Findings Link Olaparib as Maintenance Drug to Reduced Disease Progression in Advanced Ovarian Cancer

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Directions in Pharmacy, June 2021, Volume 3, Issue 3
Pages: 10

Study results demonstrated consistent benefit across higher and lower-risk patients.

In women with advanced ovarian cancer, a PARP inhibitor used as maintenance therapy after primary treatment has been shown to significantly lengthen progression-free survival (PFS).

The drug, olaparib (Lynparza; AstraZeneca), is an oral targeted chemotherapy drug that stops the cancer cell’s PARP enzyme from repairing DNA damage, which makes it important in disease progression.1

An estimated 21,410 new diagnoses of ovarian cancer in the United States are projected for 2021, and about 13,770 women will die from ovarian cancer this year, according to the American Cancer Society.2

Used as maintenance therapy for 2 years after primary treatment of women with advanced ovarian cancer, olaparib has been shown to significantly lengthen 5-year PFS, according to results of the SOLO-1 study (NCT01844986).1,3

“Even years after patients completed the planned 2 years of olaparib treatment, their progression-free survival benefit endured,” lead author, William Bradley, MD, a gynecologic oncologist at Froedtert and the Medical College of Wisconsin, Milwaukee, said in a prepared statement. “That’s very good news.”1

Data from the SOLO-1 study that investigated olaparib was presented during 2021 sessions at the Hematology/ Oncology Pharmacy Association (HOPA) virtual conference and the Society of Gynecologic Oncology (SGO) Virtual Annual Meeting on Women’s Cancer.1,3,4

The objective of maintenance therapy is to slow the cancer’s growth after initial treatment, usually with platinum-based chemotherapy and surgical treatment. Olaparib was studied in patients with a mutation, or harmful alteration, of the BRCA1 and/or BRCA2 genes. The mutation is present in about one-fourth of women with ovarian cancer, according to Bradley.2

The SOLO-1 study evaluated 5 years of follow-up data from a prior study, which Bradley called “the longest follow-up for any PARP inhibitor in the setting of maintenance therapy after primary therapy” during the SGO session.1

Colleen Bohnenkamp, PharmD, BCOP, BCPS, reviewed the traditional treatment pathway during the HOPA presentation. The treatment pathway begins with neoadjuvant platinum-based chemotherapy for eligible patients, followed by surgical staging and debulking, adjuvant platinum-based chemotherapy, observation or frontline maintenance therapy, and more chemotherapy if a relapse occurs, she said. An occurrence within 6 months of chemotherapy, she noted, is considered platinum-resistant and has lower survival rates, whereas an occurrence more than 6 months after chemotherapy is platinum-sensitive.4

According to Bohnenkamp, olaparib was the first approved frontline PARP inhibitor, with its approval based on the SOLO-1 trial. Results were first
reported in 2018, with investigators finding a long PFS benefit. Notably, the secondary outcome of a second median PFS has not yet been reached. These findings suggest that olaparib does not limit patients’ ability to respond to future therapies, which Bohnenkamp said is an important consideration without an abundance of clinical data yet.4

The SOLO-1 study included 391 patients with a BRCA mutation and newly diagnosed advanced ovarian cancer who first completed platinum-based chemotherapy. Olaparib was given at random to 260 women; 131 others received a placebo for 2 years or until the cancer worsened.1,3

The data analysis found that more than twice as many women who received olaparib were alive 5 years after the beginning of the study with no progression of their cancer. More than 48% of olaparib recipients had 5-year PFS vs only 20.5% of placebo recipients, according to the study authors.1,3

Further, the researchers analyzed subgroups of patients depending on their risk of disease progression; compared with those who got placebo, olaparib recipients had better 5-year PFS regardless of their initial progression risk.1,3

“Olaparib maintenance therapy should be a standard of care for women with a BRCA mutation and advanced ovarian cancer,” Bradley said.1

The safety profile of olaparib shown in SOLO-1 was consistent with previous observations, according to the study authors.3 These results shared a consistent safety profile with the SOLO-2 trial (NCT03470805), with anemia and neutropenia noted as common adverse events (AEs).4

Potential AEs of olaparib include blood abnormalities. Bradley suggested that patients taking olaparib receive routine physical assessments and laboratory tests under an oncologist’s care.1

Pharmacists can play an important role by closely monitoring patients, including conducting follow-ups between provider visits.4

REFERENCES

  1. For advanced ovarian cancer, olaparib as maintenance drug reduces disease progression, five-year follow-up data show. News release. Society of Gynecologic Oncology. March 20, 2021. Accessed May 17, 2021. https://www.sgo.org/news/maintenance-olaparib-for-patients-with-newly-diagnosed-advanced-ovarian-cancer-and-a-brca-mutation-5-year-follow-up-from-solo1/
  2. Key statistics for ovarian cancer. American Cancer Society. Reviewed January 12, 2021. Accessed May 11, 2021. https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html
  3. Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO-1. Presented at: Society of Gynecologic Oncology 2021 Annual Meeting on Women’s Cancer; March 19-25, 2021; virtual.
  4. Bohnenkamp C. Approaches to maintenance treatment for ovarian cancer: single agent PARP inhibitor or combination? Presented at: Hematology/Oncology Pharmacy Association Virtual conference; April 14, 2021.