From the Journals

SOLO3: Olaparib outperforms chemo in heavily pretreated ovarian cancer



For heavily pretreated patients with BRCA-mutated ovarian cancer, olaparib is more effective than nonplatinum chemotherapy, according to results from the SOLO3 trial.

Both objective response rate and progression-free survival were significantly better in the olaparib group, reported lead author Richard T. Penson, MD, of Massachusetts General Hospital, Boston, and colleagues. These findings were published in the Journal of Clinical Oncology.

SOLO3 provides much-needed data for an understudied but common group of patients, according to Kathleen Moore, MD, lead author of the previous SOLO1 trial and associate director of clinical research at the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.

Dr. Kathleen Moore, University of Oklahoma

Dr. Kathleen Moore

“[Approximately] 50% of the women who participated in SOLO3 were on their fourth or more line of chemo,” Dr. Moore said in an interview. “That group of patients has not been studied in the past ... Even though we know many women receive many, many lines of chemotherapy, we really don’t have high quality clinical trial data to give women any indication of what to expect in terms of their response rate.”

SOLO3 is also notable, Dr. Moore said, because it is the first phase 3 trial to compare a PARP inhibitor with doctor’s choice chemotherapy.

SOLO3 involved 266 patients with BRCA-mutated, relapsed ovarian cancer who had received two or more lines of platinum-based chemotherapy. All patients were platinum sensitive (progression more than 12 months after last platinum-based treatment) or partially platinum sensitive (progression within 6-12 months of last platinum-based treatment).

After enrollment, participants were randomized in a 2:1 ratio to receive either olaparib (300 mg twice daily) or physician’s choice, single-agent, nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary endpoint was objective response rate, determined by blinded independent central review. Secondary endpoints included progression-free survival and overall survival.

At a median follow-up of 13.8 months in the olaparib group and 3.9 months in the chemotherapy group, olaparib showed a significant efficacy advantage. Among 223 patients with measurable disease, the objective response rate was 72.2% in the olaparib group and 51.4% in the chemotherapy group (odds ratio, 2.53; P = .002).

The superiority of olaparib was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Similar benefits were observed regardless of age.

Across all patients, the median progression-free survival was significantly better in the olaparib group, at 13.4 months, versus 9.2 months in the chemotherapy group (P = .013). Overall survival data were immature.

No new safety signals were encountered. The most common adverse events (AEs) in the olaparib group were nausea, fatigue/asthenia, anemia, vomiting, and diarrhea. The most common AEs in the chemotherapy group were fatigue/asthenia, palmar-plantar erythrodysesthesia, nausea, neutropenia, and anemia.

The rate of serious AEs was 23.6% in the olaparib group and 18.4% in the chemotherapy group. Three patients in the olaparib group, and none in the chemotherapy group, developed new primary malignancies. There were four patients with fatal AEs in the olaparib group (myelodysplastic syndrome, cardiopulmonary decompensation, sepsis, and acute myeloid leukemia and subarachnoid hemorrhage), and there was one fatal AE in the chemotherapy group (mesenteric vein thrombosis).

Dr. Moore pointed out that these findings are relevant to current clinical practice, but a shifting treatment landscape may soon render SOLO3 data obsolete.

“PARP [inhibitors] are likely moving into the frontline,” Dr. Moore said. “So this population of women who have not received a PARP [inhibitor] and are recurrent is still here, and they will be for several years, but there’s going to be a point when they’re not going to be here anymore, because they’ll all have received [a PARP inhibitor] front line.”

Concerning the broader research landscape for PARP inhibitors, Dr. Moore suggested that investigators are currently in a “waiting period” while the Food and Drug Administration and European Medicines Agency interpret major clinical trials, such as PAOLA-1 and PRIMA.

A variety of patient populations and clinical scenarios remain unevaluated, Dr. Moore said, including patients who don’t respond to PARP inhibitors, those who have disease recurrence while taking PARP inhibitors, and which drug combinations to use for which patients.

“There are a lot of irons in the fire right now, just getting ready to launch, but I think we need to see what the population is that’s going to be exposed to PARP [inhibitors] next, so we can design the next round of studies,” Dr. Moore said. “It’s an exciting time.”

SOLO3 was funded by AstraZeneca and Merck. The investigators reported additional relationships with Clovis Oncology, Eisai, Tesaro, and other companies. Dr. Moore disclosed relationships with Genentech, Immunogen, Mersana, and other companies.

SOURCE: Penson et al. J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745.

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