Secondary OPINION analysis boosts safety profile of maintenance olaparib for ovarian cancer

In women with platinum-sensitive relapsed ovarian cancer without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (non-gBRCAm), maintenance olaparib was well tolerated, according to the secondary safety results from the phase IIIb OPINION study presented at SGO 2022.

Olaparib has shown efficacy for preventing the worsening of ovarian cancer that has spread beyond the ovaries, particularly in women with a germline mutation in one of two genes (collectively known as BRCA genes). [N Engl J Med 2012;366:1382-1392; Lancet Oncol 2017;18:1274-1284] In the initial OPINION analysis however, olaparib was also reportedly effective among non-gBRCAm patients who had previously benefited from at least two lines of prior platinum-based chemotherapy. [Gynecol Oncol 2022;164:498-504]

“[We therefore conducted a secondary safety analysis] to further characterize the safety and tolerability profile of maintenance olaparib in this patient setting,” said presenting author Dr Nicoletta Colombo from the IEO Istituto Europeo di Oncologia, IRCCS, and University of Milan-Bicocca, Milan, Italy.

In OPINION, 279 women aged 40–85 years received maintenance olaparib 300 mg tablets BID. They were treated until disease progression or unacceptable toxicity. [SGO 2022, abstract 128]

At the primary data cutoff, 75 percent of participants discontinued olaparib, primarily owing to disease progression (63 percent). The median total and actual treatment durations were similar (9.4 and 9.2 months, respectively). “Dose interruptions did not have a big impact on treatment duration,” said Colombo and colleagues.

The most common any-grade adverse events (AEs) were nausea (48 percent), fatigue/asthenia (44 percent), anaemia (39 percent), vomiting (16 percent), and neutropenia (16 percent). Nonetheless, during the first 18 months following olaparib initiation, the nausea, fatigue/asthenia, and vomiting events were mostly grade 1 in severity. Neutropenia events* were mostly grade 1/2, while anaemia events** were mostly grade 1–3.

Seven AEs of special interest have been reported in six participants, two of which occurring in one patient (breast cancer and pneumonitis). The other events were rectal adenocarcinoma, lung infiltration, another case of pneumonitis, and two cases of myelodysplastic syndrome. One AE – aspiration pneumonia – was deemed fatal but unrelated to treatment.

“[In summary,] the most common AEs generally occurred early,” said the investigators. “[The majority] of AEs were low grade, with only one grade ≥3 anaemia reported in >10 percent of patients … Most side effects were mild (requiring no treatment) or moderate (requiring minimal, local, or noninvasive treatment).”

Less than a quarter of the participants had dose reductions owing to AEs, and discontinuation rate due to AEs was low (8 percent).

“[Taken together, our] safety assessment showed that maintenance olaparib was well tolerated and the safety profile was consistent with that observed in prior olaparib studies,” the researchers concluded.