Early Triple-negative Breast Cancer Research Articles

Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial

ObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres...

Delivery of IL2RG mRNA via nanoparticles to enhance CD8+ T cell promotes anti-tumor effects against late-stage triple-negative breast cancer

BackgroundThe manipulation of CD8+ T cell functions through genetic modifications presents a novel approach to cancer immunotherapy. This study aimed to explore the effects of IL2RG-overexpressing CD8+ T cells and assess the efficacy of delivering IL2RG mRNA via nanoparticles (NPs) to the tumor microenvironment in triple-negative breast cancer (TNBC).MethodsSingle-cell RNA sequencing (scRNA-seq) was conducted on tissue from early and late-stage TNBC, followed by a meta-analysis of six breast cancer arrays from the GEO database to identify candidate genes. CRISPR/Cas9 was employed for gene knockout and overexpression in CD8+ T cells, which were then analyzed using flow cytometry, ELISA, immunofluorescence, and metabolic assays. A 3D cancer cell spheroid model was used for co-culture experiments. Lipid-coated calcium-phosphate (LCP)@IL2RG NPs were synthesized and injected into TNBC mouse models.ResultsIL2RG was identified as significantly associated with late-stage TNBC. Overexpression of IL2RG in CD8+ T cells led to increased cell activation, cytotoxicity, and glycolysis, while knockout reduced these effects. Overexpressing IL2RG in CD8+ T cells co-cultured with 3D cancer spheroids resulted in enhanced apoptosis and reduced cancer cell invasion. Injection of LCP@IL2RG NPs into TNBC mouse models significantly mitigated tumor growth.ConclusionsOverexpressing IL2RG in CD8+ T cells enhances tumor immunotherapy. Delivering IL2RG mRNA via NPs further amplifies this effect, offering a promising strategy for the treatment of late-stage TNBC.

Real-World Immune-Related Adverse Events in Patients With Early Triple-Negative Breast Cancer Who Received Pembrolizumab.

The addition of pembrolizumab to chemotherapy in high-risk early triple-negative breast cancer (TNBC) improves cancer outcomes. However, pembrolizumab induces varied immune-related adverse events (irAEs) where some can be severe or lifelong. This retrospective study describes real-world patterns of irAEs in patients with TNBC who received pembrolizumab. We evaluated irAEs in patients with TNBC from a comprehensive cancer center and a community hospital who received pembrolizumab with chemotherapy between 2021 and 2023, excluding those enrolled in clinical trials. We used national guidelines to grade toxicities. Logistic regression assessed the effect of clinicopathologic variables on irAEs adjusting for covariates. We identified 233 patients with a median age of 51 years, 62% had stage II TNBC, 35% had stage III TNBC, 25% were Hispanic, 21% were Black, and 42% were White. Eighty patients (34%) developed 100 separate irAEs. The most common irAEs were endocrinopathies (52%) and GI (23%); there were 26 grade ≥3 irAEs, which all resulted in hospitalization, the most common being GI (13 instances); 45 required systemic steroids, 16 required additional immunosuppressive therapy, and 32 patients discontinued pembrolizumab because of irAEs. Two patients who developed colitis eventually died due to complications. Most (67 instances) irAEs were unresolved at the time of last follow-up, but 55% (37/67) had improved to grade 1. No clinicopathologic factors were associated with the development or severity of irAEs. In this real-world diverse population, we observed rates of irAEs comparable with KEYNOTE-522, where endocrinopathies were the most prevalent, but GI irAEs were also prevalent and severe. This emphasizes a critical issue as pembrolizumab is increasingly being used in early TNBC and could have long-term survivorship implications.

The prognostic impact of Her2 status in early triple negative breast cancer: a Turkish Oncology Group (TOG) study

The studies evaluating the impact of Her2 levels in neoadjuvant setting have conflicting data. The aim of the study was to evaluate the prognostic impact of Her2 status in early triple negative breast cancer(TNBC). In the study TNBC patients who were treated with neoadjuvant chemotherapy (NAC) and surgery were analyzed retrospectively. The primary aim of the study was to analyze the impact of Her2 status(Her2-0 and Her2-low) on pathological complete response (pCR). The secondary objectives were disease free survival (DFS) and overall survival (OS). 620 female triple negative breast cancer patients were evaluated. 427 patients (68.9%) had Her2-0 and 193(31.1%) had her2-low pathology. The pCR rates were similar between Her2-0 and Her2-low patients (33.0% vs. 27.5%, p = 0.098). Although Her2-0 group has better DFS (106 vs. 50 months, p = 0.002), in multivariate analysis it had a HR of 0.74 (p = 0.06). In addition, OS was similar (131 vs. 105 months, p = 0.13) with a HR of 0.88 (p = 0.61). In multivariate analysis; presence of LVI (HR:2.2 (95% CI 1.1–3.5) p = 0.001), Clinical stage T1/T2 (HR:0.39 (95% CI 0.2–0.6) p < 0.001) and lymph node negativity (HR:0.35 (95% CI 0.1–0.9) p = 0.03) were independent factors for OS. Although there were pathological and clinical differences, the pCR, DFS and OS were similar between Her2-0 and Her2-low TNBC patients. The importance of Her2 status of TNBC in neoadjuvant setting should be further studied.

P87-9 Effect of pembrolizumab as neoadjuvant therapy in early triple-negative breast cancer: a systematic review

P87-9 Effect of pembrolizumab as neoadjuvant therapy in early triple-negative breast cancer: a systematic review

Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy.

Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum-based neoadjuvant treatment. We prospectively enrolled women with stage IIB-IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline-based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease-free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled. The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3-year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS. Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.

Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.

Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II-III triple-negative breast cancer; however, it is largely unknown for which patients ICI without chemotherapy could be an option and what the benefit of combination ICI could be. The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary end point, twofold increase in CD8+ T cells or IFNG), providing a rationale for neoadjuvant ICI without chemotherapy. Here, in window-of-opportunity cohorts A (4 weeks of anti-PD-1) and B (4 weeks of anti-PD-1 + anti-CTLA4), we observed immune activation in 53% (8 of 15) and 60% (9 of 15) of patients, respectively. High levels of tumor-infiltrating lymphocytes correlated with response. Single-cell RNA sequencing revealed that higher pretreatment tumor-reactive CD8+ T cells, follicular helper T cells and shorter distances between tumor and CD8+ T cells correlated with response. Higher levels of regulatory T cells after treatment were associated with nonresponse. Based on these data, we opened cohort C for patients with high levels of tumor-infiltrating lymphocytes (≥50%) who received 6 weeks of neoadjuvant anti-PD-1 + anti-CTLA4 followed by surgery (primary end point, pathological complete response). Overall, 53% (8 of 15) of patients had a major pathological response (<10% viable tumor) at resection, with 33% (5 of 15) having a pathological complete response. All cohorts met Simon's two-stage threshold for expansion to stage II. We observed grade ≥3 adverse events for 17% of patients and a high rate (57%) of immune-mediated endocrinopathies. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early triple-negative breast cancer. ClinicalTrials.gov registration: NCT03815890 .

Three-dimensional analysis of mitochondria in a patient-derived xenograft model of triple negative breast cancer reveals mitochondrial network remodeling following chemotherapy treatments.

Mitochondria are hubs of metabolism and signaling and play an important role in tumorigenesis, therapeutic resistance, and metastasis in many cancer types. Various laboratory models of cancer demonstrate the extraordinary dynamics of mitochondrial structure, but little is known about the role of mitochondrial structure in resistance to anticancer therapy. We previously demonstrated the importance of mitochondrial structure and oxidative phosphorylation in the survival of chemotherapy-refractory triple negative breast cancer (TNBC) cells. As TNBC is a highly aggressive breast cancer subtype with few targeted therapy options, conventional chemotherapies remain the backbone of early TNBC treatment. Unfortunately, approximately 45% of TNBC patients retain substantial residual tumor burden following chemotherapy, associated with abysmal prognoses. Using an orthotopic patient-derived xenograft mouse model of human TNBC, we compared mitochondrial structures between treatment-naïve tumors and residual tumors after conventional chemotherapeutics were administered singly or in combination. We reconstructed 1,750 mitochondria in three dimensions from serial block-face scanning electron micrographs, providing unprecedented insights into the complexity and intra-tumoral heterogeneity of mitochondria in TNBC. Following exposure to carboplatin or docetaxel given individually, residual tumor mitochondria exhibited significant increases in mitochondrial complexity index, area, volume, perimeter, width, and length relative to treatment-naïve tumor mitochondria. In contrast, residual tumors exposed to those chemotherapies given in combination exhibited diminished mitochondrial structure changes. Further, we document extensive intra-tumoral heterogeneity of mitochondrial structure, especially prior to chemotherapeutic exposure. These results highlight the potential for structure-based monitoring of chemotherapeutic responses and reveal potential molecular mechanisms that underlie chemotherapeutic resistance in TNBC.

Mass Spectrometry-Based Proteomics for Classification and Treatment Optimisation of Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) presents a significant medical challenge due to its highly invasive nature, high rate of metastasis, and lack of drug-targetable receptors, which together lead to poor prognosis and limited treatment options. The traditional treatment guidelines for early TNBC are based on a multimodal approach integrating chemotherapy, surgery, and radiation and are associated with low overall survival and high relapse rates. Therefore, the approach to treating early TNBC has shifted towards neoadjuvant treatment (NAC), given to the patient before surgery and which aims to reduce tumour size, reduce the risk of recurrence, and improve the pathological complete response (pCR) rate. However, recent studies have shown that NAC is associated with only 30% of patients achieving pCR. Thus, novel predictive biomarkers are essential if treatment decisions are to be optimised and chemotherapy toxicities minimised. Given the heterogeneity of TNBC, mass spectrometry-based proteomics technologies offer valuable tools for the discovery of targetable biomarkers for prognosis and prediction of toxicity. These biomarkers can serve as critical targets for therapeutic intervention. This review aims to provide a comprehensive overview of TNBC diagnosis and treatment, highlighting the need for a new approach. Specifically, it highlights how mass spectrometry-based can address key unmet clinical needs by identifying novel protein biomarkers to distinguish and early prognostication between TNBC patient groups who are being treated with NAC. By integrating proteomic insights, we anticipate enhanced treatment personalisation, improved clinical outcomes, and ultimately, increased survival rates for TNBC patients.

Can we counterbalance restricted access to innovation through specialized breast cancer care? The REAL-NOTE study

IntroductionThe KEYNOTE-522 (KN-522) trial showed that the addition of pembrolizumab to standard chemotherapy improved pathological complete response (pCR) and event-free survival (EFS) for patients with early triple negative breast cancer (TNBC). We analyzed results of a real-world cohort of patients treated in a certified Breast Unit, before the introduction of pembrolizumab, to see if high quality care can match outcomes brought by the addition of an innovative anticancer therapy. MethodsObservational, retrospective, single-center cohort study, with real-world data from an ongoing institutional database with prespecified variables. Inclusion criteria matched the ones from KN-522: previously untreated stage II or III TNBC, diagnosed between 2012 and 2022, who received neoadjuvant chemotherapy. The primary endpoints were pCR at the time of definitive surgery and EFS; overall survival (OS) was a secondary endpoint. ResultsTotal of 168 patients were included, median age 55 years, 55 % received neoadjuvant chemotherapy with dose dense anthracyclines and taxanes and 25 % carboplatin + paclitaxel, sequenced with dose dense anthracyclines. Most had Stage II disease (82.7 %), 47 % node + disease. pCR was achieved in 52.7 % cases. At 36 months, EFS was 83.3 % (95 % CI 75.1–89.0) and OS 89 % (95 % CI, 81.6 to 93.5). ConclusionsNotwithstanding the study limitations, outcomes of patients treated with chemotherapy without immunotherapy were numerically similar to the experimental arm of KN-522 trial. These data highlight that providing care by a specialized multidisciplinary team in a certified unit might be just as impactful as the incorporation of new technologies.

269P Her2-low/HRR proficient early triple negative breast cancer is characterized by good prognosis

269P Her2-low/HRR proficient early triple negative breast cancer is characterized by good prognosis

238MO PROMENADE: PembROlizuMab for early triple negative ER-low breast caNcer, reAl worlD frEnch cohort

238MO PROMENADE: PembROlizuMab for early triple negative ER-low breast caNcer, reAl worlD frEnch cohort

Towards targeting the breast cancer immune microenvironment.

The tumour immune microenvironment is shaped by the crosstalk between cancer cells, immune cells, fibroblasts, endothelial cells and other stromal components. Although the immune tumour microenvironment (TME) serves as a source of therapeutic targets, itis also considered a friend or foe to tumour-directed therapies. This is readily illustrated by the importance of T cells in triple-negative breast cancer (TNBC), culminating in the advent of immune checkpoint therapy in combination with cytotoxic chemotherapy as standard of care for both early and advanced-stage TNBC, as well as recent promising signs of efficacy in a subset of hormone receptor-positive disease. In this Review, we discuss the various components of the immune TME in breast cancer and therapies that target or impact the immune TME, as well as the complexity of host physiology.

Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer.

The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

Empowerment, Pain Control, and Quality of Life Improvement in Early Triple-Negative Breast Cancer Patients through Pain Neuroscience Education: A Prospective Cohort Pilot Study Protocol (EMPOWER Trial).

The treatment of early triple-negative breast cancer (eTNBC) has improved patients' prognosis but often leads to adverse events and sequelae affecting quality of life (QoL). Pain Neuroscience Education (PNE) is a promising non-pharmacological intervention in this field. Preliminary data have shown the beneficial effect of PNE in BC survivors. However, there are still gaps in knowledge regarding its optimal use in eTNBC. To address this issue, a prospective pilot study will enroll 30 consecutive patients diagnosed with eTNBC at IRCCS Humanitas Research Hospital. The PNE program will consist of 10 weekly sessions to be started within 4 weeks of the onset or worsening of a pain syndrome (PS). QoL, pain, and disability will be assessed before, during, at the end of, and 6 months after PNE using validated questionnaires. Peripheral venous blood samples will be taken before and at the end of PNE to evaluate inflammatory serum biomarker levels. The primary objective is to evaluate whether PNE leads to clinical improvement in QoL and pain. If successful, it will be validated in a larger multi-centric cohort, potentially leading to its widespread implementation as a standard pain management tool for eTNBC patients.

Unforeseen Complications of Pembrolizumab in Breast Reconstruction Post-Mastectomy.

Among patients with early triple-negative breast cancer, the combination of pembrolizumab with neoadjuvant chemotherapy enhances outcomes compared to chemotherapy alone.Early recognition is essential for managing pembrolizumab-induced complications, as demonstrated by the need for expander removal and debridement in this case.The unique adverse effects observed in this case underscore the importance of tailoring cancer treatment plans to individual patients, taking into account the potential risks associated with immunotherapy in the context of reconstructive surgery.

Neoadjuvant anthracycline followed by toripalimab combined with nab-paclitaxel in patients with early triple-negative breast cancer (NeoTENNIS): a single-arm, phase II study

Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2). Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

A-BRAVE trial: A phase III randomized trial with avelumab in early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk after primary surgery and adjuvant chemotherapy.

LBA500 Background: Prognosis of pts with early triple negative breast cancer (TNBC) is still poor and new effective treatments are needed. TNBC is the most immunogenic BC subtype, and this may account for sensitivity to immune checkpoint inhibitors. The A-BRAVE trial was designed to evaluate the efficacy of avelumab, an anti PD-L1 antibody, as adjuvant treatment for pts with early TNBC at high risk. Methods: This is a phase III, multicentric, randomized adjuvant study comparing 1 year of treatment with the anti PD-L1 avelumab vs observation for TNBC pts considered at high risk of relapse. Pts were enrolled after they completed standard treatment with curative intent including surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as: 1) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (Stratum A), 2) &gt;pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum B). Pts were randomly assigned (1:1, balanced for strata A and B) to Avelumab 10 mg/kg I.V. q2w for 1 year or observation. Co-primary endpoints were disease free survival (DFS) in the total population and in Stratum A. 474 pts were needed to detect, in the total population, an improvement from 60% to 73.6% 3-year DFS rate (HR 0.6; 90% power, 1-sided test, alfa 2%). 172 DFS events were required to perform the event-driven analysis. Assuming a proportion of 70-80% pts enrolled in Stratum A, the expected power to detect an HR 0.6 at alpha allocated in this subgroup is 70-79%. Overall survival was a secondary endpoint. Results: From June 2016 to October 2020, 477 pts were randomly assigned from 64 Italian and 6 UK centers. 11 pts (3 avelumab, 8 control) withdrew consent immediately after randomisation and are excluded from further analyses. 378 pts entered Stratum A (83%), of whom 99 (57 avelumab, 42 control) received further chemotherapy after surgery prior to enrollment in the trial. Efficacy results for the two co-primary DFS endpoints and the secondary OS endpoints are reported in the table. Conclusions: One year adjuvant avelumab versus control does not significantly improve DFS in high-risk TNBC patients. Nevertheless, the secondary enpoind OS was significanlty improved with avelumab vs control. RFS and DMFS will also be reported. A centralised collection of tumor tissue, plasma and feces has been performed and will allow a number of correlative studies. Clinical trial information: NCT02926196 . [Table: see text]

A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo) adjuvant therapy in patients with early triple-negative breast cancer: Korean Cancer Study Group BR 15-1 PEARLY trial.

LBA502 Background: Triple-negative breast cancer (TNBC) is known for its high risk of early relapse and poor prognosis. Platinum agents have shown to increase pathological complete response (pCR) rates when added to neoadjuvant chemotherapy for TNBC. However, evidence regarding the survival benefit of platinum in this setting remains inconclusive. The PEARLY trial is a multicenter, randomized, open-label, phase 3 study designed to assess the efficacy and safety of carboplatin in combination with anthracycline/taxane therapy compared to standard anthracycline/taxane alone as either neoadjuvant or adjuvant treatment in early-stage TNBC. Methods: Patients with stage II or III TNBC were randomly assigned to either the carboplatin arm or the standard therapy arm, stratified by nodal status, institution, treatment setting (neoadjuvant vs adjuvant), and germline BRCA status. The standard therapy involved doxorubicin and cyclophosphamide (AC) followed by taxane treatment. The experimental arm included carboplatin in addition to taxane following AC. The primary endpoint was event-free survival (EFS), defined as disease progression or inoperable status for neoadjuvant therapy group, local or distant recurrence, occurrence of a second primary cancer, or death from any cause, while secondary endpoints encompassed overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety. With a planned enrollment of 878 patients, the trial aimed for 80% power to detect a hazard ratio of 0.70 for EFS at a two-sided alpha level of 0.05, anticipating 248 EFS events over a 5-year follow-up period. Results: Between Jan 2016 and Jun 2020, 868 patients across 22 institutions in South Korea were enrolled. At a median follow-up of 51.1 months, carboplatin significantly improved EFS compared to the control arm (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.50 to 0.93; p=0.017). The 5-year EFS rates were increased from 74.4% to 81.9%, demonstrating a 7.5% difference. Subgroup analysis showed consistent benefits across various patient categories. Secondary endpoints like IDFS and DRFS also favored carboplatin arm. OS data were immature, a total of 43 patients (10.2%) in the carboplatin arm and 57 patients (13.1%) in the control arm died (HR 0.66; 95% CI: 0.42 to 1.01). Grade ≥3 treatment-related adverse event rates were 74.6% (1 death due to infection) in the carboplatin arm and 56.7% (2 deaths due to infection and suicide) in the control arm. Conclusions: The addition of carboplatin to standard anthracycline followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. The safety profile was consistent with the known expectations for each regimen. Clinical trial information: NCT02441933 .

Real-world immune-related adverse events in patients with early triple negative breast cancer who received pembrolizumab.

1099 Background: The addition of pembrolizumab to chemotherapy (KEYNOTE-522 regimen) in high risk early triple negative breast cancer (TNBC) has improved clinical outcomes. However, this treatment can result in immune-related adverse events (irAEs) involving any organ and in some cases, life-long toxicities or even death. This retrospective study describes real-world patterns of irAEs in patients (pts) with early TNBC who received pembrolizumab at two academic centers. Methods: We evaluated irAEs in pts with stage II-III TNBC from MD Anderson Cancer Center and Lyndon B Johnson diagnosed between January 2018 and May 2023 who received neoadjuvant pembrolizumab plus chemotherapy. We excluded those enrolled on clinical trials. We utilized ASCO irAE and CTCAE v5 guidelines for toxicity grading. Logistic regression assessed the effect of clinical variables on irAEs, adjusting for covariates. Results: We identified 233 pts with a median age of 51 ± 12 years; 62% with stage II and 35% with stage III TNBC; 25% were Hispanic/Latino, 21% non-Hispanic Black and 42% were non-Hispanic White. In total, 80 pts (34%) developed 100 separate irAEs (94 with definite and 6 with possible/probable attribution). The most common irAEs were endocrine (52%) followed by gastrointestinal (23%). Grade ≥ 3 irAE occurred in 26 instances, with the most common being gastrointestinal (13 instances). A fatal irAE occurred in 2 pts where both were colitis. A total of 26 irAEs resulted in hospitalization, 45 required systemic steroids, and 15 required additional immunosuppressive therapy. Most (66) irAEs were unresolved at last follow up, although the majority had improved to grade 1 (37/66) and 32 patients discontinued pembrolizumab early due to irAEs. No clinical factor (race, stage, tumor grade, age, body mass index) was associated with development of an irAE. Conclusions: In this real-world diverse population, we identified a similar rate and severity of irAEs as reported in the KEYNOTE-522 trial. Hospitalizations occurred in 26% of irAEs while most developed persistent immune toxicity. Gastrointestinal irAEs were more common compared to KEYNOTE-522 reported data. Research is needed to better predict and mitigate the burden of irAEs and to improve the long-term survivorship care of pts with early TNBC pts who receive pembrolizumab. [Table: see text]