Relationship between Complete Pathologic Response to Neoadjuvant Chemotherapy and Survival in Triple-Negative Breast Cancer.
OBJECTIVE
Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose of this study was to assess the relationship between increased pCR rate and trial-level survival benefit in triple-negative breast cancer (TNBC).


METHODS
We used bootstrap resampling from a neoadjuvant trial to simulate trials with different pCR rates. We used estimates from Adjuvant!Online to simulate trial populations with different baseline prognosis and estimated survival improvements associated with changes in pCR rate.


RESULTS
Assuming that survival is similar for patients with pCR regardless of treatment arm, a linear relationship exists between increasing pCR rate and increasing recurrence-free survival (RFS). The slope is equal to the difference in survival between those with pCR and residual disease, which in turn is influenced by (i) the baseline prognosis of the trial population, (ii) interactions between prognostic variables and pCR, and (iii) the efficacy of the postneoadjuvant therapies. For example, if the pCR rates are 30% and 60% (OR = 3.5) and the 10-year RFS of the control arm is 0.74, the trial would require 3,550 patients per arm, whereas if the RFS is 0.54, the trial would require only 425 patients per arm to detect significant survival benefit.


CONCLUSIONS
We provide a framework for understanding the relationship between pCR and overall survival benefit that can help inform the design of neoadjuvant trials aiming to demonstrate improved survival from a regimen that results in higher pCR rate.
Department of Internal Medicine, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut. christos.hatzis@yale.edu lajos.pusztai@yale.edu.
Christos
C
Hatzis
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
W Fraser
WF
Symmans
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ya
Y
Zhang
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Rebekah E
RE
Gould
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Stacy L
SL
Moulder
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kelly K
KK
Hunt
Department of Internal Medicine, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Maysa
M
Abu-Khalaf
Department of Internal Medicine, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Erin W
EW
Hofstatter
Department of Surgery, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Donald
D
Lannin
Department of Surgery, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut.
Anees B
AB
Chagpar
Department of Internal Medicine, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut. christos.hatzis@yale.edu lajos.pusztai@yale.edu.
Lajos
L
Pusztai
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology
D014408:Biomarkers, Tumor