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Single-agent olaparib generated similar overall survival compared with non-platinum chemotherapy in heavily pretreated patients with platinum-sensitive, relapsed ovarian cancer with BRCA mutations, according to the final analysis of the phase 3 SOLO3 trial.
Single-agent olaparib (Lynparza) generated similar overall survival (OS) compared with non-platinum chemotherapy in heavily pretreated patients with platinum-sensitive, relapsed ovarian cancer with BRCA mutations, according to the final analysis of the phase 3 SOLO3 trial (NCT02282020) presented at the 2022 SGO Annual Meeting on Womens’ Cancer.1
At a median follow-up of 48.9 months in patients who received olaparib monotherapy, the median OS was 34.9 months. At a median follow-up of 25.4 months, patients who were administered chemotherapy experienced a median OS of 32.9 months (HR, 1.07; 95% CI, 0.76-1.49; P = .714).
“Twenty-five percent of [patients who received] chemotherapy vs 11% of [patients who received] olaparib withdrew from the study prior to death,” lead study author Richard T. Penson, MD, MRCP, clinical director, Medical Gynecologic Oncology, Medicine, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, said in the presentation. “The survival status of some of these patients is unknown, which may contribute to the lower instance of death in the chemotherapy group.”
In 2014, olaparib received an FDA approval for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have received at least 3 prior lines of chemotherapy.2 SOLO3 enrolled a similar population of patients who progressed on 2 or more prior lines of chemotherapy.
SOLO3, a 2:1 randomized trial, enrolled 266 patients with platinum-sensitive, relapsed, high-grade serious or endometroid ovarian, primary peritoneal and/or fallopian tube cancer who harbored germline BRCA mutations. Patients were required to have an ECOG performance status between 0 and 2, at least 2 prior lines of platinum-based chemotherapy, and no prior PARP inhibitor therapy.
Patients in the olaparib arm (n = 178) received 300 mg of the PARP inhibitor twice daily, and patients in the non-platinum chemotherapy arm (n = 88) received either pegylated liposomal doxorubicin (PLD; n = 47), paclitaxel (n = 20), gemcitabine (n = 13), or topotecan (n = 8).
The primary end point of the trial was objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 criteria. Secondary end points included OS, progression-free survival (PFS), second PFS, time to first subsequent treatment (TFST), time to second subsequent treatment (TSST), time to treatment discontinuation or death (TDT), health-related quality of life, and safety.
In the olaparib arm, 51.7% of patients received 2 prior lines of chemotherapy, 23.0% received 3 lines, and 25.3% received 4 or more lines. Additionally, 64.0% of patients were partially platinum sensitive and 36.0% were platinum sensitive. Furthermore, 67.4% of patients had BRCA1-mutated disease, 28.1% had BRCA2-mutated disease, 1.1% were negative on Myriad testing, and 3.4% had missing BRCA-mutation status.
Prior analysis of SOLO3 showed olaparib generated an ORR per BICR of 72% vs 51% with chemotherapy.3 Furthermore, the median PFS per BICR in the olaparib group was 13.4 months compared with 9.2 months in the chemotherapy group, reducing the risk of disease progression or death by 38% (HR, 0.62; 95% CI, 0.43-0.91; P = .013).
Updated data from the final analysis showed patients in the olaparib arm achieved a median second PFS of 23.6 months vs 19.6 months in the chemotherapy arm (HR, 0.80; 95% CI, 0.56-1.15; P = .229). The median TFST was 15.4 months in the olaparib arm vs 10.9 months in the chemotherapy arm (HR, 0.49; 95% CI, 0.35-0.69; P < .001). Additionally, the median TSST with olaparib was 25.2 months vs 19.9 months with chemotherapy (HR, 0.75; 95% CI, 0.53-1.05; P = .089). The median TDT was 13.1 months in the olaparib group vs 5.1 months in the chemotherapy group (HR, 0.20; 95% CI, 0.14-0.29; P < .001).
At the time of data cutoff, 11% of patients in the olaparib arm remained on treatment compared with no patients in the chemotherapy arm. Patients discontinued study treatment because of disease progression (72% and 34% in the olaparib and chemotherapy arms, respectively); adverse effect ([AE] 10% and 17%); patient decision (4% and 11%); severe protocol non-compliance (1% and 0%); study-specific discontinuation criteria (0% and 2%); clinical progression or death (3% and 3%); investigator decision (not evaluable [NE] and 10%); and the completion of chemotherapy (NE and 8%).
No new safety signals were generated in the final OS analysis. Treatment-emergent AEs (TEAEs) occurred in 98.3% of patients in the olaparib arm vs 96.1% in the chemotherapy arm. Moreover, 52.8% of patients receiving olaparib had a grade 3 or higher TEAE compared with 48.7% of patients in the chemotherapy arm. The rates of serious AEs were 25.8% vs 18.4%, respectively. TEAE-related dose interruptions, dose reductions, and treatment discontinuation occurred in 50.0% vs 42.1%, 29.8% vs 32.9%, and 10.1% vs 19.7% of patients in the olaparib and chemotherapy arms, respectively.
The most common TEAEs were nausea (64.6% and 34.2% in the olaparib and chemotherapy arms, respectively), anemia (52.8% and 25.0%), fatigue/asthenia (52.8% and 42.1%), vomiting (38.2% and 22.4%), diarrhea (29.2% and 17.1%), neutropenia (24.2% and 42.1%), abdominal pain (23.0% and 14.5%), headache (16.3% and 11.8%), constipation (13.5% and 22.4%), thrombocytopenia (12.4% and 11.8%), alopecia (6.2% and 15.8%), stomatitis (4.5% and 18.4%), peripheral neuropathy (2.8% and 10.5%), and palmar-plantar erythrodysesthesia (0.6% and 35.5%).
Notably, 6 patients presented with BRCA2 reversion mutations at baseline. Among those patients, no responses with olaparib were observed, with a best response of stable disease. Further research is warranted in these patients, Penson noted.