ypT0 ypN0 Research Articles

Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer

Trastuzumab emtansine (T-DM1) is presently approved for treatment of advanced breast cancer and after incomplete response to neoadjuvant therapy, but the potential of T-DM1 as monotherapy is so far unknown. To assess pathologic complete response (pCR) to standard neoadjuvant therapy of combination docetaxel, trastuzumab, and pertuzumab (DTP) vs T-DM1 monotherapy in patients with ERBB2 (formerly HER2)-positive breast cancer. This randomized phase 2 trial, conducted at 9 sites in Sweden, enrolled 202 patients between December 1, 2014, and October 31, 2018. Participants were 18 years or older, with ERBB2-positive tumors larger than 20 mm and/or verified lymph node metastases. Analysis was performed on an intention-to-treat basis. Patients were randomized to receive 6 cycles of DTP (standard group) or T-DM1 (investigational group). Crossover was recommended at lack of response or occurrence of intolerable toxic effects. Assessment with fluorine 18-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography combined with computed tomography (PET-CT) was performed at baseline and after 2 and 6 treatment cycles. Pathologic complete response, defined as ypT0 or Tis ypN0. Secondary end points were clinical and radiologic objective response; event-free survival, invasive disease-free survival, distant disease-free survival, and overall survival; safety; health-related quality of life (HRQoL); functional and biological tumor characteristics; and frequency of breast-conserving surgery. Overall, 202 patients were randomized; 197 (99 women in the standard group [median age, 51 years (range, 26-73 years)] and 98 women in the investigational group [median age, 53 years (range, 28-74 years)]) were evaluable for the primary end point. Pathologic complete response was achieved in 45 patients in the standard group (45.5%; 95% CI 35.4%-55.8%) and 43 patients in the investigational group (43.9%; 95% CI 33.9%-54.3%). The difference was not statistically significant (P = .82). In a subgroup analysis, the pCR rate was higher in hormone receptor-negative tumors than in hormone receptor-positive tumors in both treatment groups (45 of 72 [62.5%] vs 45 of 125 [36.0%]). Three patients in the T-DM1 group experienced progression during therapy. In an exploratory analysis, tumor-infiltrating lymphocytes at 10% or more (median) estimated pCR significantly (odds ratio, 2.76; 95% CI, 1.42-5.36; P = .003). Response evaluation with 18F-FDG PET-CT revealed a relative decrease of maximum standardized uptake value by equal to or greater than 68.7% (median) was associated with pCR (odds ratio, 6.74, 95% CI, 2.75-16.51; P < .001). In this study, treatment with standard neoadjuvant combination DTP was equal to T-DM1. ClinicalTrials.gov Identifier: NCT02568839; EudraCT number: 2014-000808-10.

Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC).

506 Background: The GeparNuevo trial investigated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor (CPI), to standard neoadjuvant chemotherapy (NACT) in patients with early TNBC. Durvalumab increased the pathological complete response (pCR) rate particularly in patients treated with durvalumab alone before start of chemotherapy (Loibl et al. Ann Oncol 2019). Methods: GeparNuevo randomized patients with cT1b-cT4a-d tumors and centrally confirmed TNBC to durvalumab (D) 1.5 g i.v. or placebo every 4 weeks. D/placebo monotherapy (0.75 g i.v.) was given for the first 2 weeks (window phase), followed by D/placebo plus nab-paclitaxel 125 mg/m² weekly for 12 weeks, followed by D/placebo plus epirubicin/cyclophosphamide (EC) q2 weeks for 4 cycles. Randomization was stratified by stromal tumor infiltrating lymphocytes (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). The primary objective was pCR (ypT0 ypN0). Secondary time-to-event endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 174 patients were enrolled between June 2016 and September 2017. The pCR rate with durvalumab was 53.4% versus placebo 44.2% (OR 1.45, 95% CI 0.80–2.63, unadjusted Wald p = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR 2.22, 95% CI 1.06–4.64, p = 0.035; interaction p = 0.048). After a median follow-up of 42.2 months, 34 events occurred in 174 patients. 3-year iDFS in pCR vs non pCR was 92.0% vs 71.9% (log-rank p = 0.002). 3-year iDFS was 84.9% with durvalumab vs 76.9% with placebo (HR 0.54, 95%CI 0.27-1.09, stratified log-rank p = 0.0559); 3-year DDFS 91.4% vs 79.5% (HR 0.37, 95%CI 0.15-0.87, p = 0.0148); 3-year OS 95.1% vs 83.1% (HR 0.26, 95%CI 0.09-0.79, p = 0.0076). No difference was seen in iDFS, DDFS and OS between the window and no window cohort. Conclusions: Durvalumab added to neoadjuvant chemotherapy in TNBC significantly improved long-term outcome despite a small pCR increase and no continuation after surgery. It needs to be questioned whether adjuvant therapy with CPI is needed at all. Clinical trial information: NCT02685059.

Do hospital type or caseload make a difference in chemotherapy treatment patterns for early breast cancer? Results from 104 German institutions, 2008–2017

BackgroundOver the past decade, chemotherapy has been used more selectively in early breast cancer (EBC) due to better risk stratification. Neoadjuvant chemotherapy (NACT) has evolved to the primary treatment option. The type and size of hospitals is known to have a substantial influence on the kinds of treatment they provide, and therefore on patient outcomes (e.g. rates for pathological complete response, pCR), but it is not yet known how this has affected delivery of chemotherapy for EBC in Germany. MethodsThis study analyzed chemotherapy use and pCR rates after NACT for EBC patients treated at 104 German institutions 2008–2017. Institutions were separated into associated hospital type (university hospital; teaching hospital; community hospital) and annual caseload (≤100; 101–250; >250 cases/year). ResultsOverall, 124,084 patients were included, of whom 11.6% were treated at university hospitals, 63.1% at teaching hospitals, and 25.3% at community hospitals. In total, 46,274 (37.3%) received chemotherapy, of whom 44,765 had information available about systemic treatment and surgery. From 2008 to 2017, chemotherapy use declined from 48.3% to 36.4% for university hospitals, from 40.7% to 30.3% for teaching hospitals, and from 42.4% to 33.7% for community hospitals. Furthermore, the proportion of NACT increased the most in university hospitals (from 32.0% to 68.1%); whereas, the rate of pCR (defined as ypT0 ypN0) increased irrespective of institutional type. Analyses regarding annual caseload did not show any differences. ConclusionsThe results from this large, nationwide cohort reflect a more selective use of chemotherapy in Germany, irrespective of institutional type or case load.

Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study)

BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies.MethodsWe conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype.ResultsWe analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered.ConclusionsNab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774

Abstract PS3-10: Monitoring neoadjuvant chemotherapy using diffuse optical tomography breast imaging system

Abstract Background: Optical based imaging modalities have shown promise for monitoring tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. In this study, we evaluate whether changes in deoxy-hemoglobin concentration values acquired by a Diffuse Optical Tomography Breast Imaging System (DOTBIS) over different time points are associated with tumor response. Methods: This is a retrospective evaluation of 55 stage II-III BC patients in the neoadjuvant setting who received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4. The patients were enrolled in this cohort study between 2011 and 2019, and DOTBIS images were acquired from the patient whole breast volume at 6 different time points: at baseline (TP0); two weeks after the first taxane infusion (TP1); after four infusions of taxane (TP2); at the end of the taxane regimen and before starting AC cycle (TP3); after two AC infusions (TP4); and at the end of NAC and before surgery (TP5). ctHHb tumor concentration was measured using low-intensity near-infrared light and normalized by the non-tumor region ctHHb mean value (ctHHbN). In order to evaluate whether pCR status, menopausal status, and molecular subtype classification influence the change of ctHHbN over time, we designed a multilevel mixed-effect statistical model. pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Results: 20 patients had pCR and 35 were classified as non-pCR. The estimate average ctHHbN for pCR tumors at baseline was 4.02. There was a significant reduction in ctHHbN levels for pCR group at TP1 (-1.31, p = .0001) and TP2 (-1.36, p = .0416). Changes in ctHHbN levels compared to baseline (TP0) values were statistically significant different between pCR and non-pCR at all time points except at the end of the taxane cycle (TP3), Table 1. No significant changes over time were identified between molecular subtypes groups, or between pre- and post-menopausal status. Conclusions: Our study adds to the body of evidence reported for diffuse optical imaging methods applied to breast cancer treatment response. These results show that DOTBIS measured features, such as ctHHbN, change in accordance with pCR status after 2 weeks under NAC, and there are differences in time evolution between the pCR groups. Reduction in ctHHbN levels represents the chemotherapeutic- induced changes in the tumor microvasculature: lower ctHHbN values associate with the reduction in tumor cell proliferation, and consequently in oxygen consumption. Future studies are warranted to evaluate whether early response prediction might determine if earlier treatment changes alter patient outcome. Table 1 - Changes in ctHHbN levels compared to baseline (TP0) values between pCR and non-pCR at all imaging time points. Bold values indicate statistical significance at p &amp;lt;.05 level.Time PointMean Difference ± Std. Errorp-valueTP11.92 ± 0.400.0000TP22.04 ± 0.820.0145TP30.83 ± 1.030.4198TP42.71 ± 0.870.0021TP52.63 ± 0.900.0037 Citation Format: Mirella L Altoe, Kevin Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Monitoring neoadjuvant chemotherapy using diffuse optical tomography breast imaging system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-10.

Abstract PS13-08: Predictors and long-term outcome of pathologic complete response in patients receiving neoadjuvant chemotherapy for breast cancer - an NCDB analysis

Abstract Background: Among women with high-risk early stage breast cancer, neoadjuvant chemotherapy (NCT) is increasingly utilized. The Collaborative Trials in Neoadjuvant Breast Cancer working group studied 13,000 patients from 12 large trials involving NCT and concluded that pathologic complete response (pCR) resulted in significantly better outcomes with respect to both disease recurrence and mortality. This National Cancer Database (NCDB) study aims to gather patient and tumor characteristics to further identify prognosticators of pCR, and determine which subgroups achieving pCR have the greatest survival benefit. Methods: Retrospective analysis using NCDB data from 2004-2015 identified 46,836 women ≥18 years with stage I to III breast cancer who received NCT. Achievement of pCR was defined as ypT0 ypN0 or ypT0/is ypN0. Tumor and patient characteristics were evaluated, and multivariate logistic regression was used to calculate odds ratio (OR) of pCR. Kaplan-Meier curves were constructed for calculation of overall survival (OS) at 5 years. Hazard ratios (HR) were estimated from Cox models. Propensity score weighting was used to adjust for confounding effects of various factors on survival via Cox regression. Results: Patients were more likely to achieve pCR with ductal vs. lobular histology (OR 1.62 [95% CI 1.414-1.872]), grade 3 vs. 1 (OR 1.606 [95% CI 1.394-1.849]), stage 3 vs. 1 (OR 1.76 [95% CI 1.623-1.908]), ER+PR- vs. ER+PR+ (OR 2.004 [95% CI 1.855-2.165]), ER-PR- vs. ER+PR+ (OR 2.572 [95% CI 2.425-2.729]), age &amp;lt;60 (OR 1.43 [95% CI 1.32-1.55]), Charlson-Deyo combined comorbidity (CDCC) score of 0 vs. 2 (OR 1.27 [95% CI 1.04-1.54]), and private insurance vs. uninsured (OR 1.24 [95% CI 1.09-1.41]). HR for death adjusted by propensity score in patients attaining pCR vs. non-pCR was 0.346 (95% CI 0.325-0.368) for the overall cohort, 0.591 (95% CI 0.513-0.681) for ER+PR+ patients, 0.373 (95% CI 0.315-0.442) in the ER+PR- group, and 0.307 (95% CI 0.284-0.332) for ER-PR- patients. Achieving pCR conferred better OS in all subgroups with higher magnitude in hormone negative patients (table 1). Conclusions: This study not only highlights factors associated with achieving pCR after neoadjuvant chemotherapy for breast cancer, but also demonstrates that attaining pCR reduces the risk of death by 65.4% in all patients regardless of receptor subtype. Furthermore, the survival curve increasingly separates with time. Our study reveals an intriguing observation that ER+PR+ patients who attain pCR have 40.9% decreased mortality compared to non-pCR. Limitations of this analysis include the lack of HER2 status and that conclusions are made from non-population based observational data. Despite utilization of propensity score weighting, there may have been confounders that were not adjusted for by the multivariate model. Future analysis is needed to identify HER2 status, as HER2-positive patients may have contributed to the OS benefit in the subgroups. Nonetheless, these data are among the first to suggest that hormone-positive patients derive long-term survival benefit from achievement of pCR, albeit to a lesser extent than hormone-negative subtypes. Table 1. 5-year survival estimates from Kaplan-Meier analysispCRNon-pCRSurvival differencep (95% CI)All patients0.88500.73840.14657&amp;lt;0.0001 (0.1364-0.1567)ER+PR+0.90300.81170.09121&amp;lt;0.0001 (0.0744-0.1079)ER+PR-0.89620.70740.18879&amp;lt;0.0001 (0.1609-0.2166)ER-PR+0.88070.63880.24198&amp;lt;0.0001 (0.1719-0.3120)ER-PR-0.87570.64660.22913&amp;lt;0.0001 (0.2131-0.2451) Citation Format: Lauren Mikesell Panebianco, Prashanth Ashok Kumar, Shreya Sinha, Dongliang Wang, Danning Huang, Abirami Sivapiragasam. Predictors and long-term outcome of pathologic complete response in patients receiving neoadjuvant chemotherapy for breast cancer - an NCDB analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-08.

Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis

BackgroundTo compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer.MethodsWe systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019.ResultsThe primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27–1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17–1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07–2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54–5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26–2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57–0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11–0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37–3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51–6.41, P < 0.001) neuropathy.ConclusionNab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis. MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis. ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06). ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.

Time trends of neoadjuvant chemotherapy for early breast cancer

Neoadjuvant chemotherapy (NACT) in early breast cancer (EBC) enables in vivo sensitivity testing and less radical surgery as compared to primary surgery and adjuvant chemotherapy (ACT). The aim of our study is to illustrate trends of systemic treatment of EBC. The study analyzed chemotherapy usage and time trends for patients with EBC treated at 104 German breast units between January 2008 and December 2017. The data were obtained through a quality-controlled benchmarking process. Altogether, 124 084 patients were included, of whom 46 279 (37.3%) received chemotherapy. For 44 765 of these cases, detailed information on systemic treatment and surgery were available. Overall use of chemotherapy declined from 42.0% in 2008 to 32.0% in 2017. During that same time, the proportion of NACT increased from 20.0% to 57.7%, irrespective of tumor subtype. The pathological complete response (pCR) rate (defined as ypT0 ypN0) at surgery after NACT increased from 15.0% to 34.2%. The results from this large cohort from the clinical routine reflect the refined indications for chemotherapy in EBC.

A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL.

TPS604 Background: Patients (pts) diagnosed with primary estrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2−) breast cancer (BC) of high grade and/or low ER expression are at increased risk of relapse, despite current standard of care (SoC). Promising data assessing programmed death-1 (PD-1) inhibition coupled with neoadjuvant chemotherapy for pts with high-risk ER+, HER2− BC noted improved pathologic complete response (pCR), which is identified as a valid surrogate endpoint for long-term clinical outcomes. Methods: CheckMate 7FL (NCT04109066) is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 study evaluating nivolumab (NIVO) vs placebo (PBO) in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy (ET) in pts with high-risk, ER+, HER2− primary BC. Eligible pts are male or female, aged ≥18 years with newly diagnosed grade 2 with ER expression of 1–9%, or grade 3, T1c-2, cN1-2 (tumor size ≥2 cm) or T3-T4, cN0-cN2 ER+, HER2− BC. Pts eligible for neoadjuvant chemotherapy and surgery, with adequate organ function, ECOG PS of 0 or 1, and tissue available for biomarker assessments will be enrolled. Approximately 1200 pts will be randomized 1:1 to NIVO or PBO, stratified by programmed death ligand 1 (PD-L1) expression, tumor grade (2 or 3), axillary nodal status (+ or −), and anthracycline + cyclophosphamide schedule (Q3W or Q2W). In the neoadjuvant phase, pts will receive NIVO 360 mg Q3W or PBO + paclitaxel 80 mg/m2 QW for four 3-week cycles, followed by NIVO 360 mg Q3W (or 240 mg Q2W) or matching PBO in combination with either doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 Q3W or Q2W for 4 cycles. Pts will undergo surgery after completion of the neoadjuvant phase. Following surgery, pts will enter the adjuvant phase and receive NIVO 480 mg Q4W or PBO for 7 cycles + investigator’s choice of ET per local SoC. Primary endpoints are pCR (ypT0/is, ypN0) and event-free survival. Secondary endpoints include overall survival, disease-free survival, distant-metastasis-free survival, safety, pCR (ypT0 ypN0 and ypT0/is) rates, overall response rates, residual cancer burden, and quality of life. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04109066 .

Pathological outcomes of HER2-positive early breast cancer patients treated with neoadjuvant trastuzumab or dual anti-HER2 therapy and carboplatin with docetaxel: A Maria Sklodowska-Curie National Research Institute of Oncology experience.

e12655 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer predicts the risk of recurrence and increasingly may indicate the need for additional therapy postoperatively. Methods: A retrospective analysis was performed in two cohorts of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) or with docetaxel, carboplatin and dual blockade (TCH-P) in the neoadjuvant setting in patients with early breast cancer (tumor size &lt; 50 mm and &gt; 10 mm and cN0 or cN1) in our Clinic, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. The pCR was defined as ypT0 ypN0. Results: Patient in cohort A (n = 58) received TCH x 6 cycles and in cohort B (n = 25) TCH-P x 6 cycles. Median age was 51 (range 23 to 76 years) in cohort A and 46 (range: 30-68) in cohort B. In cohort A 37 (64%) of pts was HR-positive, in cohort B only 9 (36%) pts . The most common adverse events in both groups were neutropenia, diarrhea, chemotherapy induced polyneuropathy and febrile neutropenia. There are no significant differences in the frequency of adverse events in two cohorts. There was no symptomatic heart failure, but 6 pts (10%) in cohort A and 5 pts (16%) in cohort B had &gt; 10% asymptomatic decrease in LVEF. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2pos/HRneg pts: 66% (n = 14) in cohort A, and 87% (n = 14) in cohort B. In group HER2pos/HRpos pts, the pCR rate was 48% (n = 18) vs 55% (n = 5) respectively. Conclusions: In HER2positive early breast cancer, a dual blockade (trastuzumab and pertuzumab) together with carboplatin and docetaxel neoadjuvant chemotherapy achieved higher rates of pCR ( 76%) compared with pts treated with trastuzumab, carboplatin and docetaxel (56%). However, a much higher percentage of pCR was observed in the group of patients with non-luminal cancers, who received a double blockade (87% vs 66%).

Clinical parameters predictive for sphincter-preserving surgery and prognostic outcome in patients with locally advanced low rectal cancer

BackgroundAlthough controversial, there are data suggesting that clinical parameters can predict the probability of sphincter preserving procedures in rectal cancer. The purpose of this study was to investigate the association between clinical parameters and the sphincter-preserving surgery rate in patients who had undergone neoadjuvant combination therapy for advanced low rectal cancer.MethodsIn this single center study, the charts of 540 patients with locally advanced rectal cancer who had been treated with induction chemotherapy-and/or neoadjuvant concomitant radiochemotherapy (nRCT) over an 11-year period were reviewed in order to identify patients with rectal cancer ≤6 cm from the anal verge, who had received the prescribed nRCT only. Univariate and multivariate analyses were used to identify pretreatment patient- and tumor associated parameters correlating with sphincter preservation. Survival rates were calculated using Kaplan-Meier analyses.ResultsTwo hundred eighty of the 540 patients met the selection criteria. Of the 280 patients included in the study, 158 (56.4%) underwent sphincter-preserving surgery. One hundred sixty-four of 280 patients (58.6%) had a downsizing of the primary tumor (ypT < cT) and 39 (23.8%) of these showed a complete histopathological response (ypT0 ypN0). In univariate analysis, age prior to treatment, Karnofsky performance status, clinical T-size, relative lymphocyte value, CRP value, and interval between nRCT and surgery, were significantly associated with sphincter-preserving surgery. In multivariate analysis, age (hazard ratio (HR) = 1.05, CI95%: 1.02–1.09, p = 0.003), relative lymphocyte value (HR = 0.94, CI95%: 0.89–0.99, p = 0.029), and interval between nRCT and surgery (HR = 2.39, CI95%: 1.17–4.88, p = 0.016) remained as independent predictive parameters.ConclusionsThese clinical parameters can be considered in the prognostication of sphincter-preserving surgery in case of low rectal adenocarcinoma. More future research is required in this area.

Abstract P2-16-13: Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01)

Abstract [Background] Nanoparticle albumin-bound paclitaxel (Nab-PTX) is a novel taxane formulation that was developed to avoid Cremophor/ethanol associated toxicities such as peripheral neuropathy and hypersensitive reactions. Since Taxol plays an important role in breast cancer therapy, Nab-PTX is considered safe and effective for metastatic breast cancer (MBC). According to these reports, a regimen including Nab-PTX in a neoadjuvant setting may induce preferable results. Several recent reports using a combination of Nab-PTX and anthracycline in neoadjuvant chemotherapy (NAC) have been published. In Japan, at least 34 small phase II studies using a Nab-PTX regimen have been registered with the University hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR). We believe that integration of these data is important to evaluate the power of Nab-PTX, so we conducted a meta-analysis based on individual patient data (IPD). [Materials and Methods] This study is a collaborative meta-analysis of single arm trials using IPD to summarize the published and unpublished evidence of Nab-PTX-containing regimen efficacy. The main objective was to assess the rate of pathological complete response (pCR). Definitions of pCR were (1) ypT0 ypN0, (2) ypT0/is ypN0, and (3) ypT0/is ypNX. The secondary objectives were adverse events (AEs) (≥G3) and dose of administered Nab-PTX (mg/m2). First, we found 34 phase II studies registered from Feb 2011 to Jun 2016 using an electron search of UMIN-CTR. Second, we contacted each principal investigator (PI) to ask if they would participate in this study by providing individual data. Inclusion criteria were as follows: (1) Clinical trial(s) started after July 2010, (2) Principal investigator(s) in each trial agreed with study participation, (3) Nab-PTX-containing regimen was used for neoadjuvant chemotherapy in naive operable breast cancer patients, (4) Registered in UMIN with ethical review, (5) Clinical trials with more than 10 patients, (6) Completed clinical trials only were included (unpublished data are available), and (7) Each researcher was authorized by the research ethics committee to submit the data. pCR rates in all cases/each subtype were calculated with a 95% confidence interval (CI). The proportion of AEs and total Nab-PTX dose were also calculated. [Results] Among 34 studies, 16 studies (4 published, 12 unpublished) included 758 patients. Among these 16 studies, 5 (2 metastatic, 3 no treatment) were excluded for all analyses (n=753). After excluding 8 (3 declined surgery, 1 hospital transfer, 4 unknown), a total of 745 (including 2 PD, 1 death) were analyzed for the primary analysis. All HER2-positive cases were treated by combining Nab-PTX and trastuzumab. Crude overall percentages of pCR (ypT0ypN0, ypT0/isypN0, and ypT0/isypNX) were 18.1%, 26.0%, and 28.6%, respectively. In detail, 6.7%, 10.2%, and 13.4% for Luminal type (n=343), 26.3%, 31.5%, and 32.3% for triple negative (TNBC, n=232), 40.5%, 63.5%, and 68.9% for HER2-rich (n=74), 21.9%, 40.6%, and 42.7% for Luminal/HER2 type (n=96), respectively. AEs (≥G3) were observed as follows: 41.5% neutropenia, 32.3% leukopenia, 10.6% febrile neutropenia, 10.6% peripheral sensory neuropathy, 2.5% peripheral motor neuropathy, 6.4% myalgia, 5.5% arthralgia, 6.1% hepatobiliary disorders, 4.5% vomiting, 0.7%, cardiac disorders, and 0.9% infusion reaction. Only one patient died during FEC followed by Nab-PTX. [Conclusion] NAC regimen containing Nab-PTX was safe, and the efficacy was equal to or greater than regimens containing other taxanes. The combination Nab-PTX and trastuzumab is particularly useful and powerful against the HER2-positive subtype. However, the Nab-PTX-containing regimen is not as powerful against TNBC in a neoadjuvant setting. Citation Format: Manabu Futamura, Mari Oba, Norikazu Masuda, Hiroko Bando, Yutaka Yamamoto, Takanori Kin, Toshiaki Saeki, Takeshi Nagashima, Takashi Kuwayama, Uhi Toh, Akira Hirano, Masafumi Inokuchi, Kazuhiko Yamagami, Yutaka Mizuno, Yasuyuki Kojima, Takahiro Nakayama, Hiroyuki Yasojima, Morihito Okada, Shinji Ohno. Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-13.

Abstract OT2-04-03: Nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL

Abstract Background: Estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC) includes a group of heterogeneous tumors, spanning from biologically indolent, ER signaling-driven to aggressive, endocrine-resistant tumors. Patients (pts) diagnosed with ER+, HER2− BC of high grade and/or low ER expression are at increased risk of relapse, despite current standard of care (SoC): chemotherapy and endocrine treatment (ET) in the neo- and adjuvant settings, respectively. New treatment options to increase cure rates are needed. Increased understanding of ER+, HER2− BC immune biology show an enrichment of cases with tumor cell recognition by the immune system and immune suppression mediated via programmed-death-1 (PD-1) signaling in pts with high-risk disease. Such features, linked with poorer prognosis and potential ET resistance, may be addressed through PD-1 inhibition combined with current SoC for pts with high-risk ER+, HER2− BC. Promising data assessing PD-1 inhibition coupled with neoadjuvant chemotherapy for pts with high-risk ER+, HER2− BC noted improved pathologic complete response (pCR) which is identified as a valid surrogate endpoint for long-term clinical outcomes. Trial Design: CheckMate 7FL is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 study evaluating nivolumab (NIVO) vs placebo (PBO) in combination with neoadjuvant chemotherapy and adjuvant ET in pts with high-risk, ER+, HER2− primary BC. Eligible pts are male or female, aged ≥18 years with newly diagnosed grade 2 with ER expression of 1-9%, or grade 3, T1c-2, cN1-2 (tumor size &amp;gt;2 cm) centrally confirmed ER+, HER2− BC. Pts eligible for neoadjuvant chemotherapy and surgery, with adequate organ function, ECOG PS of 0 or 1, and tissue available for biomarker assessments will be enrolled. Pts with history of ipsilateral invasive BC regardless of treatment, ipsilateral ductal carcinoma in situ treated with radiotherapy, contralateral invasive BC at any time, grade ≥1 peripheral neuropathy, or those with prior treatment for the currently diagnosed BC are excluded. Approximately 1200 pts will be randomized 1:1 to NIVO or PBO, stratified by programmed death ligand 1 (PD-L1) expression (+ or −), tumor grade (2 or 3), axillary nodal status (+ or −), and anthracycline + cyclophosphamide schedule (Q3W or Q2W). Node negative pts will be capped at 20% of the intent-to-treat population. In the neoadjuvant phase, pts will receive NIVO 360 mg Q3W or PBO plus paclitaxel 80 mg/m2 QW for four 3-week cycles, followed by NIVO 360 mg Q3W (or 240 mg Q2W) or matching PBO in combination with either doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 Q3W (or Q2W, respectively, dose-dense schedule option) for 4 cycles. Pts will undergo surgery after completion of the neoadjuvant phase. Following surgery, pts will enter the adjuvant phase and receive NIVO 480 mg Q4W or PBO for 7 cycles plus investigator’s choice of ET per local SoC. Primary endpoints are pCR, defined as no histologic evidence of invasive tumor cells in breast and axillary lymph nodes as well as non-axillary sentinel node (ypT0/is, ypN0) as determined by local pathologist, and event-free survival. Secondary endpoints include overall survival, disease-free survival, distant-metastasis-free survival, safety, pCR (ypT0 ypN0 and ypT0/is) rates, overall response rate, residual cancer burden, and quality of life. pCR rates will be compared using a 2-sided stratified Cochran-Mantel-Haenszel test with alpha = 0.01. Event-free survival will be compared using a stratified 2-sided log-rank test with adjusted alpha at each interim analysis and at final analysis. Recruitment worldwide is expected to begin in November 2019. For further information, please contact Kristen.Letrent@bms.com. Citation Format: Sherene Loi, Heather McArthur, Nadia Harbeck, Lajos Pusztai, Suzette Delaloge, Kristen Letrent, Tian Chen, Bin Li, Kay Tatsuoka, Dimitrios Zardavas, Giuseppe Curigliano. Nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-03.

Abstract GS3-01: Investigating denosumab as an add-on treatment to neoadjuvant chemotherapy and two different nab-paclitaxel schedules in a 2x2 design in primary breast cancer - First results of the GeparX study

Abstract Background Pharmacologic inhibition of the receptor RANK with denosumab can prevent or delay bone metastasis in patients with breast cancer (BC) and may improve disease-free survival in postmenopausal woman with hormone receptor (HR) positive BC. The GeparSepto study demonstrated an increased pCR rate after weekly nab-paclitaxel compared to weekly standard solvent-based paclitaxel, whereas the ETNA did not. It remains still unclear which administration regimen should be preferred for nab-paclitaxel. GeparX investigates whether the addition of denosumab to anthracycline/taxan-containing neoadjuvant chemotherapy (NACT) increases the pCR rate and which nab-paclitaxel schedule should be preferred for primary BC. Methods GeparX, a phase II study, was planned to randomize 778 patients to NACT+/-denosumab (120mg s.c. q4w for 6 cycles), stratified by lymphocyte predominant BC (≤50% vs &amp;gt;50% stromal tumor infiltrating lymphocytes [sTILs]), subtype (HER2-/HR+ vs triple negative (TNBC) vs HER2+), and epirubicin/cyclophosphamide (EC, q2w vs q3w). Secondarily, patients are randomized to different taxane backbones: nab-paclitaxel 125mg/m² weekly+EC or nab-paclitaxel 125mg/m² day 1,8 q22 (2/3)+EC. Carboplatin was given in TNBC and ABP 980 + pertuzumab (biosimilar substudy) in HER2+ BC. Patients with primary cT1c-cT4a-d BC and centrally assessed HR, HER2, Ki-67, and sTILs on core biopsy could be enrolled. Co-primary objectives compare the pCR (ypT0 ypN0) rates of NACT+/-denosumab and the pCR rates between the two backbone nab-paclitaxel treatments. Secondary objectives are interaction of denosumab treatment with RANK expression; pCR per arm for both randomizations in TNBC and HER2+ BC; pCR in RANK high vs low; other pCR definitions for both randomizations; response rates; breast conservation rates; toxicity and compliance; survival. The biosimilar substudy evaluates safety and efficacy of the biosimilar trastuzumab ABP 980 in combination with pertuzumab for HER2+ positive BC. Sample size (primary endpoint) planning assumed a pCR improvement by denosumab from 35% to 46% (OR=1.58; 2-sided α=0.10; 92% power) and by different nab-paclitaxel schedule from 36% to 45% (OR=1.45; 2-sided α=0.10; 80% power; overall α=0.20), requiring 778 patients (2-sided α=0.10; 80% power). Results A total of 780 patients were randomized between 2/2017 and 3/2019. Baseline characteristics were well balanced. Median age was 49.0 years [range 22-80]; 37.7% of patients had cT1, 56.3% cT2, 6.0% cT3/ T4, and 38.1% were cN+; G3 was reported in 66.5% and Ki-67 &amp;gt;20% in 83.1%; 7.9% of tumors showed &amp;gt;50% sTILs. 40.6% of patients had TNBC, 39.7% HER2/HR+ BC and 19.6% HER2+ BC. 343 serious adverse events (SAEs) in a total of 214 patients were reported. The rate of patients with at least one SAE was higher with nab-paclitaxel 125mg/m² weekly than in 2/3 weeks (30.8% vs 24.1%) irrespective of the addition of denosumab. The last patient will be operated at the beginning of October 2019. Conclusions The results of the primary endpoints and selected secondary endpoints will be presented at the meeting. Funding: The trial was financially supported by Amgen and Celgene Citation Format: Jens-Uwe Blohmer, Theresa Link, Sherko Kümmel, Michael Untch, Marianne Just, Peter A Fasching, Andreas Schneeweiss, Pauline Wimberger, Oliver Stötzer, Jens Huober, Marc Thill, Christian Jackisch, Kerstin Rhiem, Claus Hanusch, Carsten Denkert, Knut Engels, Valentina Nekljudova, Sibylle Loibl. Investigating denosumab as an add-on treatment to neoadjuvant chemotherapy and two different nab-paclitaxel schedules in a 2x2 design in primary breast cancer - First results of the GeparX study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-01.

Abstract P1-18-15: Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia: Interim analysis

Abstract Background: The addition of pertuzumab to trastuzumab for patients (pts) with HER2 +ve breast cancer results in higher rates of pathological complete response (pCR);although, it is not yet known if this translates into improved survival outcomes. In May 2016 pertuzumab was approved in Australia by the Therapeutic Goods Administration, in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of locally advanced and inflammatory HER2+ve breast cancer; and in September 2018, for early stage (&amp;gt;2cm diameter or node positive) disease. This study aims to capture real world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting. Methods: PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating or considering pertuzumab treatment in the neoadjuvant setting for non-metastatic HER2+ breast cancer. The primary objective is to assess the incidence rates of all adverse events (AEs) related to pertuzumab and the effectiveness of neoadjuvant pertuzumab when added to trastuzumab, in the real world setting. De-identified data obtained from the pts’ medical notes by the treating physician, were deposited to a centralized data capture tool (REDCaP), hosted at the Walter and Eliza Hall Institute of Medical Research. This interim analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of AEs related to pertuzumab. Secondary objectives include rates of breast or nodal surgery, relapse free survival (RFS) and overall survival (OS). Results: Ninety pts receiving neoadjuvant pertuzumab were enrolled for data capture between March 2018 and June 2019. Sixty-nine of these pts had data available for interim analysis by June 18th 2019 (Table). HER2-targeted neoadjuvant treatment was completed in 65/69 pts (94.2%) with a median [min-max] duration of 4 [1-6] cycles of pertuzumab and 5 [1-6] cycles of trastuzumab, and chemotherapy was administered in all 69 pts. The most common neoadjuvant chemotherapy regimens were taxanes + anthracyclines (n=30, 43.5%) and single agent taxane (n=26, 37.7%). Surgery was performed in 66/69 pts (95.7%). The bpCR was 71.2% and the total pCR rate was 66.7%. All pts who did not achieve a pCR obtained a partial response (28.8%). Total pCR was achieved by 20/26 (76.9%) hormone receptor-negative and 24/40 (60.0%) hormone receptor-positive pts. Three pts (4.3%) experienced at least one pertuzumab-related AE [cardiac toxicity (n=1, 1.4%), diarrhea (n=2, 2.9%), rash (n=1, 1.4%) and (sepsis n=1, 1.4%)] and all ceased pertuzumab. RFS and OS were 97.1% and 98.6% respectively, with a median follow up time from diagnosis of 16.1 [4-36.4] months. One patient did not undergo surgery due to a new non-breast cancer which resulted in death. Conclusion: This is the first multicenter, prospective, observational study to report pCR with pertuzumab in real world clinical practice in Australia. Neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non metastatic breast cancer achieved a total pCR rate of 66.7% and bpCR rate of 71.2%, which was numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the accepted safety profile for pertuzumab. Acknowledgment: Study sponsored by Roche Products, Pty. Limited Table: Patient and Tumor CharacteristicsCharacteristicNumber (%)Age51.8 (25.9-82.1)Charlson Comorbidity Index058 (84.1)18 (11.6)≥23 (4.4)Tumor Size (Clinical/Radiological staging)T1 (&amp;lt;2 cm)9 (13)T2 (2-5 cm)44 (63.8)T3 (&amp;gt;5 cm)14 (20.3)Unknown2 (2.9)Tumor Grade10 (0)220 (29.0)347 (68.1)Unknown2 (2.9)Nodal Status (Clinical/Radiological)Node positive46 (66.7)Node negative23 (33.3)Hormone Receptor StatusHR+42 (60.9)HR−27 (39.1)Median baseline left ventricular ejection fraction65%Patient cardiac risk factorsNo risk factor40 (58.0)1 risk factor14 (20.3)≥2 risk factors15 (21.7) Citation Format: Sheau Wen Lok, Richard De Boer, Sally Baron-Hay, Fran Boyle, Peter Button, Belinda Castles, Bianca Devitt, Peter Fox, Michael Harold, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter Gibbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia: Interim analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-15.

Abstract P1-01-02: Early changes in diffuse optical tomography predicts pathologic complete response to neoadjuvant chemotherapy in triple-negative breast cancer

Abstract Background: Optical based imaging modalities have shown promise for monitoring tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC). Patients with triple negative BC (TNBC) who achieve a pathologic complete response (pCR) have improved disease free and overall survival after NAC. In this study, we evaluated whether early changes in diffuse optical tomography breast imaging system (DOTBIS) parameters can predict a pCR. In particular, we studied total hemoglobin concentration (ctHbT) in the tumor region. Methods: This is a retrospective evaluation of 105 stage II-III BC patients enrolled in a prospective cohort study between 2011 and 2019. All patients received standard taxane-based chemotherapy in the neoadjuvant setting and pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Residual Cancer Burden (RCB) score was also calculated. By imaging the whole breast volume using low intensity near infrared light, we measured tissue concentration of oxy-hemoglobin (ctO2Hb) and deoxy-hemoglobin (ctHHb). After tumor volume segmentation, the mean ctHbT (ctO2Hb+ ctHHb) extracted from the region of interest was normalized by the non-tumor region ctHbT mean value. We conducted an independent-samples t-test to determine if there was a difference in changes in the normalized ctHbT levels at week 4 (w4) between patients with a pCR and non-pCR. A Pearson's correlation assessed for correlation between RCB score and changes in the normalized ctHbT level at w4 compared to baseline. Results: In total, 77 patients had complete data for the analysis. Of these, TNBC accounted for 18% (14/77) of BC cases. DOTBIS data was acquired at baseline for all patients. Twelve patients received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4, and two received docetaxel/cyclophosphamide every 3 weeks x 6. Ten of 14 TNBC patients were imaged after four weeks of taxane-based NAC (w4). Of the 14 TNBC patients, 6 (43%) achieved pCR. Two patients were classified as RCB-I, 5 as RCB-II, and 1 non-pCR patient without an available RCB. After comparing normalized ctHbT levels at w4 to baseline, NAC was associated with an overall decrease of 28% for the pCR group (n=5) as opposed to an increase of 67% for non-pCR (n=5). The normalized ratio between ctHbT levels measured at w4 and baseline was statistically lower in the pCR group (0.72 ± 0.28) than non-pCR (1.67 ± 0.83) (95% CI, 0.17 to 2.09), p = .043. Changes in the normalized ctHbT levels after 4 weeks of NAC were strongly correlated to RCB score (r = .833, p = .005). Conclusions: This study demonstrates that changes as early as 4 weeks in DOTBIS-measured ctHbT levels in patients with TNBC receiving NAC correlate strongly with pathologic response. If further validated on a larger set, these data could potentially be used to optimize treatment outcomes or improve personalized therapeutic strategies. Citation Format: Mirella L Altoe, Kevin Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna S Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Early changes in diffuse optical tomography predicts pathologic complete response to neoadjuvant chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-02.

24TiP - KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab or placebo with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage, ER+/HER2−breast cancer

24TiP - KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab or placebo with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk, early-stage, ER+/HER2−breast cancer

LBA8_PR - KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC)

LBA8_PR - KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC)

188P - Risk factors for locoregional recurrence (LRR) after neoadjuvant chemotherapy: Pooled analysis of prospective neoadjuvant breast cancer (BC) trials

188P - Risk factors for locoregional recurrence (LRR) after neoadjuvant chemotherapy: Pooled analysis of prospective neoadjuvant breast cancer (BC) trials