Maintenance therapy with the PARP inhibitor olaparib (Lynparza) extends progression-free survival by an unprecedented three years in women with advanced ovarian cancer and a BRCA mutation, results from the phase 3 SOLO-1 trial show.
Presented at the European Society for Medical Oncology (ESMO) Congress in Munich, results from the study suggest a 70% lower risk of disease progression or death with olaparib than with placebo [HR 0.30].
A secondary finding of the trial was also encouraging, showing that when ovarian cancer did recur, the second round of treatment with chemotherapy was successful and was not affected by having taken olaparib.
“That provides further reassurance that olaparib is best used following first-line therapy as opposed to later lines of therapy,” said lead investigator Associate Professor Kathleen Moore an oncologist at the Stephenson Cancer Center, University of Oklahoma.
The SOLO-1 trial was conducted in several international centres and co-investigators included Professor Michael Friedlander at the University of NSW Clinical School, Prince of Wales Hospital, Sydney.
In the study, 391 women with high grade serous or endometrioid ovarian cancer (FIGO stage III–IV) who were in clinical complete or partial response after platinum-based chemotherapy were randomised to maintenance therapy with olaparib tablets 300 mg bd (n=260) or placebo (n=131) for two years.
According to Professor Moore, the median PFS for patients who received placebo was only 13.8 months while the median PFS after follow-up of 41 months for those who received olaparib was not reached but looked to be approximately three years longer than the placebo group.
“This study demonstrates an outstanding improvement in PFS over placebo which is maintained even after the olaparib is stopped at two years,” she said.
“While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50% of women on the olaparib arm were still progression free at four years as compared to only 11% for placebo speaks to this hope,” she said.
The secondary outcome, PFS2, was significantly improved among patients who had received olaparib maintenance with a median PFS2 of 41.9 months for placebo versus median not reached for the olaparib group (HR: 0.50).
The most common grade ≥3 toxicities with olaparib were anaemia (22%) and neutropenia (8%), while 12% of patients discontinued olaparib due to toxicity and not disease progression.
“These are outstanding results in a worsening disease setting. Not only was olaparib efficacious but it was also shown to be well tolerated,” commented Prof Isabelle Ray-Coquard, from Université Claude Bernard Lyon Est, Lyon, France at ESMO.
“The findings promise to change practice in this subgroup of patients with a BRCA mutation.”
A key question now is whether this benefit extends to all high-grade serous carcinomas, said Professor Ray-Coquard.
“Also, what is the best maintenance therapy? Standard first line therapy in many countries is chemotherapy plus bevacizumab maintenance for the majority of advanced disease, but the question remains whether maintenance with olaparib alone, or in combination with bevacizumab is preferable. The PAOLA 1 trial will provide some information, and will probably be available next year,” she added.
The results are published simultaneously in NEJM.
Olaparib was first listed on the PBS for treatment of ovarian cancer in 2017.