A Critical Step: What Nurses Need to Know About HRD Testing for Advanced Ovarian Cancer

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As integral members of the care team, it’s imperative that nurses understand the role of tumor testing for women with advanced ovarian cancer. Approximately 50% of patients with advanced ovarian cancer have tumors that are positive for homologous recombination deficiency* or HRD. Timely tumor testing, such as HRD testing, can provide helpful information to the care team to support personalized treatment decisions.1

“When we first meet patients who have a new diagnosis of advanced ovarian cancer, one of the first things we do is refer the individual to our genetic counselor for genetic and biomarker testing. With the referral, we take the time to explain to the patient why this is an important step in the diagnostic process,” says Courtney Arn, APRN-CNP of The Ohio State University Comprehensive Cancer Center – James. “It's essential for patients to understand their genetic and biomarker mutations, as this information guides treatment plans and helps providers personalize care. Through testing, they can also find out if their family is at risk, which may drive hesitant patients to get tested.”

HRD testing early after diagnosis can help determine whether a PARP inhibitor, like LYNPARZA® (olaparib) taken in combination with bevacizumab, may be a first-line maintenance treatment option for patients with advanced ovarian cancer that have tested positive for HRD and have responded to platinum-based chemotherapy.2,3

*Select patients for this indication based on an FDA-approved companion diagnostic.

PARP=poly (ADP-ribose) polymerase

People with HRD-positive tumors may benefit from PARP inhibition1

The introduction of PARP inhibitors changed the treatment landscape over the past decade for people diagnosed with advanced or recurrent ovarian cancer. PARP inhibitors have been particularly impactful as a maintenance treatment, where the primary aim is to delay disease progression and recurrence.4-6

“When I started as an oncology nurse 10 years ago, an ovarian cancer diagnosis was a very grave discussion, but now, it’s more optimistic,” said Arn. “With maintenance therapy, if an individual is HRD positive using a PARP inhibitor, we are seeing much longer intervals before their cancer comes back, if it comes back. We’ve seen improvements in progression-free survival.”

Conversations about HRD testing with patients should start immediately after an advanced ovarian cancer diagnosis.4,7 Completing this step is critical, even if a patient has already had a biomarker test. Why? Because even without a breast cancer gene mutation (BRCAm), you can still test positive for HRD.7,8

According to Arn, “It’s important to have conversations very early on with your patients about HRD testing and the possibility of maintenance therapy. Once they finish their six cycles of chemotherapy, they think they are done. It’s crucial to have that discussion early on that ‘we think adding maintenance therapy after finishing the chemotherapy will have a positive impact on your progression-free survival.’ This way patients are prepared for it.”

Considering LYNPARZA for first-line maintenance

For women with HRD-positive advanced ovarian cancer, LYNPARZA, in combination with bevacizumab, may be an appropriate maintenance treatment option. HRD-positive status is defined by deleterious or suspected deleterious BRCAm and/or genomic instability.3

PAOLA-1

PAOLA-1 is the first Phase III trial to investigate olaparib, a PARP inhibitor, in combination regimen against an active and established maintenance therapy. PAOLA-1 evaluated the efficacy and safety of LYNPARZA in combination with bevacizumab versus placebo/bevacizumab for the maintenance treatment of advanced high-grade epithelial ovarian cancer, fallopian tube or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab.3,9-13

Patients enrolled in the intent-to-treat population were stratified by tumor BRCAm status and first-line treatment outcome. While HRD status was not a stratification factor–enrolled patients were retrospectively tested–the FDA approval was based on a prespecified exploratory subgroup analysis of patients with HRD-positive tumors (n=387), which was not controlled for Type 1 error.3,14,15

In women with HRD-positive* advanced ovarian cancer following response to first-line platinum-based chemotherapy with bevacizumab, LYNPARZA plus bevacizumab demonstrated a clinically significant median progression-free survival benefit of 3.1 years (37.2 months) vs ~1.5 years (17.7 months) with bevacizumab plus placebo (hazard ratio for disease progression or death, 0.33; 95% CI, 0.25 to 0.45). In a five-year follow-up, LYNPARZA plus bevacizumab prolonged overall survival with 65.5% of HRD-positive patients surviving five years vs 48.4% treated with bevacizumab plus placebo (HR 0.62; 95% CI, 0.45-0.85). Overall survival was used as a secondary endpoint.13,15

Updated results from the landmark PAOLA-1 trial showed that at five-year follow-up, LYNPARZA meaningfully extended the overall survival for HRD-positive patients and is the only PARP inhibitor to achieve this milestone (5-year OS rates, 65.5% versus 48.4%; median 75.2 versus 57.3 months; HR 0.62; 95% CI, 0.45-0.85).3, 9-12,15

PAOLA-1 five-year data are from a post hoc analysis of a prespecified exploratory subgroup that is based on Kaplan-Meier estimates and are descriptive only. The trial was not designed to assess a statistical difference between treatment groups at these time points.13,14,16

Adverse Reactions (ARs) were reported in more than 10% of women on LYNPARZA in combination with bevacizumab and more than 5% frequency versus bevacizumab plus placebo. With the most common ARs in the primary analysis being fatigue (including asthenia) (53%), nausea (53%), anemia (41%), lymphopenia (24%), vomiting (22%), diarrhea (18%), neutropenia
(18%), UTI (15%), headache (14%), and leukopenia (18%).3 Please see additional Important Safety Information below.

UTI=urinary tract infection


Testing for HRD supports informed, personalized treatment decisions

“Discussing how knowing your HRD status can guide the best treatment options is often what motivates patients to get tested,” explains Arn.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients with various BRCAm, gBRCAm, HRR gene-mutated or HRD- positive cancers who received LYNPARZA as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm.

In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.

Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).

In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:

  • a deleterious or suspected deleterious BRCA mutation, and/or
  • genomic instability

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance BRCA-mutated Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

You may report side effects related to AstraZeneca products.

To learn more about HRD testing and the clinical data supporting the use of LYNPARZA as a first-line maintenance treatment for women with advanced ovarian cancer, visit https://www.lynparzahcp.com/ovarian-cancer/home.html.

Courtney Arn has been compensated by AstraZeneca for her participation in this program.

References:

1. Medical News Today. What to know about HRD testing for ovarian cancer. Accessed September 2024. https://www.medicalnewstoday.com/articles/hrd-positive-ovarian- cancer.
2. Goh JCH, Gourley C, Tan DSP, et al. Optimizing treatment selection and sequencing decisions for first-line maintenance therapy of newly diagnosed advanced ovarian cancer. Gynecol Oncol Rep. 2022;42:101028.
3. LYNPARZA® (olaparib) [prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023.
4. O'Malley DM, Krivak TC, Kabil N, Munley J, Moore KN. PARP Inhibitors in Ovarian Cancer: A Review. Target Oncol. 2023;18(4):471-503.
5. Wang H, Wu M, Liu H, et al. Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta- Analysis. Front Oncol. 2021;11:785102.
6. National Cancer Institute. PARP Inhibitors Show Promise as Initial Treatment for Ovarian Cancer. Cancer Currents Blog. Accessed October 2024. https://www.cancer.gov/news- events/cancer-currents-blog/2019/parp-inhibitors-ovarian-cancer-initial-treatment.
7. Heitz F, Ataseven B, Staniczok C, et al. Implementing HRD Testing in Routine Clinical Practice on Patients with Primary High-Grade Advanced Ovarian Cancer. Cancers (Basel). 2023;15(3):818.
8. Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 2015;5(11):1137-1154.
9. Zejula® (niraparib) [prescribing information]. Waltham, MA: TESARO, Inc.; 2024.
10. Rubraca® (rucaparib) [prescribing information]. Boulder, CO: Clovis Oncology, Inc.; 2024.
11. Akeega® (niraparib and abiraterone acetate) [prescribing information]. New Brunswick, NJ: Johnson & Johnson, INC.; 2023.
12. Talzenna® (talazoparib) [prescribing information]. New York, NY: Pfizer, INC.; 2023.
13. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381(25):2416-2428.
14. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381(25):2416-2428.
15. Ray-Coquard I, Leary A, Pignata S, et al; PAOLA-1/ENGOT-ov25 investigators. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023;34(8):681-692.
16. Lorusso D, Mouret-Reynier MA, Harter P, et al. Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA- 1/ENGOT-ov25 trial. Int J Gynecol Cancer. 2024;34(4):550-558.

LYNPARZA is a registered trademark of the AstraZeneca group of companies.

US-93570 Last Updated 11/24