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).
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.
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: 952P
Long-term AE data for olaparib tablets as maintenance therapy
|Group 1 (n = 62)||Group 2 (n = 59)|
|AEs with onset reported during the second yr (≥1–<2 yrs) of olaparib treatment||AEs with onset reported after ≥2 yrs of olaparib treatment|
|AE (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)||0|
|Treatment discontinuation caused by AE, n (%)||4 (6)||0|
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.
Legal entity responsible for the study
Editorial assistance was provided by Rachel Patel, Mudskipper Business Limited, funded by AstraZeneca.
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.