One year of adjuvant therapy with the PARP inhibitor olaparib extended disease-free survival in patients with high-risk, early-stage, HER2-negative breast cancer with BRCA1/2 germline mutations, according to a prespecified interim analysis of the phase III OlympiA trial presented by Andrew Tutt, MB ChB, PhD, FMedSci, and colleagues at the 2021 ASCO Annual Meeting (Abstract LBA1).
At 24 months of follow-up, 85.9% of patients treated with adjuvant olaparib were alive and free of recurrent invasive cancer and new second cancer (ie, invasive disease–free survival) compared with 77.1% of placebo-treated patients. The estimated 3-year distant disease–free survival rate was 87.5% for olaparib vs 80.4% with placebo.
The OlympiA study results—the first reporting of the effect of a PARP inhibitor as adjuvant therapy on survival endpoints in breast cancer or any adjuvant setting—suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation–associated early breast cancer who have levels of risk requiring neoadjuvant or adjuvant chemotherapy.— Andrew Tutt, MB, ChB, PhD, FMedSci
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“The OlympiA study results—the first reporting of the effect of a PARP inhibitor as adjuvant therapy on survival endpoints in breast cancer or any adjuvant setting—suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation–associated early breast cancer who have levels of risk requiring neoadjuvant or adjuvant chemotherapy,” said lead author Dr. Tutt, 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.
“Patients who received adjuvant olaparib were more likely to be alive without cancer and avoid metastasis at 3 years of follow-up. Side effects were limited and manageable. These findings support adjuvant olaparib for 1 year after standard-of-care treatment in high-risk BRCA-mutated patients,” he stated. “Further, the results support germline testing of [patients with] breast cancer.”
BRCA mutations are associated with 5% to 10% of breast cancers. Newly diagnosed patients with breast cancer associated with these mutations can present with aggressive, high-risk disease. After completion of multimodality therapy (surgery, radiation, and chemotherapy), recurrence rates can be high, and additional novel, effective therapies are needed.
The double-blind phase III OlympiA trial included 1,836 patients with high-risk early breast cancer that was HER2-negative and BRCA1/2-positive, including triple-negative breast cancer and hormone receptor–positive breast cancer. Following treatment with surgery, radiation, and chemotherapy if needed, patients were randomly assigned to receive either 1 year of adjuvant olaparib or placebo.
“We used stringent criteria for invasive disease–free survival and distant disease–free survival, and at the planned interim analysis, these criteria were met for early reporting,” Dr. Tutt explained.
For the primary results, compared with placebo, adjuvant olaparib reduced the risk of invasive disease–free recurrence (ie, local recurrence, metastatic recurrence, other new cancers, and death due to any cause) by 42% compared with placebo (P < .0001).
“The Kaplan-Meier curves separate early, with an absolute difference of 8.8% between treatment arms at 3 years,” Dr. Tutt noted.
Compared to placebo, olaparib achieved a 43% reduction in distant disease–free survival (ie, risk of metastatic breast cancer, new cancer, or death due to any cause [P < .0001]). The difference between treatment arms was 7.1% at 3 years.
Overall survival is still immature, but fewer deaths occurred in the olaparib arm. “At this early timepoint [median of 2.5 years], given a stringent test for statistical superiority, there is no significant difference between treatment arms,” said Dr. Tutt.
The side effects were consistent with the safety profile of olaparib, and no new safety signals emerged during the trial. Olaparib did not increase the rate of serious adverse events, including hospitalization, leukemias, or other cancers. Grade 3 or worse adverse events in patients treated with olaparib included anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), fatigue (1.8%), and lymphocytopenia (1.2%).
“Grade 3 adverse events were infrequent,” added Dr. Tutt.
The study authors concluded, “Adjuvant olaparib following adjuvant or neoadjuvant chemotherapy significantly improved invasive disease–free survival and distant disease–free survival with acceptable toxicity in patients with germline BRCA-mutated and high-risk HER2-negative early breast cancer.”
“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,” commented ASCO President Lori J. Pierce, MD, FASTRO, FASCO.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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