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 different PARP inhibitor therapies based on recent phase III clinical trial data.1 The new update revises recommendations from prior guidance published in 2020.2
Elise C. Kohn, MD
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 confirmed the value of PARP inhibitors as maintenance therapy for women with germline or deleterious somatic mutations in BRCA1 or BRCA2.3
“Data show that there are still statistically and clinically significant benefits for patients with the homologous recombination biomarker, or in patients with neither, although the benefit 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 final 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 benefit 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.”
Dr. Kohn added that recent clinical trial data showed that treatment with olaparib in patients with germline or somatic BRCA-mutated ovarian cancer was associated with a reduced overall survival compared with chemotherapy.6 Given these findings, 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 deficiency–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 final 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 benefit 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, benefits, preferences, and emerging data.”
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_final_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.