Adjuvant PARP Inhibitors for Patients with Germline BRCA1 and BRCA2 Variants

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

Patients with triple-negative breast cancer (TNBC) had axillary node-positive (≥pN1, any tumor size) disease OR axillary node-negative disease with an invasive primary tumor larger than 2 cm (pN0, ≥pT2).

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

At least four pathologically confirmed positive lymph nodes were required for ER- and/or PR-positive/HER2-negative patients.

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

Patients with TNBC had residual invasive cancer in the breast and/or resected lymph nodes (i.e., no pCR).

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

ER- and/or PR-positive/HER2-negative patients had residual invasive cancer in the breast and/or resected lymph nodes (i.e., no pCR) AND a CPS+EG (Clinical stage/Pathological Stage + ER status/nuclear Grade) score of 3 or higher.[101]

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

At the time of the first (and only) planned interim analysis, when 284 events (i.e., invasive disease or death) had occurred, the HR for IDFS strongly favored the olaparib arm, and the prespecified stopping boundary for significance was exceeded (3-year IDFS rate, 85.9% vs 77.1%; HR, 0.58; 99.5% CI, 0.41–0.82; P < .001).[100][Level of evidence B1]

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

Distant DFS was also statistically significantly improved for patients who received olaparib (HR, 0.57; 99.5% CI, 0.39–0.83; P < .001).

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

A difference in OS was also observed (HR, 0.68; 99% CI, 0.44–1.05; P = .02), but it did not meet the prespecified level of significance when corrected for multiple testing (P < .01).

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

Grade 3 or higher adverse events that occurred in more than 1% of patients on the olaparib arm included anemia (8.7%), decreased neutrophil count (4.8%), decreased white cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). No adverse events of grade 3 or higher occurred in more than 1% of the patients on the placebo arm.

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1]

Patient-reported outcomes were assessed among the 1,538 patients who completed both a baseline questionnaire and at least one subsequent questionnaire.[102]

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1] › Patient-reported outcomes were assessed among the 1,538 patients who completed both a baseline questionnaire and at least one subsequent questionnaire.[102]

Patients who received olaparib experienced statistically significant greater fatigue than patients who received placebo, but the differences did not meet the criteria for clinical significance. The fatigue resolved over time after cessation of therapy.

The OlympiA trial (NCT02032823) randomly assigned 1,836 patients with HER2-negative breast cancer and germline BRCA1 or BRCA2 pathogenic variants to receive either 1 year of adjuvant olaparib (300 mg twice daily) or placebo. All women completed surgery and adjuvant or neoadjuvant chemotherapy or radiation therapy. Patients were considered at higher risk of recurrence on the basis of tumor size, node involvement, or the presence of residual cancer after neoadjuvant therapy.[100]Eligibility criteria for patients who underwent initial surgery and received adjuvant chemotherapy Eligibility criteria for patients who underwent neoadjuvant chemotherapy followed by surgeryThe primary study end point was invasive disease-free survival (IDFS).[100][Level of evidence B1] › Patient-reported outcomes were assessed among the 1,538 patients who completed both a baseline questionnaire and at least one subsequent questionnaire.[102]

Patients who received olaparib had small but statistically and clinically significant increases in nausea, vomiting, and appetite loss scores during treatment.[102][Level of evidence A3]