Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.
Authors: Foldi Julia , Kahn Adriana , Silber Andrea , Qing Tao , Reisenbichler Emily , Fischbach Neal A. , Persico Justin , Adelson Kerin B. , Katoch Anamika , Chagpar Anees B. , Park Tristen , Blanchard Adam , Blenman Kim , Rimm David L. , Pusztai Lajos 
Published: June 2022

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Background: The incidence of triple negative breast cancer (TNBC) is higher among Black or African American (AA) women, yet AA patients (pts) are underrepresented in clinical trials, exemplifying racial disparity in oncology. We conducted a phase I/II trial to assess the safety and efficacy of durvalumab concurrent with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) neoadjuvant therapy for stage I-III TNBC. The primary efficacy endpoint was pathologic complete response (pCR; ypT0/is,N0) rate. Given the unclear efficacy and safety of immunotherapy in AA pts with breast cancer, we extended our accrual to recruit AA pts, with the goal of evaluating the association between racial groups and PD-L1 expression, stromal tumor infiltrating lymphocytes (sTILs), toxicities, treatment response and survival. Methods: Our study population included 67 pts. PD-L1 immunohistochemistry results and sTIL counts were available on 59 and 60 pts, respectively. Chi-Squared test was used to evaluate associations between race and baseline characteristics. Cox proportional hazards model was used to assess association between AA race and overall survival (OS) and event free survival (EFS), adjusting for age, comorbidities and pCR status. Multivariate logistic regression analyses were used to evaluate the association between race and pCR, development of immune-related adverse events (irAEs) and breast cancer recurrence. Results: Twenty-one pts (31%) self-identified as AA. No significant associations between AA race and baseline body mass index (BMI; p=0.075), Charlson comorbidity index (p=0.32), tumor stage (p=0.40), grade (p=0.54), PD-L1 status (0.92) and sTIL count (p=0.57) were observed. pCR rates did not significantly differ between AA and non-AA pts: 9/21 (43%) AA vs. 22/48 (48%) non-AA (p=0.71). 3-yr OS was 87% in the non-AA versus 81% in the AA cohort (HR 1.72, 95% CI 0.481-6.136; p=0.405); 3 yr EFS were 78.3% and 71.4% in non-AA and AA pts respectively. (HR 1.451, 95% CI 0.524-4.017; p=0.474). Pts with pCR were more likely to remain event-free at 3 yrs, irrespective of race (HR 0.234, 95% CI 0.066-0.829; p=0.024). In multivariate logistic regression analyses, lack of pathologic response (OR for pCR 0.17, 95% CI 0.03-0.7; p=0.02) and node positive status (OR 4.13, 95% CI 1.05-19.88; p=0.05) were associated with recurrence. The incidence of irAEs was similar between AA and non-AA pts and no significant associations were found between irAEs and pathologic response. Conclusions: pCR rates after neoadjuvant immunotherapy and chemotherapy were similar in AA and non-AA pts. Stromal TILs, PD-L1 status, 3yr OS and EFS, and the frequency of irAEs were also similar. These results suggest that when patients receive identical treatment and are monitored closely, disparities in outcomes can be mitigated or abolished. Clinical trial information: NCT02489448.