Introduction

Relapsed advanced ovarian cancer is typically incurable, emphasizing the need for effective first-line treatments that delay relapse, prolong survival, and enhance the potential for cure.

Aim

To report Overall Survival (OS) with maintenance olaparib in SOLO1 patients with newly diagnosed advanced BRCA-mutated ovarian cancer after a 7-year follow-up

Patient Profile

Patients with newly diagnosed advanced ovarian cancer and a BRCA mutation

Methods

• Double-blind phase III trial
• Patients were randomly assigned (2:1) to receive olaparib (300 mg twice daily) tablets (n=260) or placebo (n=130) within 8 weeks of receiving their last dose of chemotherapy.

Study Outcomes

• OS (defined as the time from random assignment to death because of any cause)
• Time from random assignment to first subsequent therapy or death (TFST)
• Time from random assignment to second subsequent therapy or death (TSST)
• Time from random assignment to discontinuation of study treatment or death (TDT)
• Safety and tolerability

Results

• The hazard ratio for OS was 0.55 (P = .0004 [ P= .0001 required to declare statistical significance]).

  Figure 1: Overall survival outcomes

  

   

  Table 1: Time for subsequent therapy with PARP inhibitor

  Time for event	Olaparib	Placebo	HR
  TFST (Months)	64.0	15.1	0.37 (0.28 to 0.48)
  TSST (Months)	93.2	40.7	0.50 (0.37 to 0.67)
  TDT (Months)	24.6	13.8	0.63 (0.51 to 0.78)

   

   

• More than 40% of placebo patients vs 14.6% of olaparib patients received subsequent therapy with a PARP inhibitor (and 59.8% of placebo patients v 31.1% of olaparib patients who received any subsequent therapy received a PARP inhibitor)

  Table 1: Subsequent PARP Inhibitor Therapy

  Patients Receiving PARP Inhibitor	Olaparib (n=260) (%)	Placebo (n=131) No (%)
  Subsequent PARP inhibitor (any line)	14.6	44.3
  First subsequent therapy	5.8	24.4
  Second subsequent therapy	5.4	13.0
  Third subsequent therapy	2.7	3.8
  Fourth subsequent therapy	0	2.3
  Fifth subsequent therapy	0.8	0.8

  PARP: poly (ADP-ribose) polymerase

   

• The incidence of myelodysplastic syndrome and acute myeloid leukaemia remained low, and new primary malignancies remained balanced between treatment groups.

  Safety

• After a 7-year follow-up
  • The safety profile of maintenance olaparib was consistent with the previously reported
  • Most common AEs (adverse events) were Nausea, fatigue/asthenia, vomiting, and anemia,
  • Most common grade 3 AE was anemia
  • Four (1.5%) cases of MDS/AML were reported in the olaparib group, and one (0.8%) case of MDS/AML was reported in the placebo group
  • New primary malignancies were reported in 14 (5.4%) olaparib patients vs in 8 (6.2%) placebo patients.

  Conclusion

• The study demonstrated that maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation resulted in clinically meaningful improvement in overall survival.
• The long-term follow-up showed no new safety signals.

Reference

J Clin Oncol. 2023 Jan 20;41(3):609-617