Long-Term Maintenance Olaparib Safe and Effective for Patients With Recurrent Ovarian Cancer

Jacob Korach, MD

Long-term maintenance therapy with olaparib (Lynparza) tablets demonstrated a low rate of treatment discontinuation and tolerable safety profile in patients with platinum-sensitive recurrent ovarian cancer, according to an analysis from the phase III SOLO-2 trial.¹

The findings, which were presented at the 2018 ESMO Congress, showed that olaparib was associated with mainly low-grade adverse events (AEs) that occurred within the first year of therapy.

“The incidence of AEs was lower during the second year (>1 to <2 years) of treatment and was then further reduced in patients receiving olaparib for over 2 years,” Jacob Korach, MD, deputy director, Gynecologic Oncology Department, Chaim Sheba Medical Center, Tel Aviv, Israel, said in their poster presentation during the meeting. “Only 1.7% of patients had grade 3 or higher AEs that occurred after ≥2 years of therapy.”

Olaparib demonstrated significant efficacy as maintenance treatment in the phase II Study 19 trial and the phase III SOLO2 study. In SOLO2, maintenance treatment with olaparib reduced the risk of progression or death by 70% compared with placebo; the median progression-free survival was 19.1 months with olaparib versus 5.5 months with placebo (P <.0001) in patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer.² In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of BRCA status.³

In SOLO2, patients were randomized 2:1 to olaparib as a 300-mg tablet twice daily (n = 196) or placebo (n = 99). All patients had relapsed ovarian cancer, confirmed BRCA1/2 mutation, and responded to their most recent platinum-containing regimen following 2 or more prior systemic regimens. Grade ≥3 AEs were reported for 36.9% of patients treated with olaparib tablets versus 18.2% with placebo. The most common nonhematologic AEs for olaparib were nausea (75.9%) and fatigue/asthenia (65.6%), and the incidence of grade ≥3 hematologic AEs included anemia (19.5%) and neutropenia (5.1%). The authors noted that 11.1% of patients in Study 19 stayed on treatment for at least 6 years.

The analysis presented at the 2018 ESMO Congress analyzed the safety and tolerability of olaparib in SOLO-2. AEs were graded by the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Sixty-two (31.8%) of the 195 patients treated with olaparib in SOLO-2 at the primary data cutoff received olaparib for >1 to <2 years and 59 (30.3%) for ≥2 years. The median treatment durations were 89.6 and 117.7 weeks, respectively.

In patients receiving treatment or placebo for >1 to <2 years, an AE of any grade was experienced by 87.1% on olaparib and the entire placebo group during this time. Among the patients who received olaparib or placebo for ≥2 years, 39.0% of the olaparib group and 22.2% of the placebo group had an AE, with onset reported during that time period. Most AEs were grade 1/2 regardless of when maintenance treatment began.

The dose interruption rate caused by AEs was 22.6% among patients who received olaparib for >1 to <2 years and 6.8% among those receiving it for ≥2 years. The most common reasons for dose interruption due to an AE were anemia in 12.9% and vomiting in 3.2% during the second year of olaparib and abdominal pain in 3.4%, respectively.

Dose reductions were more common during the first year of treatment. For patients with onset of AEs during the second year, 4 patients had a dose reduction due to a hematologic AE and 4 discontinued treatment because of an AE. Acute myeloid leukemia, decrease in neutrophil count, muscular weakness, and depression and disturbance in attention was experienced by the same patient. No patient who reported an AE after ≥2 years of olaparib required a dose reduction, discontinued treatment, or died due to AEs.

In the patients who received olaparib for >1 to <2 years, 83.9% had AEs ongoing at the start of the second year of treatment, including 14.5% with grade ≥3 AEs and 1.6% with a serious AE. The most common AEs that were ongoing at the start of the second year of olaparib were fatigue (29.0%), nausea (25.8%), anemia (19.4%), asthenia (16.1%), and headache (11.3%).

In the patients who received olaparib for >1 to <2 years, 83.9% had AEs ongoing at the start of the second year of treatment, including 14.5% with grade ≥3 AEs and 1.6% with a serious AE. The most common AEs that were ongoing at the start of the second year of olaparib were fatigue (29.0%), nausea (25.8%), anemia (19.4%), asthenia (16.1%), and headache (11.3%).

After ≥2 years of olaparib, the most common AEs were anemia (19.4%), nausea (17.7%), and vomiting (14.5%). The most common AEs with onset after ≥2 years were diarrhea (8.5%), abdominal pain (5.1%), and upper abdominal pain (5.1%).

References

1. Korach J, Freyer G, Banerjee S, et al. Long-term tolerability of olaparib tablets as maintenance therapy for platinum-sensitive relapsed ovarian cancer (PSR OC): phase III SOLO2 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract 952P. academic.oup.com/annonc/article/29/suppl_8/mdy285.160/5141893.
2. Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 Investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;18(9)1274-1284. doi: 10.1016/S1470-2045(17)30469-2.
3. Gourley C, Friedlander M, Matalonis U, et al. Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol. 2017;35(suppl; abstr 5533). doi: 10.1200/JCO.2017.35.15_suppl.5533.