ARIEL3 Trial Design

ARIEL3 is the Largest Pivotal Phase 3 Trial of a PARP Inhibitor as Maintenance Treatment for Recurrent Ovarian Cancer1-4

Continue until disease progression or unacceptable toxicity1

Randomized patients evaluated per a step-down analysis of 3 nested cohorts.b,1,2

More BRCAwt patients were enrolled in ARIEL3 than any other registrational trial for an approved PARP inhibitor in the maintenance setting1-4

Flow chart of Rubraca trial design results in patients enrolled and randomizedFlow chart of Rubraca trial design results in patients enrolled and randomized

ARIEL3 Enrolled a Broad, Clinically Relevant Patient Population Including Those with a Poor Prognosis and Difficult-to-Treat Disease, Regardless of Biomarker Status

Study patients reflected a clinically relevant population1,2

Disease characteristicsc

Pie chart of BRCA wild-type disease characteristics in Rubraca patients

with residual disease

  • 37% had measurable disease (18% with bulky disease)
  • 28% had non-measurable disease (investigator-assessed)
Pie chart of BRCA wild-type disease characteristics in Rubraca patients

were BRCAwt

  • 28% (n=158) were BRCAwt, HRd
  • 29% (n=161) were BRCAwt, HRp
  • 8% (n=49) were LOH indeterminant

Treatment history

  • 66% had a PR and 34% had a CR to the last platinum-based chemotherapy
  • 64% of patients who received 2 prior lines of chemotherapy achieved a PR
  • 22% of patients had received prior bevacizumab

Patient characteristics

  • Median age for patients was 61 years (range 36-85)
  • 74% had a 0 and 26% had a 1 ECOG performance status
  • 80% of patients were white
  • Baseline characteristics were well balanced between treatment arms

HRd and HRp Efficacy

Rubraca significantly extended PFS across both HRd and HRp populations1,2,5,6

SEE THE DATA
  • aEvaluated according to RECIST v1.1.
  • b1) BRCAmut+ patients, 2) HRd patients, and 3) all randomized patients.
  • cPooled for all randomized patients (N=564)
  • BID, twice a day; BRCA, breast cancer susceptibility gene; BRCAmut+, BRCA-mutation positive, which includes mutations in the BRCA1 and/or BRCA2 gene; BRCAwt, BRCA wild-type; CR, complete response; ECOG, Eastern Cooperative Oncology Group; HR, homologous recombination; HRd, HR-deficient; HRp, HR-proficient (HRd-); LOH, loss of heterozygosity; PARP, poly (ADP-ribose) polymerase; PFS, progression-free survival; PR, partial response.

INDICATION

Rubraca is indicated 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.

SELECT IMPORTANT SAFETY INFORMATION

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 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 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 for cytogenetics. 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%).

Co-administration of rucaparib 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.

Please see full Prescribing Information for additional Important Safety Information.

Reference: 1. Rubraca. Prescribing information. Clovis Oncology; 2022. 2. Coleman RL, Oza AM, Lorusso D, et al; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949-1961.
3. LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022. 4. Zejula® (niraparib) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2021. 5. Coleman RL, Oza AM, Lorusso D, et al; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949-1961. Online supplementary appendix.

INDICATION

Rubraca is indicated 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.

SELECT IMPORTANT SAFETY INFORMATION

Read full ISI

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 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 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 for cytogenetics. 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%).

Co-administration of rucaparib 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.

Please see full Prescribing Information for additional Important Safety Information.

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