Olaparib Adjuvant Therapy Indication in Breast Cancer
Olaparib (Lynparza) is indicated for adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCA) HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. [1] The NICE technology appraisal also recommends olaparib for the adjuvant treatment of HER2-negative high-risk early breast cancer treated with neoadjuvant or adjuvant chemotherapy in adults with germline BRCA1 or BRCA2 mutations. [2]
Patient Selection Criteria for Adjuvant Use
Adjuvant olaparib is indicated for patients with the following key features. [1]
- Deleterious or suspected deleterious germline BRCA mutation (gBRCA) (companion diagnostic selection applies). [1]
- HER2-negative early breast cancer. [1]
- High-risk early disease features as defined in the pivotal trial program eligibility. [1]
- Completion of definitive local treatment and neoadjuvant or adjuvant chemotherapy. [1]
High-Risk Early Breast Cancer Features (Trial-Based Definitions)
High-risk early breast cancer in the pivotal adjuvant study included the following definitions. [1]
- Patients receiving prior neoadjuvant chemotherapy: triple-negative breast cancer or hormone receptor–positive breast cancer with residual invasive cancer in the breast and/or resected lymph nodes at surgery (no pathologic complete response). [1]
- For hormone receptor–positive disease treated with neoadjuvant chemotherapy: a CPS score ≥3 based on pre-treatment clinical and post-treatment pathologic stage, estrogen receptor status, and histologic grade. [1]
- Patients receiving prior adjuvant chemotherapy: triple-negative disease with node-positive disease or node-negative disease with a primary tumor ≥2 cm. [1]
- For hormone receptor–positive, HER2-negative disease treated with prior adjuvant chemotherapy: ≥4 pathologically confirmed positive lymph nodes. [1]
Recommended Adjuvant Treatment Duration
Adjuvant therapy should be continued for a total of 1 year or until disease recurrence or unacceptable toxicity. [1] In the pivotal adjuvant trial experience, treatment was randomized to olaparib 300 mg orally twice daily versus placebo with a planned total duration of 1 year (or until recurrence or unacceptable toxicity). [1]
Key Efficacy Evidence Supporting the Indication
In OlympiA (gBRCA-mutated HER2-negative high-risk early breast cancer after neoadjuvant or adjuvant chemotherapy), olaparib improved invasive disease-free survival (IDFS) versus placebo. [1]
- IDFS hazard ratio: 0.58 (95% CI 0.46 to 0.74). [1]
- IDFS 3-year event-free rate: 86% with olaparib versus 77% with placebo. [1]
- Overall survival hazard ratio: 0.68 (95% CI 0.50 to 0.91). [1]
- Overall survival 3-year event-free rate: 93% with olaparib versus 89% with placebo. [1]
Monotherapy Versus Combination With Endocrine Therapy
Olaparib may be used alone or with endocrine therapy for the adjuvant setting as addressed by the NICE recommendation. [2] For patients receiving olaparib for hormone receptor–positive, HER2-negative breast cancer, continued concurrent endocrine therapy is recommended per current clinical practice guidelines. [1]
Common Pitfalls to Avoid
Adjuvant olaparib is restricted to HER2-negative, gBRCA-mutated high-risk early breast cancer that has received neoadjuvant or adjuvant chemotherapy. [1] Adjuvant olaparib duration should not exceed the indicated planned total of 1 year without reassessing for recurrence and toxicity. [1]
Treatment Goals in the Adjuvant Setting
The primary treatment goal of adjuvant olaparib is reduction in risk of invasive disease recurrence or death as reflected by IDFS improvement in OlympiA. [1] An additional treatment goal is improvement in overall survival as reflected by OS benefit in OlympiA. [1]