ASCO 

Publishes Rapid Guideline Update

Feedback
on PARP Inhibitors in Ovarian Cancer
By Brandon May 


November 25, 2022

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An ASCO guideline rapid update is revising guidance for the use of poly (ADP-ribose) polymerase
(PARP) inhibitor therapy for the management of ovarian cancer to include updated considerations for
the use of several di몭erent PARP inhibitor therapies based on recent phase III clinical trial data.1 The
new update revises recommendations from prior guidance published in 2020.2

There have been several clinical research advancements since the initial ASCO
guideline on PARP inhibitor use in ovarian cancer, thus necessitating the rapid
update, explained guideline Expert Panel Co-Chair Elise C. Kohn, MD, of the
National Cancer Institute. Recent randomized studies have con몭rmed the value
of PARP inhibitors as maintenance therapy for women with germline or
deleterious somatic mutations in BRCA1 or BRCA2.3

Elise C. Kohn, MD “Data show that there are still statistically and clinically signi몭cant bene몭ts for
patients with the homologous recombination biomarker, or in patients with
neither, although the bene몭t is less in the latter group,” she said.

Data on Second-Line Niraparib

The rapid update reports on recent data demonstrating detrimental survival outcomes with the use of
niraparib as second-line maintenance therapy and in the treatment of germline or somatic BRCA-
mutated cases. “The data warranted a reduction in the overall enthusiasm for niraparib from ‘should
be used’ to ‘may be used,’ for maintenance,” Dr. Kohn said, adding that a 몭nal recommendation
awaits peer review and publication of the entire overall survival data.

The guideline suggests that the decision to use second-line maintenance therapy with niraparib in
patients without germline or a somatic BRCA mutation should weigh the potential progression-free
survival bene몭t against the possible overall survival decrement.

Recent Regulatory Action for PARP Inhibitors in Third-Line Treatment

The worse overall survival with rucaparib in the phase III ARIEL4 trial4 recently caused the U.S. Food
and Drug Administration (FDA) to withdraw licensing approval for the use of the agent in the
treatment of third-line germline or somatic BRCA-mutated ovarian cancer,5 Dr. Kohn explained. “The
situation was made public in May, and the withdrawal was approved in June 2022,” she said. “Thus,
our guidelines needed to change to remove the recommendation.”

3
 3 added that recent clinical trial data showed that treatment with olaparib in patients with
Dr. Kohn
germline
S HA RE Sor somatic BRCA-mutated ovarian cancer was associated with a reduced overall survival

compared with chemotherapy.6 Given these 몭ndings, the license for olaparib was withdrawn in
August 2022.1

Similarly, in September 2022, a voluntary withdrawal of niraparib was announced for the treatment of
adults with advanced platinum-sensitive epithelial ovarian cancer who have received three or more
chemotherapy regimens and whose cancer is associated with homologous recombination de몭ciency–
positive status.7 In their rapid update, the guideline co-chairs wrote that the FDA label revision for
niraparib remains pending at the time of publication.

“This came out just before 몭nal approval of the [guideline] update and was included as a cautionary
note,” Dr. Kohn said. “Niraparib remains available for this indication, but caution was included in the
rapid update, as the [overall survival] data for the use of this agent has not yet been reported.”

The guideline now indicates that PARP inhibitor monotherapy is no longer licensed or recommended
for the treatment of recurrent platinum-sensitive epithelial ovarian cancer. As such, the guideline
committee wrote that the use of these agents in this setting “should weigh potential bene몭t with
harm in select populations,” such as those with a BRCA mutation, no prior PARP inhibitor use,
platinum-sensitive disease, and advanced lines of therapy.

Furthermore, given that the most recent regulatory changes for PARP inhibitors in ovarian cancer are
predominantly “based on secondary objective outcomes that have not yet been reported publicly,” the
new rapid recommendation update “suggests treatment with [PARP inhibitors] should be based on
individualized patient and provider assessment of risks, bene몭ts, preferences, and emerging data.” 

REFERENCES

1. Tew WP, Lacchetti C, Kohn EC: Poly (ADP-ribose) polymerase inhibitors in the management of
ovarian cancer: ASCO Guideline rapid recommendation update. J Clin Oncol. September 23, 2022 (early
release online).

2. Tew WP, Lacchetti C, Ellis A, et al: PARP inhibitors in the management of ovarian cancer: ASCO
Guideline. J Clin Oncol 38:3468-3493, 2020.

3. Tattersall A, Ryan N, Wiggans AJ, et al: Poly (ADP-ribose) polymerase (PARP) inhibitors for the
treatment of ovarian cancer. Cochrane Database Syst Rev 2:CD007929, 2022.

4. Kristeleit R, Lisyanskaya A, Fedenko A, et al: Rucaparib versus standard-of-care chemotherapy in

patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): An
international, open-label, randomised, phase 3 trial. Lancet Oncol 23:465-478, 2022.

5. Clovis Oncology: Dear health care provider letter, June 2022. Available at
https://clovisoncology.com/pdfs/US_DHCPL_몭nal_signed.pdf. Accessed November 7, 2022.

6. Penson RT, Valencia RV, Colombo N, et al: Final overall survival results from SOLO3: Phase III trial
assessing olaparib monotherapy versus non-platinum chemotherapy in heavily pre-treated patients
with germline BRCA1- and/or BRCA2-mutated platinum-sensitive relapsed ovarian cancer. 2022 SGO
Annual Meeting on Women’s Cancer. Abstract 25. Presented March 18, 2022.

7. GlaxoSmithKline: Dear health care provider letter, May 2022. Available at

https://www.zejulahcp.com/content/dam/cf-pharma/hcp-zejulahcp-
v2/en_US/pdf/ZEJULA%20(niraparib)%20Dear%20HCP%20Letter.pdf. Accessed November 7, 2022.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News,
October 6, 2022. All rights reserved.

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