HRD+ tumors: first PARP inhibitor approved for first-line maintenance therapy

As the first and only PARP inhibitor, olaparib was recently approved by swissmedic for first-line maintenance therapy in patients with advanced, HRD-positive ovarian cancer. The addition of olaparib to bevacizumab resulted in a substantial improvement in progression-free survival (PFS) with a consistent safety profile in the pivotal study.

As the fifth leading cause of cancer death in women, ovarian cancer remains a major therapeutic challenge today. The five-year survival rate is only about 45%, which is particularly due to the often already advanced stage at diagnosis. It is precisely those patients whose tumor is already FIGO stage III or IV and homologous recombination deficiency (HRD) at the time of detection who can now benefit from improved maintenance therapy. Thus, olaparib is now approved in Switzerland in combination with bevacizumab for this indication in high-grade serous ovarian cancer. The prerequisite is complete or partial remission following first-line chemotherapy combined with bevacizumab.

One in two women with advanced ovarian cancer suffers from an HRD-positive tumor. Homologous recombination deficiencies encompass a broad spectrum of genetic alterations, including BRCA mutations. All women with a BRCA mutation are HRD positive, but the BRCA mutation is not the only cause of homologous recombination deficiency. By expanding the first-line indication for olaparib beyond BRCA-positive tumors, Lynparza® can now be used in patients who have other genetic aberrations.

In the pivotal Phase III PAOLA-1 trial, a median progression-free survival of 37.2 months was observed with combination maintenance therapy with olaparib and bevacizumab, compared with 17.7 months with bevacizumab treatment alone. In HRD-positive advanced ovarian cancer, the risk of disease progression or death was reduced by 67% using combination therapy. While these results were already published in The New England Journal of Medicine in 2019, more interesting data were added at the 2020 European Society for Medical Oncology (ESMO) Virtual Annual Congress. Thus, the addition of olaparib to maintenance therapy showed benefit beyond the first disease progression and statistically significantly prolonged the duration to the second disease progression. This was delayed by a median of 15 months with the additional medication.

Of all PARP inhibitors, olaparib has the broadest and most advanced clinical development program. With the new approval extension, another important step has been taken in the treatment of ovarian cancer. We are looking forward to further results from the various studies.

Source: press release “Lynparza® (olaparib) in combination with bevacizumab approved in Switzerland for first-line maintenance therapy in advanced ovarian cancer with homologous recombination deficiency (HRD),” 1. December 2020, AstraZeneca AG, Baar, Switzerland and MSD Merck Sharp & Dohme AG, Lucerne.