The Nurse View: Clinical Considerations in the Management of - PowerPoint Presentation

Slide1

The Nurse View: Clinical Considerations in the Management of BRCA-Mutated Advanced Ovarian Cancer

Moderator

Chrisann A. Winslow, RN, MSN, AOCNClinical Nurse SpecialistWashington UniversitySt. Louis, MissouriSlide2

PanelistsKimberly Halla, MSN, FNP-C

Nurse PractitionerDivision of Gynecology OncologyArizona Oncology

Phoenix, ArizonaKimberly Camp, RN, MSN, ANP-BC, OCNGynecology Oncology Nurse PractitionerDivision of Gynecology/Oncology

Duke

Women's Cancer Center

Raleigh,

North CarolinaSlide3

This program will include a discussion of off-label treatment and investigational agents not approved by the FDA for use in the United States, and data that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal.Slide4

a. NCCN website. Genetic/familial high-risk assessment: breast and ovarian. V2.2017.

Genetic Testing in Ovarian CancerAll patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer should be referred to a genetic counselor

Currently BRCA1 and BRCA2, at minimum, should be tested in all ovarian cancersSlide5

Germline vs Somatic Mutations

Germline mutations are

inherited and found in all cells; somatic mutations are

not inherited and are found

within the

tumor.

Germline mutation

Half of gametes carry mutation

Somatic mutation

Mutation only in affected area

Embryo

Parental gametes

Organism

Offspring gametes

None of gametes carry mutation

Embryo

Parental gametes

Entire organism carries mutation

Organism

Offspring gametes

©Medscape, LLC

©Medscape, LLCSlide6

*Including LCOH/fallopian tube/primary peritoneal cancer.NCCN website. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. v3.2017.

BRCA

Status Influences Later Lines of Treatment in Advanced OC

Primary systemic therapy regimens for epithelial

ovarian cancer

* (regardless of mutation

BRCA

mutation status)

Paclitaxel/cisplatin (IP/IV)

Paclitaxel/carboplatin (± bevacizumab)

Dose-dense paclitaxel/carboplatin

Docetaxel/carboplatin

Carboplatin + pegylated liposomal doxorubicin

BRCA

mutation status does not affect the initial

treatment.

Upon recurrence, targeted therapy options vary depending on

BRCA

mutation status.Slide7

*As indicated by an FDA-approved test. a. Lynparza®

PI 2017; b. Rubraca® PI 2016; c. Zejula® PI 2017; d.

Myriad Genetics Laboratories, Inc. website ; e. Foundation Medicine website. PARP InhibitorsOverview

Companion diagnostics are required

Olaparib has

a companion

diagnostic

that detects germline

BRCA1

and

BRCA2

mutations in blood

[d]

Rucaparib has

a companion

diagnostic

testing the tumor to detect somatic and germline

BRCA1 and BRCA2 mutations via next generation sequencing[e]

.

Agent

Target

Initial FDA

approval

FDA Indication(s)

Olaparib

[a]

PARP 1/2/3

12/19/2014Maintenance treatment in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with CR or PR to platinum-based chemotherapyTreatment of deleterious germline BRCA-mutated* advanced OC, ≥3 prior treatments or as maintenance treatment Rucaparib[b]

PARP 1/2/312/19/2016Deleterious BRCA-mutated* (germline or somatic)

advanced OC, ≥2 prior treatments Niraparib[c]PARP 1/2

3/

27/

2017

Maintenance treatment for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with CR or PR to platinum-based chemotherapySlide8

Case Study: Julie

52-year-old woman

Diagnosed 3 years ago with BRCA2-positive stage IIIC high-grade ovarian adenocarcinoma CR to initial therapy w/dose-dense paclitaxel and carboplatin after optimal debulking1 year later, relapsed

Gemcitabine/carboplatin induced a CR

The following year, scan revealed multiple omental nodules

CA125 = 340 U/mL

S

tarted

olaparib 300 mg BIDSlide9

Lynparza®PI 2017.

Most Common Olaparib-Associated AEs

Julie developed the following AEs:Grade 2 to 3 fatigueGrade 2 nauseaVomitingWeakness

Abdominal pain

Most Common AEs

(in

≥3

0% of patients

)

Patients with

≥3 Lines of Prior Chemotherapy

Receiving Olaparib (N=223)

Grade

1 to 4

Grade 3 to 4

Fatigue/asthenia

66

8

Nausea

64

3

Vomiting

43

4

Anemia

34

18Diarrhea311Slide10

Moore KN, et al. The Oncologist. 2016;21:1-10; Lynparza ® PI 2017; Rubraca ®

PI 2017; Zejula ® PI 2017.

Managing GI Toxicity With PARP InhibitorsGI toxicity and fatigue are common with all PARP inhibitors

Intervention

Description

Pharmacologic

treatments

Ondansetron for nausea (take 30 min before

olaparib)

Loperamide

for diarrhea

Atropine/diphenoxylate for diarrhea

Proton pump inhibitor

Dose modifications

May be used to manage significant diarrhea

Dietary/lifestyle

Eat smaller, more frequent meals;

avoid certain

foods, beverages; increasing fluid intake; bland diet (ie, BRAT); soluble fiber intakeSlide11

Importance of Patient Education

When starting a PARP inhibitor, patient education is keyPlan communication with your patients

Explain AE grading Discuss management optionsWhen to take anti-nausea medicationsInstruct how/when to communicate with healthcare teamEmphasize to patients not to discontinue medication on their ownSlide12

Case Study: Phyllis

66-year-old woman

BRCA1-mutated recurrent OC with brain metastasesInitial treatmentNeoadjuvant carboplatin/paclitaxel, interval optimal debulking, and adjuvant carboplatin/paclitaxel x 3 cycles1 year later, scan revealed cerebellar, parietal metastases

Craniotomy followed by stereotactic radiation

Recurrence detected 8 months later

Pegylated liposomal doxorubicin x 5 cycles

CT scan showed disease progression

Started rucaparib 600 mg BIDSlide13

Case Study: Phyllis (cont)

Grade 1 LFT elevation noted at end of cycle 1

Rucaparib dose was reduced to 500 mg2 weeks later, developed abscess in back of throat and pancytopeniaAdmitted to community hospital and intubatedSlide14

Rubraca® PI 2017. Safety Profile of Rucaparib

Nonhematologic Laboratory AEs

AST/ALT elevation can also occur with niraparibEducate patients about potential AEsMonitor regularly (more than monthly at beginning)Patients may require hydration

AE

All

Patients with OC Receiving Rucaparib (N=377)

Grade 1 to 4

Grade 3 to 4

Elevated creatinine

92

1

Elevated ALT

74

13

Elevated AST

73

5

Elevated cholesterol

40

2Slide15

AE

All

Patients with OC Receiving Rucaparib (N=377)

Any Grade

Grade 3 to 4

Decreased hemoglobin

67

23

Decreased lymphocytes

45

7

Decreased platelets

39

6

Decreased ANC

35

10

Rubraca® PI 2017.

Safety Profile of Rucaparib

Hematologic Laboratory AEs

Educate patients about potential AEs and the importance of compliance

Start with frequent monitoring and adjust as appropriateSlide16

Case Study: Helen

48-year-old woman

Presented with fallopian tube cancer, BRCA1+Carboplatin/paclitaxel induced a CR6 months later, local recurrence detectedRadiation and cisplatin followed by systemic carboplatin/paclitaxel1 year later liver metastases detected

Cisplatin/gemcitabine and bevacizumab

After 22 cycles, multiple lung nodules detected

Topotecan/bevacizumab induced a PR

Switched to niraparib 300 mg QDSlide17

Case Study: Helen (cont)

After 3 weeks

on niraparib, patient developed anemiaHb 6.7 g/dLSymptomatic w/SOBPatient received 2U PRBC; niraparib dose maintained3

weeks

later, anemia recurred

Hb 6.8 g/dL

Patient received additional 2U PRBC

Niraparib

dose was reduced

She remains on

niraparib

at lower doseSlide18

Zejula® PI 2017. Safety Profile of Niraparib

Hematologic Toxicity

Anemia can occur with all 3 FDA-approved PARP inhibitorsThrombocytopenia has also been noted with rucaparib in approximately 20% of patients; less common with olaparibEducate patients

about signs/symptoms of anemia

SOB

Vision changes

Dizziness

Headache

Change in

appetite

AE

Niraparib (n=367)

Placebo (n=179)

Grade

1 to 4

Grade 3 to 4

Grade

1 to 4

Grade 3 to 4

Thrombocytopenia

61

29

5

0.6

Anemia

50

25

7

0

Neutropenia

30

20

6

2

Leukopenia

17

5

8

0Slide19

a. Lynparza® PI 2017; b. Rubraca® PI 2017; c. Zejula ® PI 2017.

PARP Inhibitors

Safety Overview

Agent

Warnings/Precautions

Most

Common

Adverse Reactions

Most Common

Lab Abnormalities

Olaparib

[a]

MDS/AML (<1.5%), pneumonitis, embryo-fetal toxicity

(≥20%):

anemia, n

ausea, fatigue (including asthenia), vomiting, nasopharyngitis/URTI/ influenza,

diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, stomatitis

(≥25%):

d

ecrease in: hemoglobin, lymphocytes, leukocytes, ANC, platelets

Increase

in: MCV, serum creatinine

Rucaparib

[b]

MDS/AML,

embryo-fetal toxicity

(≥ 20%):

nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, dyspnea(≥35%): increase in: creatinine, ALT, AST, cholesterolDecrease in: hemoglobin, lymphocytes, platelets, ANC

Niraparib[c]MDS/AML, bone marrow suppression, cardiovascular effects, embryo-fetal toxicity(≥10%): thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, UTI, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertensionSlide20

Other Considerations With PARP InhibitorsDiscuss with patient that even though this is an oral agent, there will be AEs

Importance of compliance; possible challengesMaintain regular follow-up and communicationEncourage use of tools (calendar, medication box, reminders) to help patients manage therapySlide21

Key Takeaways

Thorough assessments are valuable for identifying and managing AEsPatients may not be forthcoming in reporting AEs

Monitor lab values including CBC, CMPAlthough oral agents are taken at home, they are active medications that require close surveillanceEducate patients about what to look for; encourage communication as issues ariseProvide patients with tools (reminders, calendars) to improve adherence and communicationSlide22

Please click Next below to see how your knowledge improved. The

CE posttest will follow. Please also take a moment to complete the program evaluation.

Thank you for participating in this activity.