56 yo postmenopausal F with no family hx, positive for BRCA 1, presents with R breast self palpated lump 2.3 cm, 1 LN in R axilla biopsy-proven.
You discuss neoadjuvant treatment with her.
a. What is the current standard of care?
b. What do you tell her about prognosis?
c. What new data has come out in the last few years that may indicate a future direction?
Answers:
a. Current SOC is an anthracycline-based NACT. The goal is to achieve path CR. For those who do not achieve path CR, adjuvant capecitabine based on CREATE-X is recommended.
Using data from KEYNOTE 522 data NEJM which I will discuss later, the path CR in the SOC arm which included anthracyclines was 51.2%. Very high grade 3 toxicity in both arms, approximately 73%.
Path CR in the pembro arm was 65% with grade 3 or higher of 78%. Remember this arm also got anthracycline.
The question now is can we avoid anthracycline altogether?
2 papers:
NEOSTOP trial showed path CR rates of 54% in anthracycline arm+ platinum and taxol ( standard 12 weeks platinum taxol then 4 cycles DDAC) and platinum taxotere alone for 6 cycles.
At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in anthracycline arm compared with anthracycline free, with the most notable differences in neutropenia (60% vs. 8%; P < 0.001) and febrile neutropenia (19% vs. 0%; P < 0.001). There was one treatment-related death (arm A) due to acute leukemia.
Below are the results of a meta-analysis that further supports this notion of anthracycline free chemotherapy regimens.
"For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding anthracyclines to the neoadjuvant chemotherapy regimen for TNBC is not apparent"
Based on this, my suspicion is that we will be moving to 12-16 weeks of carboplatin-taxane and keytruda followed by Keytruda maintenance if this can be proven in a phase III RCT.
Prognosis of patients who get NACT with or without path CR- refer to CREATE X trial results
What about low dose Xeloda maintenance?
Ans: applies to those who got adjuvant rather than NACT
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