Several poly (ADP-ribose) polymerase (PARP) inhibitor therapies are currently under investigation to assess their potential for the management of breast cancer. Olaparib (Lynparza) is being evaluated in a Phase III study in HER2-ve mBC pts with a gBRCAm (OlympiAD; D0819C00003; NCT02000622). The prevalence of germline and somatic BRCA mutations or other somatic homologous recombination repair gene mutations (HRRm) in HER2-ve mBC pts is not well defined. Treatment and clinical outcomes data for pts with HRRm are also limited. The primary objective of this real-world evidence study (NCT03078036) is to estimate gBRCAm prevalence in a population of HER2-ve mBC pts not selected by phenotype, age or family history. Treatment patterns and survival outcomes for pts with HRRm will also be examined.
BREAKOUT is a prospective, cross-sectional, non-interventional, observational cohort study recruiting HER2-ve mBC pts who have started first-line chemotherapy within 90 days prior to enrollment. If hormone receptor positive, eligible pts will have exhausted all hormone therapy options prior to enrollment and will not have received prior PARP inhibitor treatment. If unavailable from medical records, gBRCAm status will be locally determined by blood test and, if negative, archival tumor specimens may be examined with a FoundationOne Dx genomic profile. Pts with a gBRCAm, somatic BRCA mutation or other HRRm (in ATM, RAD51B, RAD51C, RAD51D, RAD54L, BRIP1, FANCL, PALB2, BARD1, CHEK1, CHEK2, CDK12 or PPP2R2A) will be followed for ≥18 months to determine the distribution of standard-of-care treatments, progression-free survival (investigator assessed) and overall survival by line of therapy. Approximately 2000 women in 17 countries in North America, the EU and the Asia Pacific region will be enrolled to provide a global gBRCAm prevalence estimate with a precision of no more than ±2%. An interim analysis focusing on gBRCAm prevalence will be carried out once testing has been completed for all pts. The study is expected to conclude in 2019.
Clinical trial identification
NCT03078036, June 2020
Legal entity responsible for the study
T. Dalvi: Employee of MedImmune and AstraZeneca, stock ownership in AstraZeneca, Bristol-Myers Squibb, Roche, Achillion, Medivation, Inovio and Gilead. K.A. Gelmon: Consulting fees from Novartis, Pfizer, AstraZeneca, Merck, Genentech and Nanostring. R. Dent: Honoraria and consulting fees from AstraZeneca, Merck, Pfizer, Roche and Eisai, and travel and accommodation expenses from Pfizer. M. Pegram: Received consulting fees from Pfizer, Genentech and Amgen. Y. Tazir, A. Milner, J. Lewis: Employee of AstraZeneca. All other authors have declared no conflicts of interest.