The addition of 1 year of the PARP inhibitor olaparib after completion of standard neoadjuvant or adjuvant chemotherapy, surgery and any radiation therapy needed, significantly improved invasive disease-free (IDFS) and distant disease-free survival (DDFS) in patients with BRCA1/2 germline mutations and high-risk early-stage breast cancer that is negative for human epidermal growth factor receptor 2-(HER2), according to new research to be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
In the U.S., 5-10% of breast cancers are related to an inherited gene mutation.
Patients with newly diagnosed breast cancers associated with these mutations can present with aggressive, high risk disease.
Following completion of multi-modality therapy, which includes surgery, radiation, and chemotherapy, recurrence rates can remain high.
There is an unmet need to identify additional novel and effective therapies.
Olaparib is an oral targeted therapy - a poly (ADP-ribose) polymerase (PARP) inhibitor - that is already approved for patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer.
The randomised, double-blind phase III OlympiA study enrolled 1,836 patients with high-risk early breast cancer that was negative for human epidermal growth factor receptor 2-(HER2) and had germline BRCA1 or BRCA2 mutations, including triple negative and hormone receptor positive breast cancer.
All participants had already received standard adjuvant or neoadjuvant chemotherapy, surgery and radiation therapy if needed for early-stage breast cancer disease.
Participants were selected based on defined pathological selection criteria that were different in triple negative and hormone receptor positive breast cancer but were designed to exclude patients at lower risk of invasive disease recurrence.
Patients were randomised to receive either olaparib or placebo for 1 year.
The primary endpoint was IDFS; secondary endpoints were DDFS and OS.
The study has reported early at a median follow up of 2.5 years after a planned interim analysis that was reviewed by an independent Data Monitoring Committee.
OlympiA is an academia-industry partnership trial, being coordinated worldwide by the Breast International Group (BIG), in partnership with Frontier Science & Technology Research Foundation (FSTRF), NRG Oncology (National Cancer Institute-supported National Clinical Trials Network Group) and the study sponsors.
In the OlympiA study, patients who received standard treatment plus placebo had an estimated 3-year IDFS - being alive and free of recurrent invasive breast cancer and new second cancers - of 77.1%.
With the additional administration of 1 year of the oral PARP inhibitor olaparib, the estimated 3-year IDFS was improved to 85.9%.
The estimated 3-year DDFS was also improved from 80.4% with placebo to 87.5% with olaparib.
While 3-year estimated overall survival (OS) was greater with olaparib, the difference was not statistically significant at the time of this interim analysis at 2.5 years median follow up.
Adverse events (AEs) were consistent with those previously reported with olaparib treatment.
Serious adverse events (SAEs) did not occur more frequently with olaparib than with placebo.
“The OlympiA study results, the first reporting the effects of a PARP inhibitor as an “adjuvant therapy” on survival endpoints, suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation-associated early breast cancer who have levels of recurrence risk requiring neoadjuvant or adjuvant chemotherapy” said lead author Professor Andrew Tutt, MB ChB, PhD, FMedSci who is the Head of the Division of Breast Cancer Research and Director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London and the Breast Cancer Now Research Unit at Guy’s Hospital King’s College London.
The OlympiA trial is the first phase III study to report the effect of a PARP inhibitor in any adjuvant setting and in this context is focused on patients with germline BRCA1 or BRCA2 mutations and early-stage, high-recurrence risk breast cancer, following completion of standard multi-modality therapy, which includes a combination of chemotherapy drugs.
“OlympiA’s findings highlight the need for genetic testing for BRCA mutations in patients diagnosed with high-risk early-stage breast cancer. These results could have an important impact on treatment decisions for this patient population, possibly including the use of a PARP inhibitor in the adjuvant setting,” said ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
The patients in the study continue to be followed up for effects on overall survival and long-term safety endpoints.