Abstract P1-15-05: Is absolute lymphocyte count associated with platinum-sensitivity? A phase II single arm study evaluating the efficacy of neoadjuvant carboplatin and docetaxel in triple negative breast cancer
Authors: Chen I , Guo F , Summa T , Luo J , Ellis MJ , Ma CX , Weilbaecher KN , Naughton MJ , Suresh R , Peterson LL , Cherian MA , Bose R , Frith AE , Hernandez-Aya LF , Gillanders WE , Ademuyiwa FO 
Published: May 2019

Abstract
Background: Platinum-based chemotherapy is still considered investigational for the treatment of sporadic triple negative breast cancer (TNBC). Since patients with TNBC have a high rate of chemotherapy resistance, it is critical to identify platinum-sensitive individuals prior to initiating therapy. Higher absolute lymphocyte count (ALC) is associated with improved clinical response to anthracycline-based chemotherapy, the current standard of care in TNBC. We report the initial results of a phase II single arm study evaluating the efficacy of neoadjuvant carboplatin and docetaxel in TNBC. We also report results of an exploratory analysis assessing whether ALC can be used to predict pathologic complete response (pCR) after treatment with platinum-based chemotherapy.
Patients and Methods: 78 patients with clinical stage II or III TNBC have been enrolled in this ongoing study evaluating the efficacy of neoadjuvant carboplatin and docetaxel (NCT201404107). Patients received docetaxel 75 mg/m2 and carboplatin AUC 6 every three weeks for a total of 6 cycles. Blood samples were collected prior to each cycle, and a posttreatment sample was collected &gt; 3 weeks after completing cycle 6. pCR was defined as no residual invasive disease in the breast, with or without ductal carcinoma in situ, and no tumor deposits in sampled lymph nodes. Baseline characteristics of patients were summarized with descriptive statistics. Univariate and multivariate logistic regression analyses were used to identify factors associated with pCR.
Results: Out of the 78 enrolled patients, 60 have completed all 6 treatment cycles and surgery. The preliminary pCR rate is 46.7%. Age, race, clinical stage, and tumor grade determined at time of diagnosis were not significantly different between pCR patients and non-pCR patients. In univariate analyses, patients with higher ALCs at the posttreatment time point were more likely to have pCR than those who had lower ALCs (OR 5.5, 95% CI 1.5-20.7, p=0.011). Additionally, patients who had higher minimum ALCs were also more likely to have pCR (OR 9.1, 95% CI 1.5-54.9, p=0.016). Baseline ALC values were not associated with pCR. The associations of posttreatment and minimum ALCs to pCR remained statistically significant even after controlling for age and clinical stage at time of diagnosis (posttreatment ALC OR 7.6, 95% CI 1.7-34.8, p=0.009; minimum ALC OR 9.0, 95% CI 1.5-55.2, p=0.018).
Conclusion: The pCR rate of our cohort is similar to that of other trials evaluating neoadjuvant platinum-based chemotherapy in TNBC. Baseline ALC did not predict which patients would achieve pCR. However, the associations of posttreatment and minimum ALCs with pCR indicate patients who are able to maintain a robust population of circulating lymphocytes throughout treatment with platinum-based chemotherapy are more likely to respond favorably. The link between patient immunity and platinum-based chemotherapy suggests addition of immunotherapy agents to neoadjuvant chemotherapy may improve patient outcomes.
Citation Format: Chen I, Guo F, Summa T, Luo J, Ellis MJ, Ma CX, Weilbaecher KN, Naughton MJ, Suresh R, Peterson LL, Cherian MA, Bose R, Frith AE, Hernandez-Aya LF, Gillanders WE, Ademuyiwa FO. Is absolute lymphocyte count associated with platinum-sensitivity? A phase II single arm study evaluating the efficacy of neoadjuvant carboplatin and docetaxel in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-05.