension, three-level (EQ-5D-3L) questionnaire at screening, on
day 1 of each treatment cycle, at the treatment discontinuation visit,
and at the 28-day follow-up visit. QA-PFS and Q-TWiST analyses were
calculated using EQ-5D-3L data as described in the poster.
Patient-centered outcomes were examined in the intent-to-treat (ITT)
population (all randomized patients), in patients with a BRCA mutation,
and in subgroups of patients with BRCA wild-type carcinomas based on
loss of heterozygosity (LOH) status (BRCA wild type/LOH high; BRCA wild
type/LOH low; and BRCA wild type/LOH indeterminate).
Results from the study include:
-
- Mean QA-PFS was significantly longer in the Rubraca arm than placebo
arm (12.02 vs 5.74 months) for the ITT population and for patients
with a BRCA mutation (15.28 vs. 5.92 months)
- Mean QA-PFS was significantly longer in the Rubraca arm than placebo
-
- In patients with a BRCA wild-type carcinoma, mean QA-PFS was longer in
the Rubraca arm than the placebo arm regardless of LOH status
- In patients with a BRCA wild-type carcinoma, mean QA-PFS was longer in
-
- Mean Q-TWiST analysis using all grade ≥3 treatment-emergent adverse
events (TEAEs) was significantly longer in the rucaparib arm than
placebo for the ITT population (13.32 vs 6.44 months) and for patients
with a BRCA mutation (16.42 vs 6.70 months)
- Mean Q-TWiST analysis using all grade ≥3 treatment-emergent adverse
-
- In the analyses using TEAEs of interest (grade ≥2 TEAEs of nausea,
vomiting, fatigue, and asthenia), Q-TWiST was also longer in the
rucaparib arm than placebo for the ITT population (13.16 vs 6.40
months) and for patients with BRCA mutation (16.24 vs 6.68 months)
- In the analyses using TEAEs of interest (grade ≥2 TEAEs of nausea,
-
- In patients with BRCA wild-type carcinoma, longer Q-TWiST was also
observed in the Rubraca treated arm, regardless of LOH status
- In patients with BRCA wild-type carcinoma, longer Q-TWiST was also
“It is very important to evaluate patients’ perceptions of their
well-being during any type of treatment, particularly in the maintenance
therapy setting in which patients may be on therapy for an extended
period of time,” said Professor Jonathan Ledermann, M.D., Professor of
Medical Oncology, UCL Cancer Institute and UCL Hospitals, London. “These
QA-PFS and Q-TWiST data from ARIEL3 integrate the patient perspective
over the course of follow-up until progression to reflect their overall
experience over time and suggests that the toxicity which may occur with
rucaparib doesn’t outweigh its clinical benefit as maintenance treatment
for women with recurrent ovarian cancer.”
The Rubraca ISPOR poster will be available online at http://clovisoncology.com/pipeline/scientific-presentations/
as of the time it is presented at the meeting.
About Quality-Adjusted PFS (QA-PFS) and Quality-Adjusted Time Without
Symptoms or Toxicity (Q-TWiST)
-
- QA-PFS represents the duration of survival without disease
progression, adjusted for the value the patient placed on their health
status – i.e. it is a survival measure that adjusts for patient
perceptions of treatment toxicity and any associated detrimental
effects.
- QA-PFS represents the duration of survival without disease
-
- Q-TWiST results were derived by subtracting from the survival
endpoint all time in which patients experienced treatment toxicity or
disease symptoms, and then multiplying this area under the curve by a
patient-derived utility value. Q-TWiST therefore adds additional value
not available in a traditional TWiST analysis because it reflects
patients’ perceptions of the impact of toxicity on the survival
endpoint.
- Q-TWiST results were derived by subtracting from the survival
About the ARIEL3 Clinical Trial
The ARIEL3 pivotal study of rucaparib is a confirmatory randomized,
double-blind study comparing the effects of rucaparib against placebo to
evaluate whether rucaparib given as a maintenance treatment to
platinum-sensitive ovarian cancer patients can extend the period of time
for which the disease is controlled after a complete or partial response
to platinum-based chemotherapy. The study enrolled 564 patients with
high-grade epithelial ovarian, fallopian tube or primary peritoneal
cancer. To be eligible for the study, participants had to have received
at least two prior platinum-based treatment regimens, been sensitive to
the penultimate platinum regimen, and achieved a complete or partial
response to their most recent platinum-based regimen. There were no
genomic selection criteria for this study. Trial participants were
randomized 2:1 to receive 600 milligrams of rucaparib twice daily (BID)
or placebo. The study achieved its primary endpoint of improved PFS by
investigator review in each of three populations. PFS was also improved
in the rucaparib group compared with placebo by independent review, a
key secondary endpoint, in all three populations. In addition, rucaparib
improved objective response rate vs placebo among evaluable trial
participants in all three study populations.
About Rubraca (rucaparib)
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3
being developed in multiple tumor types, including ovarian and
metastatic castration-resistant prostate cancers, as monotherapy, and in
combination with other anti-cancer agents. Exploratory studies in other
tumor types are also underway.
Rubraca U.S. FDA Approved Indications
Rubraca is indicated as monotherapy for the maintenance treatment of
adult patients with recurrent epithelial ovarian, fallopian tube, or
primary peritoneal cancer who are in a complete or partial response to
platinum-based chemotherapy.
Rubraca is indicated as monotherapy for the treatment of adult patients
with deleterious BRCA mutations (germline and/or somatic) associated
epithelial ovarian, fallopian tube, or primary peritoneal cancer who
have been treated with two or more chemotherapies and selected for
therapy based on an FDA-approved companion diagnostic for Rubraca.
Select Important Safety Information
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur
uncommonly in patients treated with Rubraca and are potentially fatal
adverse reactions. In approximately 1100 treated patients, MDS/AML
occurred in 12 patients (1.1%), including those in long-term follow-up.
Of these, five occurred during treatment or during the 28-day safety
follow-up (0.5%). The duration of Rubraca treatment prior to the
diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The
cases were typical of secondary MDS/cancer therapy-related AML; in all
cases, patients had received previous platinum-containing regimens
and/or other DNA-damaging agents. Do not start Rubraca until patients
have recovered from hematological toxicity caused by previous
chemotherapy (≤ Grade 1).
Monitor complete blood counts for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or
reduce dose (see Dosage and Administration [2.2] in full Prescribing
Information) and monitor blood counts weekly until recovery. If the
levels have not recovered to Grade 1 or less after 4 weeks, or if
MDS/AML is suspected, refer the patient to a hematologist for further
investigations, including bone marrow analysis and blood sample
cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.
Based on its mechanism of action and findings from animal studies,
Rubraca can cause fetal harm when administered to a pregnant woman.
Apprise pregnant women of the potential risk to a fetus. Advise females
of reproductive potential to use effective contraception during
treatment and for 6 months following the last dose of Rubraca.
Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea
(76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash
(43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%),
constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia
(29%), nasopharyngitis/upper respiratory tract infection (29%),
stomatitis (28%), decreased appetite (23%) and neutropenia (20%).
Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were
increase in creatinine (98%), decrease in hemoglobin (88%), increase in
cholesterol (84%), increase in alanine aminotransferase (ALT) (73%),
increase in aspartate aminotransferase (AST) (61%), decrease in
platelets (44%), decrease in leukocytes (44%), decrease in neutrophils
(38%), increase in alkaline phosphatase (37%) and decrease in
lymphocytes (29%).
Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4)
were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%),
constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea
(34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).
Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%;
Grade 1–4) were increase in creatinine (92%), increase in alanine
aminotransferase (ALT) (74%), increase in aspartate aminotransferase
(AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes
(45%), increase in cholesterol (40%), decrease in platelets (39%) and
decrease in absolute neutrophil count (35%).
Co-administration of Rubraca can increase the systemic exposure of
CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the
risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A,
CYP2C9, or CYP2C19 substrates, if clinically indicated. If
co-administration with warfarin (a CYP2C9 substrate) cannot be avoided,
consider increasing frequency of international normalized ratio (INR)
monitoring. Because of the potential for serious adverse reactions in
breast-fed children from Rubraca, advise lactating women not to
breastfeed during treatment with Rubraca and for 2 weeks after the last
dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You
may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.
Click
here for full Prescribing Information and additional Important
Safety Information.
Rubraca®▼ (rucaparib) EU Authorized Use and
Important Safety Information
Rucaparib is indicated as monotherapy for the maintenance treatment of
adult patients with platinum-sensitive relapsed high-grade epithelial
ovarian, fallopian tube, or primary peritoneal cancer who are in
response (complete or partial) to platinum-based chemotherapy.
Rucaparib is indicated as monotherapy treatment of adult patients with
platinum sensitive, relapsed or progressive, BRCA mutated (germline
and/or somatic), high-grade epithelial ovarian, fallopian tube, or
primary peritoneal cancer, who have been treated with two or more prior
lines of platinum-based chemotherapy, and who are unable to tolerate
further platinum-based chemotherapy.
Summary warnings and precautions: Haematological toxicity:
Patients should not start Rubraca until they have recovered from
haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade
1). Complete blood count testing prior to starting treatment with
Rubraca and monthly thereafter is advised. Rubraca should be interrupted
or dose reduced and blood counts monitored weekly until recovery for the
management of low blood counts. Myelodysplastic syndrome/acute myeloid
leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be
referred to a haematologist for further investigation. If MDS/AML is
confirmed, Rubraca should be discontinued. Photosensitivity: Patients
should avoid spending time in direct sunlight as they may burn more
easily. When outdoors, patients should wear protective clothing and
sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low
grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose
reduction or interruption. Additionally, antiemetics may be considered
for treatment or prophylaxis.
Click
here to access the current Summary of Product Characteristics.
Healthcare professionals should report any suspected adverse reactions
via their national reporting systems.
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on
acquiring, developing and commercializing innovative anti-cancer agents
in the U.S., Europe and additional international markets. Clovis
Oncology targets development programs at specific subsets of cancer
populations, and simultaneously develops, with partners, for those
indications that require them, diagnostic tools intended to direct a
compound in development to the population that is most likely to benefit
from its use. Clovis Oncology is headquartered in Boulder, Colorado,
with additional office locations in the U.S. and Europe. Please visit www.clovisoncology.com
for more information.
To the extent that statements contained in this press release are not
descriptions of historical facts regarding Clovis Oncology, they are
forward-looking statements reflecting the current beliefs and
expectations of management. Such forward-looking statements
involve substantial risks and uncertainties that could cause our future
results, performance or achievements to differ significantly from that
expressed or implied by the forward-looking statements. Such risks and
uncertainties include, among others, whether future study results will
be consistent with study findings to date and whether future study
results will support continued development or regulatory
approval. Clovis Oncology does not undertake to update or revise any
forward-looking statements. A further description of risks and
uncertainties can be found in Clovis Oncology’s filings with
the Securities and Exchange Commission, including its Annual Report on
Form 10-K and its reports on Form 10-Q and Form 8-K.
Contacts
Clovis Investor Contacts:
Anna Sussman, 303-625-5022
asussman@clovisoncology.com
or
Breanna
Burkart, 303-625-5023
bburkart@clovisoncology.com
Clovis
Media Contacts: U.S.
Lisa Guiterman, 301-217-9353
clovismedia@sambrown.com
or
Christy
Curran, 615-414-8668
clovismedia@sambrown.com
Clovis
Media Contact: EU
Ann Hughes, +44 (0) 7956 700 790
Ann.Hughes@publicisresolute.com