Cycles Of Neoadjuvant Therapy Research Articles

Abstract PO5-18-09: Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial

Abstract Background Anthracycline and taxane-based chemotherapy are the corner stone of neoadjuvant therapy in early breast cancer. Anthracycline-free regimens have been addressed widely because of cardiac toxicity especially in HER2-positive breast cancer when combining trastuzumab and pertuzumab. Aim of this trial was to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of non-luminal breast cancer. Methods The Neopath trial was a prospective, single-arm phase II trial conducted in Comprehensive Breast Health Center, Ruijin Hospital between April 2019 and October 2021. Patients who had cT2-4NanyM0 or cTanyN1-3M0 triple negative breast cancer (TNBC) or HER2-positive breast cancer were enrolled. Patients were treated with neoadjuvant nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve 2) on days 1, 8, and 15, for four 4-week cycles. Concurrent trastuzumab at 2 mg/kg (loading dose 4 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) were given in patients with HER2-positive tumors. Surgery was performed after 4-6 cycles of neoadjuvant therapy. Trastuzumab and pertuzumab after surgery was continued every 3 weeks for a total duration of 1 year. The primary endpoint was pathological complete response (pCR) rate, defined as no invasive tumor in breast and axillary lymph nodes (ypT0/Tis N0) after neoadjuvant therapy. Secondary endpoints were pCR rate in predefined subgroups, pCR (ypT0 N0), objective response rate (ORR); event-free survival (EFS), breast conservation rate and toxicity. Results A total of 106 patients were enrolled in the study and 99 of them proceeded to surgery. The pCR (ypT0/is N0) rate was 41.41% in total, 33.78% in TNBC and 64.00% in HER2-positive breast cancer. Proportion of patients achieving pCR (ypT0 N0) was 38.38% in total, 31.08% in TNBC and 60.00% in HER2-positive tumors. In the ITT population, 93 patients were event-free at a median follow-up of 24 months, while 5 in TNBC group and 1 in HER2-positive group had relapse or distant metastasis. EFS in patients achieving pCR was higher than patients without pCR (HR=7.328, 95%CI=1.453-36.96, p=0.0158). ORR was 72.49% in total, 67.12% in TNBC and 88.00% in HER2-positive breast cancer. Total breast conservation rate was 10.1% and 12.2% in TNBC, 4.0% in HER2-positive subgroup. The most frequent grade 3 or higher adverse events were neutropenia (57%), vomiting (11%) and thrombocytopenia (8%). Conclusion Neoadjuvant anthracycline-free regimen of nab-paclitaxel combined with carboplatin in non-luminal breast cancer was an effective and well-tolerated regimen. Citation Format: Deyue Liu, Li Zhu, Jiayi Wu, Wei Wang, Shuning Ding. Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-09.

Abstract PO3-18-11: A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

Abstract Background: Patients with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than patients who have a pathologic complete response (pCR). Escalation of therapy in patients with RD using post-neoadjuvant T-DM1 has become the new standard of care, leading to improved invasive disease-free survival (iDFS), but patients with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes, and central nervous system recurrences are a challenge. More effective treatment strategies are urgently needed. Alliance A011801 (CompassHER2 RD) is an escalation trial for patients with high-risk HER2+ RD after neoadjuvant systemic therapy, evaluating the addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to post-neoadjuvant T-DM1. Methods: Eligibility and Intervention: Patients with high-risk HER2+ RD (i.e., ER-, node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 + placebo, vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of paclitaxel and trastuzumab +/- pertuzumab. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (~15-30% will be participants in the CompassHER2 pCR de-escalation companion trial [NCT04266249]; these patients must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801). Patients who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is improved with addition of tucatinib to T-DM1 in patients with HER2+ EBC with RD after neoadjuvant systemic therapy; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in patients with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints are also being evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-), and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% & 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 patients; activation and estimated completion dates are 01/6/21 and ~ 01/2028. Accrual as of 7/10/2023: 438 patients. Support: U10CA180821, U10CA180882; Seagen Inc; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT04457596 Citation Format: Ciara O'Sullivan, Karla Ballman, Linda McCall, Tyler Zemla, Anna Weiss, Melissa Mitchell, Victoria Blinder, Nadine Tung, William Irvin, Myounghee Lee, Sailaja Kamaraju, Matthew Goetz, W. Fraser Symmans, Virginia Borges, Ian Krop, Ann Partridge, Lisa Carey. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-11.

Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial

In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.

Phase Ⅱ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Abstract CT209: Camrelizumab plus chemotherapy as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): A single-center, randomized, phase II trial

Abstract Background:Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery poses the standard treatment for resectable LA-ESCC. However, post-surgery recurrence remains a concern. The phase III ESCORT-1st trial demonstrated improved survival outcomes on the addition of camrelizumab to first-line chemotherapy over chemotherapy alone. This study aims to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by surgery in resectable LA-ESCC. Methods:In this single-center, open-label, randomized, two-arm, phase II trial, patients with resectable thoracic LA-ESCC (T3-4a or TxN+M0, except T4b) were 1:1 randomized to two groups for 3 cycles of neoadjuvant therapy, each lasting 3 weeks. Group A was treated with a combination of camrelizumab (200 mg, day 1), paclitaxel (80 mg/m², days 1 and 8), and cisplatin (75 mg/m², day 1). Group B received the same dose of camrelizumab and cisplatin, with albumin-bound paclitaxel (130 mg/m², days 1 and 8) instead. Surgery was scheduled within 3-10 weeks after the completion of neoadjuvant therapy. Adjuvant treatment was determined by the investigators, based on postoperative pathological findings. For biomarker analysis, blood and tissue samples were collected at baseline, after 2 cycles of neoadjuvant therapy, and postoperatively. The primary endpoint was the correlation between biomarkers and pathologic complete response (pCR, defined as ypT0N0). The second endpoints included event-free survival, overall survival, and safety. Clinical trial information: NCT04937673 Results:From June 2021 to April 2023, a total of 40 patients were enrolled: 20 patients in each group. By data cutoff on July 31st 2023, 19 patients in group A had completed 3 cycles of neoadjuvant therapy; 17 underwent surgery, with 2 refusals and 1 COVID-19-related delay. In group B, 17 patients completed neoadjuvant therapy, and surgery was performed on 14 patients with 5 refusals and 1 exclusion by investigators. R0 resection was achieved in 16 (94.1%) patients from group A and 14 (100.0%) from group B. In intention-to-treatment (ITT) analysis set, the pCR rate was numerically higher in groups A (30.0% [95%CI: 11.9- 54.3%]) compared to group B (10.0% [95%CI: 1.2-31.7%]). Similarly, a major pathologic response (tumor residual ≤10%) was observed in 50.0% (95% CI: 27.2-72.8%) of group A and 35.0% (95% CI: 15.4-59.2%) of group B patients. Postoperative complications were reported in 5 (29.4%) and 4 (28.6%) patients in groups A and B, respectively. Notably, 1 patient from group A developed grade ≥3 acute renal failure and 1 from group B experienced grade ≥3 pleural effusion requiring drainage. Grade ≥3 TEAEs occurred in 25.0% patients from group A and 40.0% from group B. Conclusions:In resectable LA-ESCC patients, neoadjuvant camrelizumab and cisplatin combined with paclitaxel or albumin-bound paclitaxel was well tolerated and showed promising anti-tumor activity. Citation Format: Zhihao Lu, Yanshuo Cao, Liang Dai, Fengxiao Dong, Lin Shen. Camrelizumab plus chemotherapy as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): A single-center, randomized, phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT209.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

MRI-based tumor shrinkage patterns after early neoadjuvant therapy in breast cancer: correlation with molecular subtypes and pathological response after therapy

BackgroundMRI-based tumor shrinkage patterns (TSP) after neoadjuvant therapy (NAT) have been associated with pathological response. However, the understanding of TSP after early NAT remains limited. We aimed to analyze the relationship between TSP after early NAT and pathological response after therapy in different molecular subtypes.MethodsWe prospectively enrolled participants with invasive ductal breast cancers who received NAT and performed pretreatment DCE-MRI from September 2020 to August 2022. Early-stage MRIs were performed after the first (1st-MRI) and/or second (2nd-MRI) cycle of NAT. Tumor shrinkage patterns were categorized into four groups: concentric shrinkage, diffuse decrease (DD), decrease of intensity only (DIO), and stable disease (SD). Logistic regression analysis was performed to identify independent variables associated with pathologic complete response (pCR), and stratified analysis according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype.Results344 participants (mean age: 50 years, 113/345 [33%] pCR) with 345 tumors (1 bilateral) had evaluable 1st-MRI or 2nd-MRI to comprise the primary analysis cohort, of which 244 participants with 245 tumors had evaluable 1st-MRI (82/245 [33%] pCR) and 206 participants with 207 tumors had evaluable 2nd-MRI (69/207 [33%] pCR) to comprise the 1st- and 2nd-timepoint subgroup analysis cohorts, respectively. In the primary analysis, multivariate analysis showed that early DD pattern (OR = 12.08; 95% CI 3.34–43.75; p < 0.001) predicted pCR independently of the change in tumor size (OR = 1.37; 95% CI 0.94–2.01; p = 0.106) in HR+/HER2− subtype, and the change in tumor size was a strong pCR predictor in HER2+ (OR = 1.61; 95% CI 1.22–2.13; p = 0.001) and triple-negative breast cancer (TNBC, OR = 1.61; 95% CI 1.22–2.11; p = 0.001). Compared with the change in tumor size, the SD pattern achieved a higher negative predictive value in HER2+ and TNBC. The statistical significance of complete 1st-timepoint subgroup analysis was consistent with the primary analysis.ConclusionThe diffuse decrease pattern in HR+/HER2− subtype and stable disease in HER2+ and TNBC after early NAT could serve as additional straightforward and comprehensible indicators of treatment response.Trial registration: Trial registration at https://www.chictr.org.cn/. Registration number: ChiCTR2000038578, registered September 24, 2020.

Peripheral T lymphocyte and immunocyte subset dynamics: markers of neoadjuvant therapy outcomes in esophageal squamous cell carcinoma.

In patients with resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy increased the curative resection rate, disease-free survival, and overall survival for patients with resectable ESCC. However, the efficacy of neoadjuvant therapy varies among different patients. We aim to compare the differences in the characteristics of peripheral blood T lymphocyte subsets before and after neoadjuvant therapy in patients with different curative efficacy. This study enrolled 266 ESCC patients who received neoadjuvant therapy and esophagectomy from August 2018 to August 2022. The postoperative pathological results divided patients into the major pathological response (MPR) and non-MPR groups. Compare the differences in peripheral blood T lymphocyte subsets and analyze the trend of changes in T lymphocyte subsets at different phases of treatment. Propensity score matching was used to reduce the influence of potential confounding factors. Prior to the neoadjuvant therapy, particularly before the second cycle, the MPR group exhibited significantly higher ratios of CD4/CD8 (P=0.009) and helper T cells (TH ratio, P=0.030) compared to the non-MPR group. In contrast, the suppressor T cell ratio (TS ratio) was lower (P=0.016) in the MPR group. The difference in peripheral blood lymphocyte subsets between the two groups of patients who underwent neoadjuvant chemoradiotherapy is significant. In peripheral blood, T lymphocyte subsets varied significantly based on the effectiveness of neoadjuvant treatment. Prior to the second cycle of neoadjuvant therapy, a higher CD4/CD8 and TH ratio, coupled with a decreased TS ratio, might suggest enhanced treatment outcomes.

Neoadjuvant sintilimab plus chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: a prospective, single-arm, phase II clinical trial (CY-NICE).

Adding immune checkpoint inhibitors (ICIs) to the chemotherapy has shown significant clinical benefits in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Sintilimab is one such ICI used for treatment. Herein, we designed a trial to evaluate the safety and efficacy of sintilimab combined with paclitaxel and platinum for locally advanced resectable ESCC. Patients with locally advanced resectable (stage II-III) ESCC were enrolled and received at least two cycles of neoadjuvant therapy with sintilimab (200 mg on day 1) plus platinum-based chemotherapy in each 3-week cycle followed by esophagectomy. The primary endpoint of the trial was the pathological complete response (pCR) rate. The secondary endpoints were the major pathological response (MPR) rate, the objective response rate (ORR), the treatment-related adverse events (TRAEs), the immune-related adverse events (irAEs) and quality of life (QOL). Besides, relapse-free survival (RFS), overall survival (OS) were exploratory endpoints. Forty-three cases were needed to be enrolled in this trial. It was assumed the regimen of the neoadjuvant sintilimab plus chemotherapy would achieve a pCR rate of 30.5%. Between March 2021 and January 2023, a total of 43 patients (41 men and 2 women) were enrolled, including 11 cases (25.6%) of clinical stage II and 32 cases (74.4%) of clinical stage III at baseline. All the 43 patients completed two cycles of neoadjuvant therapy, and 32 patients received McKeown radical resection for esophageal cancer. The pCR rate was 28.1% (9/32), which was below the 30.5% reference cutoff value, and the MPR rate was 37.5% (12/32). According to RECIST 1.1, four patients (4/43, 9.3%) had a complete response (CR), 21 patients (21/43, 48.8%) had a partial response (PR), ORR was 58.1% (25/43). The incidence of ≥ grade 3 TRAEs was 23.3% (10/43) and there were no ≥ grade 4 TRAEs. Sintilimab plus platinum-based chemotherapy as neoadjuvant therapy is safe, feasible and effective in locally advanced resectable ESCC, suggesting a supportive rationale for its further evaluation in randomized clinical trials. Chinese Clinical Trial Registry identifier: ChiCTR2200056558.

The efficacy and feasibility of neoadjuvant immunotherapy plus chemotherapy followed by McKeown minimally invasive oesophagectomy for locally advanced oesophageal squamous cell carcinoma.

In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

Neoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in resectable non-small cell lung cancer

BackgroundNeoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC. MethodsThis was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed. ResultsOf the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS <50% and ≥50% (all P > 0.05). ConclusionNeoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.

Treg cells and the response to neoadjuvant chemotherapy combined with immunotherapy in resectable esophageal squamous carcinoma.

e14626 Background: More and more studies focus on the neoadjuvant chemotherapy combined with immunotherapy (chemo-immunotherapy) in resectable esophageal squamous carcinoma (ESCC). Herein, we aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death protein 1 inhibitors with chemotherapy and explore tumor microenvironment (TME) profiles. Methods: Patients with previously untreated, resectable, stage III ESCC in the third affiliated hospital of Soochow University were enrolled. Each patient received two-four cycles of neoadjuvant chemo-immunotherapy before surgical resection. The TME profiles of formalin-fixed paraffin-embedded tumor samples at baseline were evaluated by multiplex immunofluorescence to discover novel biomarkers of response to neoadjuvant chemo-immunotherapy. Results: Twenty patients were included, all of whom underwent R0 resection. 85% (17/20) of patients underwent 2 cycles of neoadjuvant therapy. TP53 (13/20,65%) was were high-frequency mutated gene, followed by CDKN2A (5/20,25.0%) and PIK3CA (3/20, 15.0%). PD-L1 positive (TPS≥1%) was found in only 3 patients. Postoperative pathological evaluation showed that 18 patients (90.0%) were major pathologic response (MPR), of which 5 patients (28.0%) achieved pathological complete response (pCR). Neoadjuvant therapy has acceptable side effects. TME profiles at baseline showed no significant correlation between PD-L1 and pathological response. The density of Treg cell in the tumor area was significantly lower in pCR patients than in MPR patients (P=0.0302). Conclusions: Neoadjuvant chemo-immunotherapy was well tolerated and was effective therapy for resectable ESCC. Treg cells may serve as potential predictive biomarkers.

A phase II study of toripalimab combined with gemcitabine-cisplatin as neoadjuvant therapy for patients with muscle-invasive bladder cancer (MIBC).

e16602 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care in MIBC with improved pathologic response (PaR) and overall survival (OS) compared to radical cystectomy (RC) alone. The efficacy of PD-1 inhibitor in combination with chemotherapy as a new neoadjuvant treatment option for MIBC still needs further confirmation. This study evaluated the efficacy and safety of toripalimab (an anti-PD-1 monoclonal antibody) combined with gemcitabine-cisplatin (GC) as neoadjuvant therapy for patients with MIBC. Methods: Eligible pts with MIBC (cT2-T4a, N≤1, M0) who were candidates for RC were enrolled. Toripalimab (240mg, d1) combined with GC (gemcitabine 1000mg/m2 d1,d8 plus cisplatin 35mg/m2 d1,d2) every 21 days, up to 4 cycles. RC was performed within 6 weeks after the last dose treatment. The primary endpoint was PaR (≤ pT1,N0). Secondary endpoints were PFS at 2 years and safety. Results: Between Apr 2021 and Jun 2022, 16 pts (4 pts cT2, 11 pts cT3, 1 pts cT4) were enrolled and received 4 cycles of neoadjuvant therapy, with median age of 63.5 and 75% male. 14 of the 16 pts underwent RC and two declined RC. Among 14 evaluable pts, PaR ≤pT1N0 was achieved in 12 pts (85.71%, 4 were pT0, 8 were pT1/a/is). Survival data are not yet mature. The most common adverse events (AEs) of any grade were anemia (14/16; 87.5%) and nausea/vomiting (11/16; 68.75%). One had Grade≥3 AEs (hemorrhagic shock) while on study that was unrelated to GC or toripalimab. Five pts experienced grade 1-2 immune related AEs, including thyroiditis (3/16, 18.75%) and rash (2/16,12.5%). Conclusions: Neoadjuvant toripalimab combined with GC showed promising safety and efficacy in MIBC with significant pathologic downstaging rates. Clinical trial information: NCT04861584 .

Anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome, and nedaplatin regimen for preoperative neoadjuvant therapy of esophageal cancer: A single-arm, single-center, phase II exploratory clinical study.

e16082 Background: Local recurrence and distant metastasis are important causes of high mortality in patients with locally advanced esophageal cancer. Neoadjuvant therapy combined with surgery can significantly improve the prognosis of patients with locally advanced esophageal cancer. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitors) and tislelizumab (anti-pd-1 antibodies), paclitaxel liposome (a cytotoxic anti-tumor drugs) and nedaplatin (a platinum-based anti-tumor drugs) in patients with esophageal cancer, to evaluate the efficacy and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin in preoperative neoadjuvant therapy for patients with stage IIB-IVA esophageal cancer. Methods: This study included 18-75 years old, ECOG PS 0-1 patients with potentially resectable stage IIB-IVA esophageal cancer with a predicted survival time of ≥12 weeks and confirmed by histopathology or cytology. Patients who met the inclusion criteria received anlotinib (oral, 12mg/d1-14,Q3W) combined with tislelizumab (intravenous drip, 200mg/d1,Q3W), paclitaxel liposome (intravenous drip, 175mg/m2/d1,Q3W) and nedaplatin (intravenous drip, 80mg/m2/d1,Q3W). After 2 cycles of neoadjuvant therapy, surgery was performed, and 4-6 weeks of chemotherapy combined with targeted immune adjuvant therapy was performed after the operation, and then Anlotinib combined with tislelizumab targeted immune maintenance therapy was performed until the disease progressed. Subjects who failed to complete at least one cycle of clinical trials according to this program due to non-experimental drug factors, and seriously violated this research program, such as: failure to follow the prescribed dose, method and course of medication, will be excluded from this study. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), R0 resection rate, and pathological complete response rate. Results: From October 2021 to February 2023, 38 patients were included in this study, and clinical data of 27 patients can be used to track and evaluate clinical efficacy. The median age of the subjects was 58.5 years (range 47-75 years). the primary study end point was an ORR of 77.8% (95% CI，61%-94.5%). Conclusions: We will strictly implement the research protocol and objectively evaluate the anti-tumor activity and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin regimen in the treatment of patients with stage IIB ~ IVA esophageal cancer. In order to provide a safe and reliable neoadjuvant therapy for patients with locally advanced esophageal cancer. Clinical trial information: ChiCTR2100049693 .

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: A single-arm, phase II trial.

e18072 Background: Previous studies confirmed locally advanced oral or oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients (pts) with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 (PD-1) mAb tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy/chemoradiotherapy in LA OSCC or OPSCC. Methods: In this phase II, single-arm study, eligible pts aged 18-80 diagnosed with stage III-IV (AJCC v8) resectable or potentially resectable LA OSCC or OPSCC received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (60-75 mg/m2) Q3W for 2 cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. The primary endpoint was major pathologic response (MPR). Secondary endpoints included pathological complete response (pCR), objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Thirty-one pts were enrolled from Mar 2022 to Nov 2022, and completed neoadjuvant therapy, with an ORR of 61.3% (19/31) and CR rate of 6.5% (2/31). Of the 31 pts, 29 pts (18 OSCC, 13 OPSCC) successfully underwent surgery with a median age of 57 (34-72) yrs, smoking history 75.9%, alcohol history 72.4% and 82.8% of male. The clinical stage III, IVA and IVB accounted for 24.1%, 48.3% and 27.6%, respectively. The MPR rate was 65.5% (19/29), of which the pCR rate was 41.4% (12/29). R0 resection rate reached 100%. For the per-protocol population, 58.6% pts (17/29) complaint of symptoms included pain, trismus, dysphagic, and speech disorders, all of them reached remission after 2 cycles of neoadjuvant therapy. No delay of surgery occurred. Grade 3-4 adverse events (AEs) occurred in 3 pts including 3.4% G3 leukopenia, 6.9% G3 anemia and 3.4% G4 thrombocytopenia and mostly chemotherapy related. Grade 1-2 AEs included 13.8% anemia, 3.4% thrombocytopenia, 17.2% leukopenia, 13.8% increased aminotransferase, 3.4% increased creatinine, 3.4% hyperglycemia, 27.6% anorexia, 3.4% vomiting, 3.4% diarrhea, 10.3% constipation, 6.9% rash, 100% alopecia and 17.2% fatigue. Conclusions: Neoadjuvant tislelizumab combined with chemotherapy yielded promising MPR and pCR rates with an acceptable safety profile in LA OSCC or OPSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200056354 .

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]

Neoadjuvant tislelizumab combined with APF for patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial.

6080 Background: Seeking out a more effective and less-toxic regimen is necessary for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The aim of this study is to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death-1 antibody tislelizumab combined with APF (albumin-bound paclitaxel, platinum and fluorouracil) followed by surgery or concurrent chemoradiotherapy. Methods: In this prospective, single-center, single-arm clinical study, previously untreated patients with locally advanced HNSCC, aged 18-75 years without severe comorbidities and contraindications to immunotherapy are enrolled. Eligible patients received A (200 mg/m2 d1) P (60 mg/m2 d1- d2) F (600 mg/m2 CIV120h) induction chemotherapy along with tislelizumab (200 mg d1) every 3 weeks. The curative effect is evaluated (RECIST 1.1) after 3 cycles and a multidisciplinary team discuss whether to perform surgery. For patients undergoing surgery, treatment is completed if there is no residual and extra-capsular lymph node invasion; in case of positive surgical margin, or extracapsular lymph node invasion, or residual lymph nodes, patient will receive concurrent chemoradiotherapy (tumor bed and neck lymph drainage area 66 Gy~70 Gy, P 60 mg/m2). Those not suitable for surgery will receive radical concurrent chemoradiotherapy (GTV 66Gy~70Gy, PTV 50Gy, P 60 mg/m2) within 3 weeks after neoadjuvant treatment. The primary endpoint of efficacy evaluation is the pathological complete response (pCR) rate. Safety evaluation indicators include vital signs, laboratory indicators and adverse events (NCI CTC AE4.0). Results: From Apr 2022 to Jan 2023, 12 patients are screened and enrolled. For the 7 patients who complete 3 cycles of neoadjuvant therapy, 3 patients (42.8%) successfully undergo surgery, with 2 patients (28.5%) achieving pCR and 1 patient (14.3%) achieving major pathological response (MPR). For the other 4 patients, 1 patient (14.3%) achieve pCR by multipoint biopsy of the primary lesion and 2 patients (28.5%) obtain radiologic partial response (PR) by MRI. 1 patient’ lymph nodes tend to increase during radiotherapy and that patient withdraw from clinical trial and undergo salvage surgery. The objective response rate (ORR) of neoadjuvant treatment is 85.7% and pCR rate is 42.9%. Grade 2 or higher AEs during neoadjuvant therapy include grade 2 liver function damage (n = 1, 8.3%), grade 3 myelosuppression (n = 1, 8.3%). 1 (8.3%) patient developed radiation-related oral mucositis (RTOG 2). No other obvious adverse reactions of radiotherapy, chemotherapy or immunotherapy are observed. Conclusions: Combining Tislelizumab with APF followed by surgery or radical concurrent chemoradiotherapy is feasible and effective in patients with locally advanced HNSCC, and further studies are needed to verify its effectiveness and safety.

Neoadjuvant tislelizumab plus nab-paclitaxel and carboplatin followed by adjuvant tislelizumab in patients with early triple-negative breast cancer.

602 Background: Triple-negative breast cancer (TNBC) is the subtype with the least favorable outcomes. However, TNBC is associated with higher immune cell abundance than other subtypes, making it a good candidate for immunotherapy. Neoadjuvant chemotherapy is the preferred treatment approach for early TNBC. Emerging evidence shows that additional immune checkpoint inhibitors (ICI) in neoadjuvant therapy significantly increases pathological complete response (pCR) and event-free survival in early TNBC. Treatment regimens of paclitaxel and carboplatin (TP) is class I recommendation for TNBC neoadjuvant therapy, the application of ICI with TP regimens is worth exploring. Methods: In this multicenter, open-label, phase II study, patients with untreated, histologically confirmed TNBC in stage II-III (per AJCC 8th edition) were enrolled. Patients received six cycles of neoadjuvant therapy with tislelizumab at 200 mg once every 3 weeks plus nab-paclitaxel (125 mg/m2 on days 1 and 8) and carboplatin (at a dose based on an area under the concentration 2 on days 1 and 8) every 3 weeks. Patients who either completed or discontinued the neoadjuvant treatment would undergo definitive surgery. After surgery, the patients received adjuvant tislelizumab every 3 weeks for up to 12 cycles. The primary endpoint was the rate of pCR (ypT0/Tis ypN0). The secondary endpoints included 1-, 2-, 3-year event free survival rates and overall survival rates. Based on the Simon’s Two-Stage design, if &gt; 13 of 32 patients achieved pCR, the enrollment would proceed to full accrual of 62 patients as planned. If &gt; 29 of 62 patients achieved pCR, we would deem the study to have met the primary endpoint. Results: From Mar 2021 to Jan 2022, 32 patients were enrolled; 18 of them achieved pCR, and therefore the study proceeded to complete the enrollment of 62 patients. At the data cut-off of Oct 13, 2022, 62 patients were enrolled, among which 50 patients received neoadjuvant treatment and underwent definitive surgery. The median age was 50 years. 36 (72.0%) patients had stage II breast cancer at diagnosis. 31 of the 50 patients achieved pCR (ypT0/Tis ypN0), and the pCR rate was 62.0% (95% CI, 47.2-75.4). Patients with immune cell PD-L1 expression ≥10% had numerically higher pCR rate (81.8% vs 53.6%) than those with PD-L1 expression ≥1%. All 50 (100%) patients reported any grade of neoadjuvant treatment-related adverse events (TRAEs). Grade ≥3 TRAEs occurred in 27 (54%) patients. The rate of immune-related adverse events (irAEs) was 34% (17/50), with the common occurring (10%) irAE of hypothyroidism (n = 8, 16%). 2 (4.9%) patients experienced grade ≥3 irAEs. Severe adverse events were reported in 5 (10%) patients. Conclusions: The study has met its primary endpoint. Tislelizumab plus nab-paclitaxel and carboplatin achieved a higher pCR and was generally well tolerated in the neoadjuvant treatment of early TNBC. Clinical trial information: ChiCTR2100041675 .

Early Circulating Tumor DNA Dynamics Predict Neoadjuvant Therapy Response and Recurrence in Colorectal Liver Metastases: A Prospective Study.

For patients with colorectal liver metastases (CRLM) who receive neoadjuvant therapy (NAT), reliable indicators that can early and accurately predict treatment response are lacking. This study was conducted to prospectively investigate the potential of early circulating tumor DNA (ctDNA) dynamics as a precise predictor of NAT response and recurrence in CRLM. This study prospectively enrolled 34 patients with CRLM who received NAT, with blood samples collected and subjected to deep targeted panel sequencing at two time points: 1 day before the first and the second cycles of NAT. Correlations of ctDNA mean variant allele frequency (mVAF) dynamics and treatment response were assessed. The performance of early ctDNA dynamics in predicting treatment response was assessed and compared with those of carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). The baseline ctDNA mVAF was significantly associated with pre-NAT tumor diameter (r = 0.65; P < 0.0001). After one cycle of NAT, the ctDNA mVAF declined remarkably (P < 0.0001). The dynamic change in ctDNA mVAF of 50% or more was significantly correlated with better NAT responses. The discriminatory capacity of ctDNA mVAF changes was superior to that of CEA or CA19-9 in predicting radiologic response (area under the curve [AUC], 0.90 vs 0.71 vs 0.61) and pathologic tumor regression grade (AUC, 0.83 vs 0.64 vs 0.67). The early changes in ctDNA mVAF but not CEA or CA19-9 were an independent indicator of recurrence-free survival (RFS) (hazard ratio, 4.0; P = 0.023). For CRLM patients receiving NAT, an early ctDNA change is a superior predictor of treatment response and recurrence compared with conventional tumor markers.

Radiomics Based on DCE-MRI for Predicting Response to Neoadjuvant Therapy in Breast Cancer

To compare the value of radiomics and diameter% based on pre- and early-treatment dynamic enhanced MR (DCE-MRI) of the breast in predicting response to neoadjuvant therapy (NAT) in breast cancer and to construct a tool for early noninvasive prediction of NAT outcomes. Retrospective analysis of clinical and imaging data of 142 patients with primary invasive breast cancer who underwent DCE-MRI before and after two cycles of NAT at our institution. Enroled patients were randomly assigned in a 7:3 ratio to the training group and the test group. Patients were divided into pathological complete response (pCR) and non-pathological complete response groups based on surgical pathology findings after NAT. The maximum diameter relative regression values (Diameter%) before and after treatment were calculated and the conventional imaging Diameter% model was constructed. Based on pre- and early-NAT DCE-MRI, the optimal features of pre-NAT, early-NAT, and delta radiomics were screened using redundancy analysis, least absolute shrinkage, and selection operator methods to construct the corresponding radiomics model and calculate the Radscores. Indicators that were statistically significant in the univariate analysis of clinical data were further screened by stepwise regression and combined with Radscores to construct the fusion model. All models were evaluated and compared. In the test set, the area under the curve (AUC) of the delta radiomics model (0.87) was higher than that of the pre-NAT, early-NAT radiomics models (0.57, 0.78) and the Diameter% model (0.83). The fusion model had the best efficacy in predicting pCR after NAT, with AUCs of 0.91 in the training and test sets. And its nomogram plot showed that Radscore of early-NAT radiomics had the greatest weight. In the test set, the fusion model and Delta radiomics model improved the efficacy of predicting pCR by 35.56% and 14.19%, respectively, compared to the Diameter% model (P=0 and .039). Clinical decision curves showed the highest overall clinical benefit for the fusion model. Radiomics, especially delta and early-NAT radiomics, may be potential biomarkers for early noninvasive prediction of NAT outcomes. And a fusion model constructed from meaningful clinicopathological indicators combined with radiomics can effectively predict NAT response.