Higher pCR Rate Research Articles

Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer in a Nigerian Cohort

Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is a marker for important clinical outcomes in the management of breast cancer. In Nigeria where the majority of patients are candidates for NAC, there is limited data on pCR following NAC. This study evaluated the pCR rate in a cohort of Nigerian patients. Methods: A retrospective review of patients who had NAC and mastectomy for breast cancer between 2017 and 2022. Relevant baseline clinicopathological and treatment data were obtained, pCR was defined as the absence of invasive cancer with or without in situ disease in the breast. The relationship between receptor status, type of chemotherapy and pCR was evaluated. Results: One hundred and sixty six of the 250 patients who had mastectomy during the period had NAC and were eligible for analysis. The mean age was 50.1±11.1, the majority had stage 3 disease. Overall (pCR) rate was 19.9% with the latter part of the study corresponding to the period with increased use of taxanes, having higher pCR (35.9% in 2022 vs 7.4% in 2017, p=0.024). Patients with HER 2 positive/Hormone receptor negative (HER 2+/HR-), HER 2+/HR+ and triple negative disease had significantly higher pCR than those with HR+/HER 2 negative disease (38.9%, 30.8%, 24.5% and 6.5% respectively, p=0.03). Conclusion: NAC resulted in pCR in about one-fifth of the entire cohort, particularly those with potentially aggressive HER 2+ and triple negative disease. The use of taxanes was associated with higher pCR rates.

Induction Fluorouracil-Based Chemotherapy and PET-Adapted Consolidation Chemoradiation with Esophagectomy for High-Risk Gastroesophageal Adenocarcinoma.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials.

Relationship between the change in tumour-infiltrating lymphocyte level and residual tumour after neoadjuvant chemotherapy in patients with locally advanced breast cancer

To evaluate the tumour-infiltrating lymphocyte (TIL) rates in breast tissue before and after neoadjuvant chemotherapy (NAC) and their impact on survival, eighty-four patients with locally advanced breast cancer (LABC) were assessed. Pre- and post-NAC TIL levels were determined using biopsy and surgical specimens, respectively. The median TIL rate was significantly different before (17.5%) and after (5%) NAC. Pre- and postoperative Ki-67 index, molecular subtype, pre- and post-NAC TIL concentration, and preoperative residual-cancer-burden TIL were significantly associated with pathological complete response (pCR). Specifically, higher pre-NAC TIL levels were associated with higher pCR rates. Postoperative Ki-67 index and pCR, and postoperative Ki-67 index were significant predictors of disease-free (DFS) and overall survival, respectively. The independent prognostic factors for DFS were postoperative Ki-67 score (hazard ratio [HR]: 6.16; p = 0.012), post-NAC TIL score (HR: 0.42; P = 0.041), and pCR (HR: 0.10; P = 0.038). Our study confirms that higher pre-NAC and lower postoperative TIL levels may be surrogate factors for longer DFS, and postoperative TIL rate may predict post-NAC pCR in patients with LABC.

High-dose chemotherapy sensitizes locally advanced esophageal squamous cell carcinoma to PD-1 blockade for a higher pathological complete response rate and survival

BackgroundPD-1 inhibitor and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). The present study aimed to evaluate the efficacy of PD-1 inhibitors plus different dose intensity neoadjuvant chemotherapy in the treatment of locally advanced ESCC. MethodsPatients with locally advanced but resectable thoracic ESCC, staged as T3 or T4a, N0–3, and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes), were enrolled in this study. The eligible patients received tislelizumab plus different dose intensity chemotherapy for a 21-day cycle with repeated 2–4 cycles before surgery. The primary endpoints are pathological complete response (pCR) and major pathological response (MPR), and the secondary endpoints are objective response rate (ORR), disease control rate (DCR), and disease-free survival (DFS). ResultsFrom November 2019 to February 2022, 122 cases received at least two cycles neoadjuvant chemoimmunotherapy and were evaluated by imaging examination. Subsequently, 99 patients underwent surgery and were evaluated by pathological evaluation. According to chemotherapy dose intensity, the patients were divided into three cohorts: cohort 1 (<80% dose intensity), cohort 2 (80–90% dose intensity), cohort 3 (90–100% dose intensity). All surgery patients underwent minimally invasive esophagectomy (MIE). The average pCR was identified in 22.22%; 16% had pCR in cohort 1, 17.65% had pCR in cohort 2, and 30.00% had pCR in cohort 3. MPR was observed in 9 (36.00%) patients in cohort 1, 18 (52.94%) patients in cohort 2, 22 (55.00%) patients in cohort 3. In univariable and multivariable analysis, dose intensity was significantly associated with MPR (p = 0.048) in patients who underwent esophagectomy. For surviving patients, the median follow-up was 13.76 months after esophagectomy. Compared to cohort 1, cohorts 2 and 3 had better DFS (p = 0.056). In addition, the prognosis of patients with MPR was better than that of patients without MPR (p = 0.014). ConclusionsThe robust antitumor activity of neoadjuvant chemoimmunotherapy for locally advanced but resectable thoracic ESCC was confirmed. More than 80% of chemotherapy dose intensity combined with immunotherapy resulted in a high pCR rate and prolonged DFS.

Characteristics of pathologic complete response for locally advanced rectal cancer

BackgroundNeoadjuvant chemoradiation (NACRT) is the standard of care for locally advanced rectal cancers. The purpose of this study was to determine patient and tumor factors associated with a pathologic complete response (pCR). MethodsThe National Surgical Quality Improvement Program proctectomy-targeted database was utilized to identify all patients from 2016 to 2020 who underwent NACRT followed by proctectomy with curative intent for T3-4N0-2 rectal cancers. ResultsA total of 1891 patients were included, of which 253 (13.4%) demonstrated a pCR. Pretreatment N0 staging was associated with a higher rate of pCR (18.9%) when compared to N1 (6.7%) and N2 (6.7%) (p < 0.0001). Patients clinically staged at T3N0 had the highest rate of pCR (19.5%). Gender, age, race, weight, smoking status, and tumor height were not associated with pCR. ConclusionsPatients with cN0 disease were more likely to experience a pCR compared to cN1-2 patients. Tumor height relative to anal verge or patient demographics were not associated with pCR.

Androgen deprivation therapy plus abiraterone or docetaxel as neoadjuvant therapy for very-high-risk prostate cancer: a pooled analysis of two phase II trials.

Objective: The study aimed to compare the efficacy and safety of androgen deprivation therapy (ADT) with abiraterone or docetaxel versus ADT alone as neoadjuvant therapy in patients with very-high-risk localized prostate cancer. Methods: This was a pooled analysis of two single-center, randomized, controlled, phase II clinical trials (ClinicalTrials.gov: NCT04356430 and NCT04869371) conducted from December 2018 to March 2021. Eligible participants were randomly assigned to the intervention (ADT plus abiraterone or docetaxel) and control (ADT alone) groups at a 2:1 ratio. Efficacy was evaluated by pathological complete response (pCR), minimal residual disease (MRD), and 3-year biochemical progression-free survival (bPFS). Safety was also analyzed. Results: The study included 42 participants in the ADT group, 47 in the ADT plus docetaxel group, and 48 in the ADT plus abiraterone group. A total of 132 (96.4%) participants had very-high-risk prostate cancer, and 108 (78.8%) had locally advanced disease. The ADT plus docetaxel group (28%) and ADT plus abiraterone group (31%) had higher rates of pCR or MRD (p = 0.001 and p < 0.001) compared with the ADT group (2%). The 3-year bPFS was 41.9% (95% CI: 26.6-57.2), 51.1% (95% CI: 36.8-65.4), and 61.2% (95% CI: 45.5-76.9), respectively. Significant difference was found among groups in terms of bPFS (p = 0.037). Conclusion: Compared with ADT alone, neoadjuvant therapy with ADT plus docetaxel or abiraterone could achieve better pathological outcomes (pCR or MRD) for very-high-risk localized prostate cancer. The ADT plus abiraterone group showed longer bPFS than ADT alone. The combination regimens were tolerable.

The Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.

The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC. We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates. In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used. Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabetic status.

Pretreatment high cholesterol and low neutrophils predict complete pathological response after neoadjuvant short‑course radiotherapy followed by chemotherapy and immunotherapy in locally advanced rectal cancer.

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

Real-world, single-center experience on the outcomes of neoadjuvant chemotherapy and trastuzumab alone or in combination with pertuzumab in human epidermal growth factor receptor-2 breast cancer patients.

e12589 Background: Neoadjuvant chemotherapy (NACT) is the standard of care for early-stage breast cancer (BC). Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of BC patients, and HER2 overexpression is associated with poor prognosis. The introduction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ BC. NACT in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival rates. Methods: We performed a retrospective review of HER2+ BC patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ BC patients who received NACT with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received neoadjuvant single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) anti-HER2 therapy, respectively. The majority of patients were aged &lt; 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category [Invasive ductal carcinoma (IDC) being most common] and Ki67 status for both groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p = 0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade versus single-blockade group (50% vs. 39.2%; p = 0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% each, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3% respectively. Conclusions: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. [Table: see text]

Magnetic resonance imaging tumor regression shrinkage patterns during neoadjuvant chemotherapy versus neoadjuvant immunochemotherapy in triple-negative breast cancer (NeoMDSS-TN-SP): A nonrandomized, prospective cohort study.

e12601 Background: Previous studies have shown that the tumor regression shrinkage pattern (SP) of triple-negative breast cancer (TNBC) during neoadjuvant chemotherapy (NAC) is more likely to present with concentric shrinkage (CS), which is associated with a pathological complete response (pCR). Since immunotherapy and chemotherapy have different antitumor mechanisms, it is reasonable to believe that there may be different SPs between neoadjuvant immunochemotherapy (NAIC) and NAC. This NeoMDSS-TN-SP prospective study aimed to investigate whether tumor SPs differed between NAIC and NAC in TNBC, as well as to calculate the correlation between SP and efficacy. Methods: In this prospective, single-center, nonrandomized cohort study, eligible patients with stage II-III TNBC received NAIC or NAC and underwent MRI at baseline, after the first cycle of neoadjuvant therapy, and preoperatively. Based on the MRI after the first cycle, the tumor SPs were grouped into three categories: CS, diffuse decrease, and no change or enlargement. The primary end point was the difference in SP between the two treatment groups. Secondary endpoints included the correlation between SP and treatment efficacy. This study is registered with ClinicalTrials.gov, number NCT04909554. Results: Ninety-nine patients were enrolled from January 2019 to July 2021; 65 received NAC and 34 received NAIC. Baseline characteristics were similar between the two groups. More patients in the NAIC group achieved pCR after surgery than in the NAC group (82.4% vs. 44.6%, p=0.0003). In the NAC group, more patients showed CS (53.8%), and patients with the CS pattern had a significantly higher pCR rate than those with diffuse decrease or no change/enlargement (65.7% vs. 21.7% vs. 14.3%, p=0.0007). In the NAIC group, although a higher proportion of patients showed diffuse decrease (67.6%), all three SP categories had relatively high pCR rates, so pCR was not correlated with SP (85.7% vs. 82.6% vs. 75.0%, p=0.9029). Conclusions: This is the first study to investigate the tumor regression SP of NAIC in TNBC patients. Compared to traditional chemotherapy, NAIC was more prone to diffuse regression, but the relatively high pCR rates had no correlation with the SPs during neoadjuvant therapy. Clinical trial information: NCT04909554 . [Table: see text]

Pathologic complete response in germline mutation carriers by mutation type and biomarkers in a safety-net population.

e12628 Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy in early to locally advanced breast cancer has important prognostic implications with high cure rates. Understanding its associations with hereditary breast cancer mutations, specifically by mutation type and biomarkers, adds additional prognostic value. In this retrospective chart review, we investigated pCR rates among patients who have undergone genetic testing in a safety-net hospital comprised primarily of racial minorities. Methods: All patients at Smith Clinic (affiliated with the Harris County’s safety-net hospital system) with a diagnosis of stage I-III breast cancer who agreed to undergo genetic testing, were found to have a genetic mutation from October 1, 2009 to September 30, 2019, and received neoadjuvant chemotherapy followed by lumpectomy or mastectomy were included. Demographic and clinical characteristics as well as post-operative pathologic data were collected. Results: 71 patients qualified for the analysis. 50 (70%) were Hispanic, and the median age was 42. 41 (58%) were BRCA1+, 13 (18.3%) were BRCA2+, and 12 (16.9%) were PALB2+. They ranged from stage I-III, with 49% falling in stage III. In terms of biomarker status, triple negative breast cancer (TNBC) comprised 35 (49%) patients, HER2+ 8 (11%), and ER+ and/or PR+ (HER2-) 28 (39%). 36 (51%) were treated with both neoadjuvant anthracycline and taxanes. pCR rates were highest among triple negative cancers (17, 48%). 16 (39%) of patients with a BRCA1 mutation achieved pCR, 5 (38.5%) of BRCA2 patients and 3 (25%) of PALB2 patients. RCB class by mutation type and biomarker status will be reported as well as a more detailed analysis of pCR by mutation status and biomarkers. Conclusions: In our population of primarily Hispanic patients, those with BRCA1, BRCA2, and PALB2 had the highest pCR rates. As expected, patients with TNBC had the highest pCR rates. More data in patients with germline mutations may help us determine prognosis and how to best treat these patients. [Table: see text]

A phase II study of weekly carboplatin and nab-paclitaxel with trastuzumab or bevacizumab as neoadjuvant therapy for patients with early-stage nonmetastatic breast cancer.

e12623 Background: Neo-Adjuvant chemotherapy (NAC) allows patients to undergo breast conserving surgery, treats micro metastatic disease and improves patient outcomes. Achieving a complete pathologic response to NACT has prognostic significance in HER2+ and triple negative breast cancer. Anthracyclines are commonly integrated to Neo-adjuvant regimens. Their use is limited by cardiac and hematologic toxicity. We proposed that weekly Carboplatin and Nab-Paclitaxel is a well-tolerated regimen and aim to demonstrate that this approach can be a selective anthracycline sparing regimen with comparable improvement in recurrence free survival (RFS) and pathologic complete response (pCR). Methods: We conducted a single institution, open label, prospective Phase II clinical trial for patients with non-metastatic breast cancer who were eligible to receive NACT. All Patients with stage I-III breast cancers were treated with weekly Nab-paclitaxel (90 mg/m2) and carboplatin (AUC 2) for 12 weeks. Patients with HER2+ breast cancer received trastuzumab (4 mg/kg induction, followed by 2 mg/kg/week) weekly for 12 weeks. Triple negative and HR + patients received bevacizumab (10 mg/kg) every other week for 5 doses. Results: We enrolled 125 patients from February 2008 to December 2015. 85 pts were HER2- and 42 pts were HER2+. The pCR rate was 17.6% (15 pts) in the HER2- cohort and 50% (21 pts) in the HER2+ cohort. In the subgroup analysis based on hormone receptor (HR) status, pts with HR- tumor had more favorable response with higher rate of pCR compared with pts with HR+ tumor. In the HER2- cohort, the total pCR rate was 34% in HR- tumors vs 8% in HR+ tumors, P = 0.0018. After a median follow up of 53 months, overall survival was 88.9% for pts who achieved pCR and 77.7% for those who did not. HR = 0.3664, CI = 0.06147 to 2.1843, P = 0.34.In the HER2+ cohort the pCR rate was 33% in pts with HR+ tumors vs 72% in pts with HR- tumor, P = 0.0137. After a median follow up of 53 months, overall survival was 100% for pts who achieved pCR vs 20% in those who did not. The relapse-free survival was 90% vs 25% respectively (HR = 0.0669, CI = 0.00454 to 0.9251 P = 0.0016). In the entire study population, 6 pts (4.7%) had treatment discontinuation and 12 pts (9.4%) had dose reduction due to side effects. The rate of treatment disruption was higher in the HER2- cohort. Nausea, vomiting, and neutropenia were the most common side effects in both cohorts (7.9%) followed by thrombocytopenia and anemia (4.7%). Hematologic toxicity was the most common toxicity grade 3 and 4. Conclusions: Combination of nab-paclitaxel and carboplatin plus targeted therapy as an anthracycline sparing neoadjuvant chemotherapy showed a good pCR rate in HER2+ subgroup and moderate activity in TNBC subset. High rate of pCR was associated with high survival outcomes in HER2+ cohort. The regimen was well tolerated among both cohorts. Clinical trial information: NCT00618657 .

Predictive value of tumor-infiltrating lymphocyte (TIL) dynamics in the tumor microenvironment (TME) during preoperative chemoradiotherapy (CRT) on pathologic complete response (pCR) in microsatellite-stable (MSS) locally advanced rectal cancer (LARC).

3608 Background: Preoperative CRT followed by consolidation nivolumab before surgery showed a promising pCR rate in MSS LARC; both high PD-L1 expression and an elevated CD8+ T cell/effector regulatory T cell ratio analyzed by pre-CRT samples were independently related to high pCR rate (Bando H, Clin Cancer Res. 2022). Here, we applied AI-powered spatial TIL analysis to the VOLTAGE study to investigate whether dynamic change of TIL in TME may predict pCR in MSS LARC. Methods: The VOLTAGE study is a multicenter phase I/II study to evaluate the efficacy of CRT followed by 5 cycles of nivolumab and surgery in patients (pts) with LARC. In this study, tumor samples were obtained at multiple time points; pre-CRT (B1), post-CRT/pre-nivolumab (B2), post-3 cycles of nivolumab (B3), and surgery. In this analysis, a total of 86 H&amp;E whole-slide images (WSI) harvested at B1 and B2 time points from all the pts enrolled in the VOLTAGE study were included in the analysis. Lunit SCOPE IO (Lunit, Republic of Korea), AI-powered H&amp;E-WSI analyzer developed based on 16,443 WSI with pathologists' annotations, was applied to quantify TIL density in TME. Results: In a total of 43 pts, pCR rate of MSS and microsatellite instability-high (MSI-H) were 28.9% (11/38) and 60% (3/5), respectively. In MSS subgroup (n = 38), which has a higher unmet need for pCR prediction, tumor samples with pCR (n = 11) had increased TIL density in TME (tTIL) in post-CRT (B2, median [IQR] 726 [249-1607] /mm2) compared to pre-CRT (B1, 598 [366-905] /mm2), whereas those without pCR (n = 27) had decreased tTIL in post-CRT (405 [148-748] /mm2), compared to pre-CRT (B1, 748 [460-1153] /mm2). Intratumoral TIL density changes were more prominent than stromal TIL density changes in MSS tumor samples with pCR (mean fold change x17.7 vs. x1.5). MSS Pts with tTIL change from B1 to B2 (during CRT) more than x1.8 times achieved 75% (6/8) pCR rate, whereas those with tTIL change less than x1.8 had 16.7% (5/30) pCR rate (p = 0.0035). Conclusions: Change of TIL density in TME during CRT was significantly correlated with favorable clinical outcome of preoperative CRT and consolidation nivolumab, resulting in high pCR rate in MSS LARC.

The relationship between the change with neoadjuvant chemotherapy in the tumor-infiltrating lymphocyte (TIL) expressions and pathological response in breast cancer patients.

3114 Background: Many prognostic biomarkers for survival have been studied in the neoadjuvant setting for locally advanced breast cancer (LABC). Our study assessed the correlation between the change in tumour-infiltrating lymphocytes (TIL) before and after neoadjuvant chemotherapy (NAC) in breast tissue and its impact on survival in patients with LABC. Methods: Eighty-four LACB patients were retrospectively analysed in this study. TIL was assessed by means of immunohystochemistry (Eclipse Ni, Nikon, Japan) in paraffin-embedded blocks obtained by core-needle biopsy or surgical specimen with respect to the 'TIL working group' criteria. Results: TIL scores were grouped as 0%, &lt;10%, 10-50%, and &gt;50%, the median TIL percentage was 17.5% before NAC and 5% after NAC, and the difference was statistically significant (p&lt;0.001). Postop-Ki-67 (p=0.005), molecular subtype (p=0.027), pre-NAC TIL score (p=0.006), post-NAC TIL score (p&lt;0.001), postop-Ki-67 (p=0.005) and preoperative residual cancer burden tumour-infiltrating lymphocyte (RCB-TIL) (p&lt;0.001) were significantly correlated with pCR. Higher TIL scores were significantly associated with higher PCR rates. Univariate analysis for disease-free survival (DFS) and overall survival (OS) revealed that postop-Ki-67 level and presence of pCR and postoperative ki-67 score (p=0.031) were significant prognostic factors, respectively. The independent prognostic factor for DFS were postop-Ki-67 score (p=0.012, RR: 6.16, 95% CI: 1.48-9.12), post-NAC TIL score (p=0.041, RR: 0.42, 95% CI: 0.16-1.06) and the presence of pCR (p=0.038, RR: 0.10, 95% CI: 0.01-0.87). Logistic regression analysis showed that a preoperative ki-67 score greater than 14% (p=0.001, OR: 4.55; 95% CI: 0.11-1.49), a postoperative ki-67 score equal to or lower than 14% (p=0.011, OR: 1.10; 95% CI: 0.42-2.29), preop-grade 3 (p=0.01, OR: 2.65; 95% CI: 0.85-3.14), low postop-TIL score (p&lt;0.001, OR: 3.14; 95% CI: 0.79-4.11) were significant predictive factors for pCR. Conclusions: Our study confirms the hypothesis that TIL expressions may be therapeutic targets, especially in specific molecular breast cancer subtypes.

Efficacy, cardiotoxicity and factors affecting pathologic complete response of neoadjuvant chemotherapy with anthracycline-containing verses anthracycline-free regimens plus dual HER2 blockade for HER2-positive early-stage breast cancer: a retrospective study.

The aim of this study was to compare the efficacy, cardiotoxicity and factors affecting pathologic complete response (pCR) of neoadjuvant chemotherapy (NACT) regimen TCbHP (docetaxel/nab-paclitaxel, carboplatin, trastuzumab and pertuzumab) and AC-THP (doxorubicin, cyclophosphamide followed by docetaxel/nab-paclitaxel, trastuzumab and pertuzumab) for human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer at a retrospective cohort. This retrospective study included the patients with HER2+ early-stage breast cancer who received NACT with the regimen TCbHP or AC-THP and then underwent surgery from 2019 to 2022. pCR rate and breast-conserving rate were calculated to evaluate the efficacy of the regimens. Left ventricular ejection fraction (LVEF) from echocardiograms and abnormal electrocardiographs (ECGs) were collected to evaluate the cardiotoxicity of the two regimens. Association between the characteristics of the breast cancer lesions by magnetic resonance imaging (MRI) and the pCR rate were also explored. A total of 159 patients were enrolled, including 48 patients in the AC-THP group and 111 patients in the TCbHP group. The pCR rate of the TCbHP group 64.0% (71/111) was significantly higher than that of for the the AC-THP group 37.5% (18/48) (P=0.002). Estrogen receptor (ER) status (P=0.011, OR: 0.437, 95% CI: 0.231-0.829), progesterone receptor (PR) status (P=0.001, OR: 0.309, 95% CI: 0.157-0.608) and IHC HER2 status (P=0.003, OR: 7.167, 95% CI: 1.970-26.076) were significantly correlated with the pCR rate. LVEF decreased at 6 and 12 months after treatment in the AC-THP group (P=0.024 and 0.040), which only decreased after 6 months of treatment in the TCbHP group (P=0.048). Post-NACT MRI characteristics including mass features (P<0.001) and enhancement type (P<0.001) were significantly associated with pCR rate. Early-stage HER2+ breast cancer treated with the TCbHP regimen has a higher pCR rate than the AC-THP group. The TCbHP regimen appears to have lower cardiotoxicity than the AC-THP regimen in terms of LVEF. Mass features and enhancement type at post-NACT MRI significantly associated with the pCR rate of breast cancer patients.

Perioperative PD-1 antibody toripalimab plus SOX or XELOX chemotherapy versus SOX or XELOX alone for locally advanced gastric or gastro-oesophageal junction cancer: Results from a prospective, randomized, open-label, phase II trial.

4001 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric or gastro-oesophageal junction (GEJ) cancer, but has not yet been investigated in the context of locally advanced patients. In this study, we conducted a prospective, randomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable gastric or GEJ cancer. Methods: In this randomized, open-label, phase II study, patients with resectable gastric or GEJ cancer clinically staged as cT3-4a N+M0 were randomized (1:1) to three preoperative and five postoperative 3-week cycles of SOX/XELOX (C arm) or PD-1 antibody toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for 6 months (C+T arm). The primary endpoint was pathological complete regression/moderate regression rate (TRG 0/1). The secondary endpoints were pathological complete response (pCR), R0 resection rate, recurrence-free survival, event-free survival, objective response rate, disease control rate, overall survival and treatment safety. The study had been completed enrollment, and here, we analyzed the primary endpoint. Mantel-Haenszel test was used to test the difference of pathological regression between the two arms. The trial was registered at ClinicalTrials.gov, identifier: NCT04250948. Results: Between Oct 2019 and June 2022, 108 patients (C+T arm, n=54; C arm, n=54) were enrolled and assessed using intention-to-treat analysis. Patients in the toripalimab plus chemotherapy arm achieved higher proportion of TRG 0/1 than those in the chemotherapy arm (44.4% [24/54, 95% CI: 30.9%-58.6%] vs 20.4% [11/54, 95% CI: 10.6%-33.5%]; P=0.009). A higher pCR rate was observed in the C+T arm (24.1% [13/54, 95% CI:13.5%-37.6%] vs 9.3% [5/54, 95% CI: 3.1%-20.3%]; P=0.039). Preoperative therapies (3 cycles) were completed in 96.3% of patients and postoperative cycles (&gt;3 cycles) in 81.5%, with no significant differences observed between these two arms. A higher proportion of downstaging was observed in the C+T arm (ypT0-2: 46.3% vs 22.2% [P=0.002]; ypstage 0-1: 38.9% vs 16.7% [P=0.024]). Surgical morbidity (11.8% in the C+T arm vs 13.5% in the C arm) and mortality (1.9% vs 0%) and treatment-related grade 3-4 adverse events (27.8% vs 25.9%) were comparable between the arms. Conclusions: Perioperative PD-1 antibody toripalimab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable gastric or GEJ cancer. Clinical trial information: NCT04250948 .

Radiation therapy (RT)-free pembrolizumab plus chemotherapy (P+C) for PD-L1 TPS ≥50% locally advanced non-small cell lung cancer (LA-NSCLC): An early report analyzing depth of response from multicenter single arm phase II study (Evolution trial: WJOG11819L).

8544 Background: Standard of care for unresectable LA-NSCLC is chemoradiation therapy (CRT) followed by durvalumab (D). Survival curves of P monotherapy/P+C for PD-L1 TPS ≥50% stage IV NSCLC suggested possible comparable survival to CRT for stage III patients (pts). Moreover, some studies of neoadjuvant C+immunotherapy (I) for stage III pts have demonstrated high pCR and MPR rates, implying potentially outstanding efficacy of C+I for earlier stage. We thus hypothesized P+C without RT in PD-L1 ≥50% LA-NSCLC pts provides a comparable efficacy to CRT followed by D while avoiding CRT-induced severe toxicities. Methods: This early report focuses on depth of response in a phase II study by WJOG. P with platinum plus pemetrexed (PEM) (non-squamous) or P with carboplatin plus nab-paclitaxel (squamous) was administered every 3 weeks without RT. After four cycles of induction P+C, P with PEM (non-squamous) or P alone (squamous) was continued until progression or 2 years. The primary endpoint was PFS rate at 2 years. Results: Between May 2020 and February 2022, 21 pts were enrolled. Median age was 74 (range, 53-89). Stage IIIA/B/C included 12 (57%)/6 (29%)/3 (14%), respectively. Histologic subtypes were 13 (62%) adeno, 5 (24%) squamous, and 3 (14%) others. Investigator-assessed best response: 8 (38%) CR; 10 (48%) PR; 2 (10%) SD; and 1 (5%) NE were confirmed, resulting in response rate (RR) of 86% and disease control rate of 95%. RR of TPS 50-79% and 80-100% were 78% and 92%, respectively. Deep response (DR): defined as tumor shrinkage ≥80% was obtained in 12 (57%) of 21 pts. DR was accomplished in 4 (44%) of 9 TPS 50-79% and 8 (67%) of 12 TPS 80-100%. Median time to response was 43 (range, 41-92) days. Early tumor shrinkage (ETS): PR-in at the time of first CT evaluation (6 weeks) was achieved in 16 (89%) of 18 CR+PR pts. At the time of data cut-off, median follow-up period was 18.5 (range, 0.3-29.0) months, and 14 (67%) of 21 pts were progression-free. All 12 pts achieving DR, including all 8 CR were progression-free, also in 14 (88%) of 16 ETS pts. Three pts after local progression received salvage definitive-CRT. Median number of P administrations was 20 (range, 1-35). AEs ≥grade 3 were observed in 11 (52%) pts, including: 2 (10%) pneumonitis; 2 (10%) pneumonia; 1 (5%) diarrhea; 1 (5%) ALT elevation; and 1 (5%) acute heart failure, excluding hematological AEs. There was one (5%) possible grade 5 AE (pneumonia). Conclusions: RT-free P+C exerted a notably high RR, including some CRs. The deeper/earlier response and higher PD-L1 TPS could be associated with the higher progression-free incidence at the data cut-off. To investigate our hypothesis: RT-free P+C can be a less toxic curative option in selected LA-NSCLC pts with PD-L1 TPS ≥50%, further matured data is warranted. Clinical trial information: NCT04153734 .

Neoadjuvant camrelizumab plus chemotherapy for locally advanced cervical cancer (NACI study): A prospective, single-arm, phase II trial.

5520 Background: First-line treatments for locally advanced cervical cancer (LACC) have limited efficacy and neoadjuvant chemotherapy (NACT) is an emerging approach, however, two-thirds of patients (pts) respond to it and pts without response benefit little. PD-1 inhibitors have shown promising role in recurrent or metastatic cervical cancer. This study aims to evaluate the efficacy and safety of preoperative PD-1 inhibitor camrelizumab combined neoadjuvant therapy for LACC. Methods: The study is designed as a multicenter, open-label, single-arm, prospective phase II study. Pts are enrolled if they had previously untreated LACC (2018 FIGO staged IB3, IIA2 and IIB/IIIC1r (tumor size &gt; 4cm). Eligible pts will receive neoadjuvant chemo-immunotherapy (NACIT), defined as one cycle of cisplatin (75-80 mg/m2, iv) plus nab-paclitaxel (260 mg/m2, iv) NACT and subsequent two cycles of camrelizumab (200mg, iv) combined NACT. Either surgery or concurrent chemoradiotherapy are conducted according to the response as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. The primary endpoint was objective response rate (ORR), and the secondary endpoints were pathological complete remission (pCR) rate, rate of postoperative adjuvant treatment, event-free survival, overall survival and safety. Results: From Dec 1, 2020 to Feb 1, 2023, 83 pts were enrolled, and 78 pts were evaluated for response. The ORR was 100% (95%CI, 95.38 to 100), with 14 (17.95%) complete response (CR) and 64 (82.05%) partial response. Regarding the pathological findings of 76 pts who underwent radical surgery, 30 (39.47% (95%CI, 28.44 to 51.35)) pts achieved pCR, while 17 (22.37%) needed postoperative adjuvant treatment as indicated in NCCN guideline, of who 14 had positive pelvic nodes, positive surgical margin, and/or positive parametrium and the other three met Sedlis criteria. RECIST CR was significantly associated with pCR ( P = 0.016). Pre-treatment PD-L1 expression (Combined Positive Score) was a predictive biomarker for RECIST CR ( P = 0.036) but not for pCR ( P = 0.078) in these evaluated patients. Grade 3 or 4 treatment-related adverse events occurred in 35 (44.87%) pts during NACIT; the most common were lymphocytopia (25.64%), neutropenia (12.82%) and leucopenia (8.97%). Conclusions: NACIT for LACC demonstrated extremely high ORR and pCR rate with manageable toxicity profile, and greatly reduced the need of postoperative adjuvant therapy. Clinical trial information: NCT04516616 .

Stereotactic body radiation therapy with sequential immunochemotherapy as neoadjuvant therapy in resectable non-small cell lung cancer (SACTION-01 study).

8540 Background: Neoadjuvant PD-1 inhibitor plus chemotherapy increases pathological response for resectable non-small cell lung cancer (NSCLC) compared with chemotherapy alone. Previous phase II trial indicated that stereotactic body radiation therapy (SBRT) served as an immunomodulator and enhanced the effect of preoperative immuno-monotherapy. However, whether SBRT would further increase the efficacy of immunochemotherapy for NSCLC remains unknown. Methods: In this phase II trial, patients with resectable EGFR wild-type stage IIA to IIIB NSCLC were recruited to receive SBRT (24 Gy in 3 daily fractions) to the primary tumor followed by two cycles of PD-1 inhibitor tislelizumab (200 mg) plus platinum-based doublet chemotherapy (Q3W) before surgical resection. The primary endpoint was major pathological response (MPR) defined as no more than 10% of viable tumor cells in the specimen. Simon’s optimal two-stage design was used for conducting the trial. The null hypothesis was that the MPR rate is 0.30, and the alternative hypothesis was that the true MPR rate was 0.50. More than 4 MPRs were needed in stage 1 (n=15) to continue, and if there were 19 or more MPRs in 46 patients by the end of stage 2, the null hypothesis can be rejected. The design controls the type I error rate at 0.05 and yields the power of 0.80. (NCT05319574). Results: Between May 2022 and Jan 2023, 32 patients were enrolled with 31 (96.9%) male and 19 (59.4%) having squamous cell lung cancer. Twenty-six (81.3%) patients had stage IIIA/B disease. All patients received at least one cycle of immunochemotherapy; 23 of the 25 patients (92.0%) who completed treatment had undergone R0 resections, except for one patient who had disease progression and the other one that unable to tolerate surgery because of grade 4 neutropenia. Twenty-two patients underwent minimally invasive approaches and 3 of them (13.6%) converted to thoracotomy. The median percentage of the viable tumor was 0 (interquartile range: 0-4.0%). Twenty patients achieved MPR, which surpassed the prespecified required number to reject the null hypothesis, resulting in the MPR rate of 80.0% (20/25) in the intention-to-treat population, and 87.0% (20/23) in the per-protocol population. Pathological complete response (pCR) was found in 14 patients (56.0% in the intention-to-treat population and 60.9% in the per-protocol population). Nodal clearance status (pN0) was found in 20 of 23 cN1/2 cases (87.0%). Grade 3-4 adverse events related to neoadjuvant treatment included neutropenia (13.0%), anemia (4.3%), and pneumonia (4.3%). No 30-day or 90-day mortality was observed. Conclusions: Neoadjuvant SBRT followed by immunochemotherapy yields unprecedently high MPR and pCR rates in NSCLC without EGFR mutation. The trial will continue to recruit 14 more patients to reach a final sample size of 46 participants. Clinical trial information: NCT05319574 .

Trimodality Therapy Improves Disease Control in Radiation-Associated Angiosarcoma of the Breast.

To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P < 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3-44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.