Olaparib Suitable For Long-term Maintenance in Recurrent Ovarian Cancer

Jacob Korach, MD

Jacob Korach, MD

The side effect profile of olaparib tablets and the low rate of treatment discontinuation make it suitable for maintenance treatment for patients with platinum-sensitive recurrent ovarian cancer, according to safety assessments from the SOLO-2 trial.

Most adverse events (AEs) with olaparib are low grade, were not serious, and occurred within the first year of treatment. &ldquo;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,&rdquo; investigators led by Jacob Korach, MD, deputy director, Gynecologic Oncology Department, Chaim Sheba Medical Center, Tel Aviv, Israel, concluded in their poster presentation at the 2018 ESMO Congress. &ldquo;Only 1.7% of patients had grade &ge;3 AEs that occurred after &ge;2 years of therapy.&rdquo;¹

Olaparib demonstrated significant efficacy as maintenance treatment in the phase II Study 19 trial and the phase III SOLO-2 study. In SOLO2, maintenance treatment with olaparib reduced the risk of progression or death by 70% compared with placebo (median progression-free survival: 19.1 months vs 5.5 months;P< .0001) in patients with platinum-sensitive, relapsed,BRCA-mutant ovarian cancer.²In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of&nbsp;BRCAstatus.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&nbsp;BRCA1/2mutation, and were in response to their most recent platinum-containing regimen following 2 or more prior systemic regimens. Grade &ge;3 AEs were reported for 36.9% of patients treated with olaparib tablets versus 18.2% with placebo. The most common non-hematologic AEs for olaparib were nausea (75.9%) and fatigue/asthenia (65.6%). The incidence of grade &ge;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 &ge;6 years.

The analysis presented here analyzed the safety and tolerability of olaparib in SOLO-2. AEs in were graded by the National Cancer Institute&rsquo;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 cut-off received olaparib for >1 to <2 years and 59 (30.3%) for &ge;2 years. Median treatment duration was 89.6 weeks in those in the former group and 117.7 weeks for those in the latter.

In the patients receiving treatment or placebo for >1 to <2 years, an AE of any grade was experienced by 87.1% of olaparib recipients and by 100% of the placebo group during this time. Among the patients who received olaparib or placebo for &ge;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.

Dose interruption caused by AEs occurred at a rate of 22.6% among patients who received olaparib for >1 to <2 years and 6.8% among those receiving it for &ge;2 years. The most common reason for dose interruption due to an AE were anemia in 12.9% and vomiting in 3.2% during the second year of olaparib in those receiving treatment for >1 to <2 years, and abdominal pain in 3.4% in those after &ge;2 years of treatment.

Dose reducitons 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 experienced by the same patient). No patient who reported an AE after &ge;2 years of olaparib required a dose reduction or discontinued treatment or died due to AEs.

In the patients who received olaparib for >1 to <years, 83.9% had AEs ongoing at the start of the second year of treatment, including 14.5% with grade &ge;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%).

The most common AEs with onset during the second year (in those receiving treatment for >1 to <2 years) after &ge;2 years of olaparib were anemia (19.4%), nausea (17.7%), and vomiting (14.5%). The most common AEs with onset after &ge;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. Presented at: ESMO 2018; October 19-23; Munich, Germany. 952P.
2. Pujade-Lauraine E, Ledermann JA, Selle F, et al. 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 [published online July 25].Lancet Oncol.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).