Long-Term Tolerability of Olaparib Tablets as Maintenance Therapy for Platinum-Sensitive Relapsed Ovarian Cancer

The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is available as a capsule and as a tablet, with both formulations having shown significant efficacy as maintenance therapy for patients with platinum-sensitive relapsed (PSR) ovarian cancer, and especially for those with BRCA mutations.1,2 The long-term tolerability of olaparib capsules has been previously established, with 11.1% of patients staying on treatment for 6 years,3 although a similar assessment has not been made for the tablet form. Here, Korach and colleagues evaluated the long-term tolerability of olaparib tablets used as maintenance therapy in patients with BRCA-mutated PSR ovarian cancer (the SOLO2 trial).4

At the primary data cutoff (September 19, 2016), a total of 195 patients had been treated with olaparib; 62 (32%) had received olaparib for 1 to <2 years (Group 1) and 59 (30%) for 2 years (Group 2). Ninety-nine patients received maintenance placebo in the study, with 12 (12%) and 9 (9%) belonging to Group 1 and Group 2, respectively. Most adverse events (AEs) that began after 1 years (Group 1) or 2 years (Group 2) were grade 1 or grade 2, with few serious AEs (n = 14 [11%] and n = 1 [2%], respectively). The most common AEs with onset during the second year of olaparib treatment were anemia (19%), nausea (18%), and vomiting (15%). The most common AEs with onset after 2 years were diarrhea (8%), abdominal pain (5%), and upper abdominal pain (5%). Four patients in Group 1 discontinued olaparib because of AEs (acute myeloid leukemia, decreased neutrophil count, muscular weakness, disturbance in attention, and depression; all n = 1) versus no patients in Group 2.

The results reported in this study are consistent with the known safety profile of olaparib, with the observed AEs being mostly low grade, nonserious, and associated with a low rate of treatment discontinuation. Most toxicities with olaparib treatment occurred within the first year of therapy, and the incidence of AEs was lower during the second year. The authors of the study conclude that olaparib tablets are suitable for long-term maintenance therapy for PSR ovarian cancer patients, without cumulative toxicity and with few late-onset AEs.

References

  1. Ledermann J, et al. Lancet Oncol. 2014;15(8):852-61.
  2. Pujade-Lauraine E, et al. Lancet Oncol. 2017;18(9):1274-1284.
  3. Gourley C, et al. ASCO 2017. Abstract 5533.
  4. Korach J, et al. ESMO 2018. Abstract 952P.