Niraparib Prolongs Progression-Free Survival Without Toxicity in Ovarian Cancer
May 29, 2020 01:30pm
By Danielle Ternyila
“In the final SOLO2 analysis, maintenance olaparib provided a clinically meaningful improvement of 12.9 months [in] median overall survival. These results demonstrate that olaparib maintenance monotherapy not only delays disease progression but also improves overall survival in women with platinum-sensitive ovarian cancer and a BRCA mutation.”
Maintenance treatment with olaparib (Lynparza) demonstrated an improved median overall survival (OS) of 12.9 months over placebo in patients with platinum-sensitive relapsed ovarian cancer harboring a BRCA1/2 mutation, according to final OS results from the phase III SOLO2/ENGOT-ov21 trial.1
“In the final SOLO2 analysis, maintenance olaparib provided a clinically meaningful improvement of 12.9 months [in] median overall survival,” said lead author Andrés Poveda, MD, of Initia Oncology, Hospital Quironsalud, in Valencia, Spain. “These results demonstrate that olaparib maintenance monotherapy not only delays disease progression but also improves overall survival in women with platinum-sensitive ovarian cancer and a BRCA mutation.”
Poveda presented updated survival results after approximately 5 years of follow-up in a press briefing ahead of the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting.
Olaparib was approved by the FDA in August 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. The approval was based on earlier findings from the SOLO2 trial.
The trial enrolled patients with relapsed high-grade serous ovarian cancer or endometrioid cancer who had a BRCA mutation. Patients had received at least 2 prior lines of platinum-based chemotherapy and were in a complete or partial response to their most recent platinum regimen.
Participants were randomized 2:1 to receive 300 mg olaparib tablets twice daily (n = 196) or placebo (n = 99), and treatment continued until disease progression occurred.
In the primary analysis of the primary end point, maintenance olaparib led to a median progression-free survival (PFS) benefit of 13.6 months over placebo (19.1 vs 5.5 months; HR, 0.30; 95% CI, 0.22-0.41; P <.0001).2
“SOLO2 was the first randomized phase III trial to provide overall survival data on PARP maintenance therapy,” Poveda noted.
The final analysis for OS was planned for at 60% data maturity after about 177 events. Follow-up continued for a median of 65.7 months in the olaparib arm and for 64.5 months in the placebo arm with a data cutoff of February 3, 2020. The median OS, unadjusted for crossover, was 51.7 months with olaparib versus 38.8 months with placebo (HR< 0.74; 95% CI, 0.54-1.00; P = .0537).1
At 5 years, 42.1% of patients in the olaparib group were still alive compared with 33.2% in the placebo group. However, 39% of patients in the placebo arm crossed over to receive PARP inhibition.
In a subgroup of patients with germline BRCA mutations, as identified by the Myriad BRACAnalysis CDx assay, the median OS in those who received olaparib (n = 190) was 52.4 months versus 37.4 months in those who received placebo (n = 96) (HR, 0.71; 95% CI, 0.52-0.97; P = .0306).
A total of 195 patients in the olaparib arm were included in the safety analysis set and 22% of patients in the olaparib arm were exposed to treatment for at least 5 years compared with 9% in the placebo group.
“Finding that 22% of patients in the olaparib group received the study treatment for more than 5 years is impressive in the setting of relapsed ovarian cancer,” Poveda commented.
Long-term tolerability was consistent with prior reports for the safety profile of olaparib. The most common treatment-emergent adverse events (TEAEs) were nausea, fatigue/asthenia, and anemia. Anemia was also the most common grade 3 or higher TEAE.
TEAEs led to dose interruptions in 50% of patients in the olaparib group and 19% in the placebo group; dose reductions were required in 28% and 3% of olaparib- and placebo-treated patients, respectively. Treatment discontinuations due to TEAEs were reported in 17% of patients in the olaparib arm and in 3% of patients in the placebo group.
“This study confirms that the PARP inhibitor olaparib should be the standard maintenance therapy for patients with BRCA-related relapsed ovarian cancer responding to platinum-based chemotherapy – a significant advance for women with a cancer that has a historically poor prognosis,” ASCO chief medical officer and executive vice president Richard L. Schilsky, MD, FASP, FSCT, FASCO, commented in a press release.3