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Adjuvant Lynparza remains beneficial for patients with BRCA1/2 mutation–positive, HER2-negative high-risk breast cancer, study results have shown.
Patients with BRCA1/2 mutation-positive, HER2-negative high-risk breast cancer have continued to experience clinically meaningful results from treatment with adjuvant Lynparza (olaparib), study results have shown.
Six-year results from the third pre-specified analysis of the phase 3 OlympiA trial were reported at the reported at the 2024 San Antonio Breast Cancer Symposium.
The analysis occurred at a median follow-up of 6.1 years and 2.6 years since the previous analysis. The updated data for all first invasive disease-free survival (iDFS) events — the primary end point of the trial — demonstrated that distant (11.5% versus 16.3%), regional (1.2% versus 2.4%) and local recurrences (1.2% versus 1.3%) all continued to be less frequent in the Lynparza arm versus the placebo arm, Dr. Judy Garber reported at the symposium. This translated to a 9.4% absolute difference in the six-year iDFS rate favoring Lynparza versus placebo.
The iDFS benefit was consistent across all prespecified patient subgroups, including hormone receptor–positive patients and triple-negative patients.
Adjuvant: treatment that follows primary treatment.
Invasive disease-free survival: the time a patient lives without cancer.
Distant disease-free survival: the time a patient lives without the present of distant metastases, or sites where cancer has spread from its original location.
Overall survival: the time a patient lives regardless of disease status.
Neoadjuvant: treatment that precedes primary treatment.
“At this updated analysis, the magnitude of the benefit remains similar with more than 30% reduction in both groups,” said Garber, who is the Susan F. Smith Chair and chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School, both in Boston.
The absolute difference in the six-year distant disease-free survival (DDFS) rate also favored Lynparza at 7.8%. The DDFS benefit was consistent across all subgroups.
At the time of the updated analysis, there had been 107 (11.6%) deaths in the Lynparza arm and 143 (15.6%) deaths in the placebo arm. The primary cause of death in both arms was breast cancer recurrence (10.2%, Lynparza arm; 14%, placebo arm). The absolute difference in the six-year overall survival (OS) rate was 4.4% favoring Lynparza. As with iDFS and DDFS, the OS benefit was consistent across all subgroups.
“These data continue to support adjuvant [Lynparza] as standard of care for patients with BRCA+ high-risk HER2-negative primary breast cancer and therefore highlight the importance of germline BRCA testing for treatment planning,” said Garber.
The safety population included 911 patients in the Lynparza arm and 904 patients in the placebo arm. Adverse events (AEs, side effects) of special interest continued to be higher in the placebo arm. AEs of special interest occurring at any time were reported in 6.3% of the Lynparza arm versus 9.3% in the placebo arm.
There were fewer second primary malignancies in the Lynparza group at 4.9% versus 7.5%. “Of note, with further follow-up the incidence of MDS/AML events, in particular, remains low with four in the [Lynparza] arm and six in the placebo arm,” said Garber.
The multicenter OlympiA trial enrolled 1,836 patients with HER2-negative breast cancer harboring a germline BRCA1/2 mutation. Patients were randomized evenly to receive 300 milligrams (mg) of oral Lynparza twice daily for a year (921 patients) or placebo (915 patients). Additionally, patients had to have been treated for stage 2 or 3 breast cancer, and have completed surgery and chemotherapy, with or without radiotherapy. Inclusion criteria also required that patients have a high risk of disease recurrence. Prior treatment with a PARP inhibitor was not allowed.
Patient characteristics were well balanced between the study arms, with a median age of about 43 years. About 70% of patients in each cohort had a BRCA1 mutation, with about 30% having a BRCA2 mutation. Around 60% of patients in each arm were premenopausal and nearly 75% had received mastectomy. Approximately 80% of patients in each arm were triple-negative. About half of the patients in each cohort received adjuvant chemotherapy and about half received neoadjuvant chemotherapy. About 90% of the hormone receptor–positive patients in the study groups received concurrent endocrine therapy.
Significant benefits for IDFS and DDFS with Lynparza had been previously demonstrated in the first interim analysis of the OlympiA trial, as well as a significant OS benefit in the second analysis.
Based on the initial data from the OlympiA trial, the FDA previously approved Lynparza for the adjuvant treatment of patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have previously received chemotherapy either before or after surgery.
In her concluding remarks, Garber noted that blinded follow-up for the final planned analysis of the OlympiA trial is continuing until June 2029.
Reference:
OlympiA- Phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients w/ germline BRCA1/BRCA2 pathogenic variants & high risk HER2-negative primary breast cancer; longer term follow.-up, presented by Dr. Judy Garber at San Antonio Breast Cancer Conference; Dec. 10 to 13, 2024; San Antonio, Texas.
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