Long-term tolerability of olaparib tablets as maintenance therapy for platinum-sensitive relapsed ovarian cancer (PSR OC): Phase III SOLO2 trial (2018)

Background: The PARP inhibitor olaparib (Lynparza®) has shown significant efficacy as maintenance therapy for patients (pts) with PSR OC, especially pts with BRCA mutations, as capsules (Ledermann et al Lancet Oncol 2014) and tablets (Pujade-Lauraine et al Lancet Oncol 2017). Olaparib capsules have shown long-term benefit, with pts staying on treatment for ≥5 years (yrs; Gourley et al ASCO 2017). We analysed the long-term tolerability of olaparib tablets in the SOLO2 trial (ENGOT-Ov21; NCT01874353). Methods: In SOLO2, pts with BRCA-mutated PSR OC in response to platinum received maintenance olaparib tablets (300 mg bid) or placebo until disease progression. Adverse events (AEs) were graded by CTCAE v4.0. Results: At the primary data cut-off (DCO; 19 Sep 2016), of 195 pts treated with olaparib, 62 (32%) had received olaparib for ≥1–<2 yrs (Group 1) and 59 (30%) for ≥2 yrs (Group 2), vs 12/99 (12%) and 9/99 (9%), respectively, who received placebo. Most AEs that began after ≥1 yr (Group 1) or ≥ 2 yrs (Group 2) were grade 1–2, with few serious AEs (Table). The most common AEs with onset during the second yr of olaparib treatment were anaemia (19%), nausea (18%), and vomiting (15%). The most common AEs with onset after ≥2 yrs were diarrhoea (8%), abdominal pain (5%), and upper abdominal pain (5%). Four pts in Group 1 discontinued olaparib because of AEs (acute myeloid leukaemia, decreased neutrophil count, muscular weakness, disturbance in attention and depression; all n = 1) vs no pts in Group 2.Table: 952PLong-term AE data for olaparib tablets as maintenance therapyGroup 1 (n = 62)Group 2 (n = 59)AEs with onset reported during the second yr (≥1–<2 yrs) of olaparib treatmentAEs with onset reported after ≥2 yrs of olaparib treatmentAE (any grade), n (%)54 (87)23 (39)AE (grade ≥3), n (%)11 (18)1 (2)Serious AE, n (%)7 (11)1 (2)Dose interruption caused by AE, n (%)14 (23)4 (7)Dose reduction caused by AE, n (%)4 (6)0Treatment discontinuation caused by AE, n (%)4 (6)0 Open table in a new tab Conclusions: AEs reported during long-term olaparib maintenance therapy were mostly low grade, non-serious and associated with a low rate of treatment discontinuation. Common AEs were consistent with the known safety profile. Olaparib tablets are suitable for long-term maintenance therapy for PSR OC pts, without cumulative toxicity and with few late-onset AEs. Clinical trial identification: NCT01874353, January 2017. Editorial acknowledgement: Editorial assistance was provided by Rachel Patel, Mudskipper Business Limited, funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: J. Korach: Advisory board member: AstraZeneca Israel. G. Freyer: Board and speaker fees: AstraZeneca, Pfizer, Lilly, Novartis, Biogaran, Clovis, Amgen; Speaker fees: Roche; Research funding: AstraZeneca, BMS, Amgen; Consultant honoraria: Amgen. S. Banerjee: Honoraria: AstraZeneca, Tesaro, Clovis, PharmaMar, and Gamamabs; Research funding to institution: AstraZeneca. J. Cosin: Consultant for Medtronic. A.M. Oza: Steering committees (non-compensated) for trials: AstraZeneca, Clovis, Tesaro; Honoraria: Intas Pharma. A.M. Poveda: Advisor: AstraZeneca, Roche, Tesaro, Clovis, PharmaMar. C. Scott: Personal fees and non-financial support: AstraZeneca; Grants, personal fees, non-financial support, and others: Clovis Oncology, Roche; Others: Eisai Australia, Beigene. M. Lapresa: Fees: AstraZeneca, PharmaMar. G.S. Sonke: Institutional research support: AstraZeneca, Merck, Novartis, Roche. S. Tjulandin: Honoraria: AstraZeneca, Pfizer, Eli Lilly, MSD, Hoffmann La Roche. I.B. Vergote: Advisory board fees: Roche, Genmab, Advaxis, Morphotek, Hoffmann La Roche, Cerulean Pharma, Novocure, AstraZeneca, Mateon Therapeutics, Immunogen, Eli Lilly Benelux, Amgen, Theradex Europe, Pfizer, Debiopharma International, Vifor Pharma, Novartis, MSD, Janssen-Cilag, Bayer, Clovis Oncology, Takeda, PharmaMar, Oncoinvent; Research grants: Amgen, Roche; Accommodation and travel expenses: Tesaro, Clovis Oncology, Takeda, PharmaMar, Roche, Genmab, Oncoinvent; Institutional research grants: Morphotek. S. Turner: Employee of AstraZeneca and owns stock. E. Pujade-Lauraine: Honoraria, advisory board member: AstraZeneca, Roche, Tesaro, Clovis, Pfizer. All other authors have declared no conflicts of interest.