Adjuvant oral agents in ER+ early breast cancer

 The OlympiA trial defined high-risk EBC as:

• HR-positive/HER2-negative: prior neoadjuvant CT and no pathologic complete response (pCR) plus a clinical and pathological stage plus estrogen receptor and nuclear grade (CPS + EG) score of 3 or more; prior adjuvant CT and at least 4 positive lymph nodes
• Triple-negative: prior neoadjuvant CT and no pCR; prior adjuvant CT and either node-positive or with a T2-T4 primary tumor at surgery

How to calculate CPS and EG score:

https://www3.mdanderson.org/app/medcalc/index.cfm?pagename=bcnt

• For patients with HR-positive/HER2-negative EBC who are eligible for both abemaciclib and olaparib, olaparib  is preferred because of proven OS benefit. This results in 1 year of adjuvant therapy with olaparib, which has a proven OS benefit, vs 2 (abemaciclib) or 3 (ribociclib) years of therapy with a CDK4/6 inhibitor and an unclear OS benefit at present. Do not give olaparib concurrently with a CDK4/6 inhibitor due to toxicity concerns.
• For patients with triple-negative EBC who are candidates for both olaparib and capecitabine and/or receiving the KEYNOTE-522 regimen of (neo)adjuvant pembrolizumab, we are typically selecting olaparib over capecitabine. Both drugs have demonstrated an OS benefit. For patients at very high risk of recurrence, healthcare professionals can consider sequencing both oral therapies—administering capecitabine for 6 to 8 cycles and then initiating olaparib; however, data supporting this strategy are lacking at this time. For both capecitabine and olaparib, we are administering these concurrently with pembrolizumab, for patients continuing immunotherapy in the adjuvant setting.

Reference: https://clinicaloptions.com/CE-CME/oncology/her2-negative-ebc-with-gbrca-pv/18910-34891/content

How do you counsel patients on the benefit of: 

1.  Adjuvant olaparib in BRCA mutated patients? HR for OS after 3 yr, 0.68, 90% versus 87% Olaparib versus placebo

2. Adjuvant abemaciclib? 5 yr IDFS HR 0.68, no OS benefit

3. Adjuvant  Ribociclib? Inclusion: In patients with node-negative disease, the risk of recurrence was defined as grade 2 plus evidence of high risk (Ki67 index > 20%; Oncotype DX Breast Recurrence Score > 26; or via genomic risk profiling). Other criteria for high-risk disease included node-positive disease or stage II or III disease.  3-year invasive disease–free survival rate was 90.7% with ribociclib vs 87.6% without it. OS data not mature. 25 % risk reduction in stage III, 30% risk reduction of IDFS in stage II.

4. Adjuvant Capecitabine in TNBC? OS improved by 5% at 5 years. 89% xeloda versus 83%