Total Pathologic Complete Response Research Articles

Neoadjuvant inetetamab and pertuzumab with taxanes and carboplatin (TCbIP) In locally advanced HER2-positive breast cancer: a prospective cohort study with propensity-matched analysis

BackgroundInetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated.MethodsThis prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints.ResultsForty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs.ConclusionNeoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment.Trial registrationNCT05749016 (registration date: Nov 01, 2021).

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.

QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial

BackgroundThis randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative.MethodsEligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32.ResultsAmong the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups.ConclusionsQL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer.Trial registrationChinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

Neoadjuvant pyrotinib and inetetamab in combination with chemotherapy for locally advanced HER2-positive breast cancer (NeoPICD study): A prospective, multicenter, open-label, single-arm study.

e12627 Background: Inetetamab, a novel monoclonal antibody targeting HER2, alters the Fc region amino acids, which induces ADCC stronger than trastuzumab. Pyrotinib is a small chemical inhibitor of pan-HER receptor tyrosine kinase. The globally recommended first-line neoadjuvant treatment for HER2-positive breast cancer is chemotherapy and two large-molecule monoclonal antibodies, which have unsatisfactory benefits for 50% of patients. This study aims to investigate the effectiveness and safety of targeted medicines, specifically inetetamab and pyrotinib, in conjunction with chemotherapy for patients diagnosed with locally advanced HER2-positive breast cancer. Methods: The trial was structured as a multicenter, open-label, single-arm, prospective study. 143 treatment-naive HER2-positive locally advanced breast cancer patients were planned for the trial. Eligible patients will be administered six cycles of neoadjuvant treatment, including carboplatin (AUC=6mg/mL×min, ivgtt), doxorubicin (75mg/m2, ivgtt), inetetamab (initial loading dosage of 8mg/kg, maintenance dose of 6mg/kg), and pyrotinib (400mg/day, po). The surgery was conducted after the neoadjuvant phase, subsequent to a one-year course of targeted therapy with inetetamab and pyrotinib. The primary endpoint of the study is the total pathologic complete response (tpCR). The secondary endpoints include event-free survival (EFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), neurologic disease-free survival (NDFS), overall survival (OS), and safety. Results: A cohort of 70 patients was enrolled between Nov. 27, 2021 and Feb. 1, 2024. Most patients completed the six-cycle neoadjuvant therapy with inetetamab, pyrotinib, and chemotherapy. The pathological findings of 49 patients who had radical surgery revealed that 65.3% (32/49, 95% CI, 0.515-0.791) of them achieved tpCR (ypT0/Tis ypN0). The initial subgroup analysis revealed that among patients with negative hormone receptors, the rate of tpCR was 80.0% (24/30, 95% CI, 64.8-95.2). Moreover, hormone receptor was statistically determined to be an independent factor influencing the effectiveness of the new treatment regimen ( p=0.032). The prevailing grade 3 or more severe adverse events included anemia (12.8%), diarrhea (10.0%), leukopenia (4.2%), liver dysfunction (4.2%) and renal dysfunction (4.2%). As of now, no treatment-related deaths have been documented. Conclusions: The ongoing study is actively enrolling participants. Preliminary findings from the study indicate that the combination of neoadjuvant inetetamab and pyrotinib with chemotherapy has demonstrated satisfactory effectiveness and manageable side effects. This offers a promising alternative for patients with locally advanced breast cancer that is HER2-positive. Clinical trial information: NCT06234137 .

Efficacy, safety, and predictive biomarkers of dalpiciclib combined with letrozole, pertuzumab and trastuzumab as neoadjuvant therapy in HR+/HER2+ breast cancer: A phase II study.

e12621 Background: HR+/HER2+ breast cancer is a unique subtype of breast cancer. Between ER and HER2 crosstalk pathways may affect the sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ breast cancer. Current therapies for HER2-positive breast cancer have demonstrated limited efficacy in patients with HR+/HER2+ breast cancer. This Phase II trial aimed to assess the efficacy and safety of a neoadjuvant regimen combining trastuzumab, pertuzumab, dalpiciclib (a cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with HR+/HER2+ breast cancer, alongside the exploration of efficacy biomarkers. Methods: Patients were administered six 28-day cycles of dalpiciclib (150 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), pertuzumab (840mg loading dose followed by 420mg maintenance dose on day 1), prior to surgery. The primary endpoint was total pathological complete response (tpCR, ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, change in Ki-67 level from baseline to one cycle of treatment and to surgery, and safety. For biomarkers analysis, next-generation sequencing was performed on pre-treatment tissue and circulating tumor DNA (ctDNA) at various time points before surgery. Results: A total of 14 patients who completed the neoadjuvant treatment and surgery between July 12, 2022 and August 12, 2023 were enrolled. A 50.0% (7 out of 14) tpCR and bpCR rate was observed, with an ORR of 92.9%. Significant reductions in Ki-67 levels were noted after both one ( P<0.05) and six cycles of neoadjuvant therapy ( P<0.05). Grade 4 neutropenia was reported in one case, with no fatalities. The most common grade 3 adverse events were neutropenia (10 [71.4%]) and leukopenia (8 [57.1%]). NGS identified frequent mutations in TP53 (84.6%), PIK3CA (53.8%), and ARID1A (30.8%). Cell cycle pathway gene alterations correlated with a higher pCR rate (80% vs 25%, P=0.103). Eight (61.5%) patients had positive ctDNA at baseline, and ctDNA positivity decreased significantly post-neoadjuvant treatment ( P<0.05). Patients with positive ctDNA at baseline without clearance post-treatment exhibited a trend towards a lower pCR rate. Conclusions: This combination neoadjuvant regimen of dalpiciclib, letrozole, pertuzumab and trastuzumab demonstrated promising pathological responses and manageable safety in patients with HR+/HER2+ breast cancer. The predictive value of genetic alterations and ctDNA status for treatment efficacy warrants further investigation. Clinical trial information: ChiCTR2200062114.

A propensity-matched analysis of the efficacy and safety of neoadjuvant inetetamab and pertuzumab with paclitaxel and carboplatin (TCbIP) on locally advanced HER2-positive breast cancer.

e12609 Background: Inetetamab is an Fc segment-modified innovative anti-HER2 monoclonal antibody. It has been proven to be effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in the neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remains to be validated. This study aimed to evaluate the efficacy and safety of Inetetamab-based neoadjuvant therapy (TCbIP). Methods: In this prospective cohort study, we investigated the efficacy and safety of TCbIP in neoadjuvant therapy for HER2-positive LABC, and compared with TCbHP regimen (trastuzumab combined with pertuzumab, paclitaxel, and carboplatin) with propensity score matching (PSM). Thirty-four patients (clinical stage IIA-IIIC, HER2-positive LABC) were prospectively enrolled in this study and treated with the TCbIP regimen. The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. Results: The pCR rate of 28 patients who finished surgery was 60.7%, and was comparable and slightly higher (60.7% vs. 53.6%, P = 0.510) than the TCbHP group in PSM. The ORR was 96.4% and DCR reached 100.0%. The most common ≥grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. Conclusions: Neoadjuvant therapy with TCbIP resulted in good efficacy and safety in patients with HER2-positive LABC, and might be another promising option for neoadjuvant treatment. Clinical trial information: NCT05749016 .

Optimal neoadjuvant treatment and prognostic factors in patients with HR-positive/HER2-positive early or locally advanced breast cancer: A national real-world study in China.

e12514 Background: Few data have been reported regarding breast cancer (BC) population characterized by HR+/HER2+ especially in a real-world setting in China. This analysis aimed at identifying differences in short-term treatment outcomes of different neoadjuvant therapy (NAT) regimens, effects of the demographics and clinical features on short-term outcomes of NAT, and further understanding the prognostic factors related to those outcomes in HR+/HER2+ early (EBC) or locally advanced BC (LABC) pts by using dataset from National Cancer Information Database (NCID) in China. Methods: This retrospective, multicenter, real-world study used electronic medical record data from NCID. We analyzed HR+/HER2+ EBC or LABC Chinese pts who were initially diagnosed between Jan 1, 2019 and May 31, 2022 and received NAT followed by surgery during study period. Primary endpoints included total pathological complete response (tpCR) and breast pCR (bpCR). Secondary endpoints included disease-free survival (DFS) and event-free survival (EFS). Results: 3792 pts from NCID covering 51 hospitals, 26 provinces met inclusion criteria and were included. After controlling for age and post-surgery N staging, 1-, 2- and 3-yr DFS was similar between trastuzumab (T) and T+pertuzumab (P) NAT subgroup (92.79%, 87.20% and 83.32% vs 94.83%, 88.82% and 87.88%; p=0.1120). 1-, 2- and 3-yr EFS was higher in T+P subgroup (T vs T+P: 85.24%, 82.35%, 77.01% vs 90.86%, 89.65%, 82.78%; p = 0.0003). Logistic regression multivariate analysis showed improved tpCR and bpCR was independently positively associated with receiving T+P NAT (vs T: both p < 0.0001), platinum NAT (vs anthracycline: p = 0.0071 and 0.0122, resp.), while negatively associated with receiving no targeted therapy (vs T: p = 0.0002 and < 0.0001, resp.), ≥ 65 yrs (vs > 40 yrs, < 64 yrs: p = 0.0116 and 0.0290, resp.), or post-surgery ER positive (vs negative: both p < 0.0001). Conclusions: HR+/HER2+ EBC or LABC gained short- and long-term benefit from HER2 dual-blockade therapy in clinical practice. Prognostic factors for improved tpCR and bpCR included T+P and platinum NAT, whereas ≥ 65 yrs and post-surgery ER+ were predictive of decreased tpCR and bpCR. [Table: see text]

Neoadjuvant pegylated liposomal doxorubicin-containing chemotherapy in combination with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer: A randomized phase II study (METIS).

596 Background: In the neoadjuvant phase, anti-HER2 therapy is usually delayed when combined with anthracycline-containing chemotherapy regimens, since conventional anthracycline and anti-HER2 agents cannot be given simultaneously. Pegylated liposomal doxorubicin (PLD) is a modified form of doxorubicin that can lower the risk of heart damage while preserving its anticancer activity. In this study, we aimed to explore whether PLD could replace conventional anthracycline and be used earlier with anti-HER2 agents to enhance neoadjuvant efficacy without increasing cardiotoxicity. Methods: The METIS study was an investigator-initiated, multicenter, open-label, randomized, phase II study conducted at 11 centers in China. Patients aged 18 to 70 years old with previously untreated stage II–III histologically documented HER2-positive breast cancer were randomly assigned (1:1) to receive PLD-containing or epirubicin-containing neoadjuvant chemotherapy. The PLD-containing regimen consisted of 4 cycles of PLD (35 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of a taxane of the investigator's choice (docetaxel, paclitaxel, or nab-paclitaxel). The epirubicin-containing regimen consisted of 4 cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of a taxane of the investigator's choice. Both regimens included trastuzumab (8 mg/kg loading dose, then 6 mg/kg maintenance dose) and pertuzumab (840 mg loading dose, then 420 mg maintenance dose) every 3 weeks. Trastuzumab and pertuzumab were given with all chemotherapy cycles in the PLD-containing group, and with the taxane cycles only in the epirubicin-containing group. The primary end point was investigator-assessed total pathological complete response (tpCR) rate in the intention-to-treat population. Results: From August 2019 to March 2023, 156 were enrolled and randomly assigned to receive PLD-containing (n=80) or epirubicin-containing (n=76) treatment. At date of data analysis, the median follow-up duration was 16.3 months. The PLD-containing treatment group had a higher rate of pathological complete response (67.5%, 95% CI 56.1-77.6) than the epirubicin-containing group (48.7%, 95% CI 37.0-60.4), with a rate difference of 18.8% (p=0.033). Only one patient in the epirubicin-containing group experienced a grade 3 decrease in left ventricular ejection fraction, while none did in the PLD-containing group. Other adverse events were similar in both groups. Conclusions: A combination of PLD and cyclophosphamide with trastuzumab and pertuzumab, followed by a taxane, trastuzumab, and pertuzumab, significantly increased the rate of tpCR without more cardiotoxicity in neoadjuvant treatment for early-stage HER2-positive breast cancer patients. Clinical trial information: NCT04172259 .

Peony exploratory analyses of biomarker changes: From baseline to surgical samples in patients with HER2+ breast cancer.

e15136 Background: PEONY (NCT02586025) is a randomized, multicenter, double-blind, placebo-controlled, phase III trial evaluating neoadjuvant and adjuvant pertuzumab/placebo with trastuzumab and docetaxel in HER2-positive early/locally advanced breast cancer. We previously reported that pertuzumab showed an improved efficacy vs. placebo in terms of total pathological complete response (tpCR), event-free survival and disease-free survival (DFS), as well as in pre-defined biomarker subgroups. Limited data are available on biomarker changes after neoadjuvant treatment in the Asian population. Thus, we aim to (1) describe the biomarker changes from baseline to surgical samples after HER2 targeted neoadjuvant therapy, and (2) explore the association of surgical biomarkers and DFS. Methods: This study will focus on biomarkers of tumor tissue samples collected at baseline and surgery among 218 non-tpCR patients, due to limited samples collected at disease progression. Samples were tested using Immunohistochemistry (IHC) for HER3, PTEN, CD8 and PD-L1. Both HER2/HER3 mRNA expression and PIK3CA mutation were assessed using a PCR based methodology. The statistical analyses were using R (4.1.3). Biomarkers were categorized as high/low either by median derived from baseline samples, or with well-established cutoffs, e.g. HER2 IHC of 3+ vs. 1/2+ and PD-L1 at 1%. The changes of biomarkers were examined among the paired samples using Fisher’s exact test and depicted by alluvial plots. Cox proportional hazard regression analysis was performed to examine the association between surgical biomarkers and DFS in pooled arms. Results: Since the surgical biomarkers are only evaluable among patients with residual disease, patients in this analysis had a higher stage, and were more likely to be node+. Of 166 paired samples, more patients show a decrease in HER2 and HER3 mRNA/IHC, PTEN IHC from baseline to surgery. PIK3CA mutation status remained the same among the majority of patients (n = 154, 95%). Immune-related biomarkers, PD-L1 and CD8, are more enriched in surgical samples compared to baseline. All these observations are similar between the two arms. No clear association has been shown in most of the biomarkers, except for PIK3CA, with DFS. Surgical tumor samples with PIK3CA mutation detected trended with a worse DFS than those with no PIK3CA mutation detected [HR: 1.81 (95% CI: 0.94 – 3.49)]. Conclusions: Of baseline and surgery paired samples, most biomarkers showed a change, except for PIK3CA mutation status. In pooled analyses, we only observed a trend of PIK3CA mutation detected in surgical samples with a worse DFS, which is in line with the association observed with baseline PIK3CA mutation status. No other associations were found between surgical biomarkers and DFS. These findings may suggest that despite biomarker changes patients continue to benefit From HER2 therapies and dual blockade. Clinical trial information: NCT02586025 .

Abstract PO1-03-11: Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled Study

Abstract Background: Triple-negative breast cancer (TNBC) is recognized for its aggressive nature and unfavorable prognosis. Immune checkpoint inhibitors have demonstrated promising antitumor activity in both neoadjuvant and metastatic settings. This study aimed to assess the efficacy and safety of camrelizumab, an anti-PD-1 antibody, in conjunction with chemotherapy as a neoadjuvant treatment for early-stage TNBC. Methods: This two-phase prospective, multicenter, randomized controlled study was initiated with the enrollment of previously untreated stage II-III TNBC patients in the first phase. They received neoadjuvant therapy comprising six 3-week cycles of camrelizumab (200 mg, q3w), along with nab-paclitaxel (220 mg/m2, q3w) and carboplatin (AUC 5, q3w). In the second phase, patients were enrolled and randomized 1:1 to either the camrelizumab plus nab-paclitaxel and carboplatin group or the nab-paclitaxel plus carboplatin group. The present report covers the data from the first phase of the study. The primary endpoint was the total pathological complete response (tpCR, ypT0/is ypN0) rate. Secondary endpoints included breast pathological complete response (bpCR, ypT0/is) rate, objective response rate (ORR), event-free survival (EFS), residual cancer burden (RCB), and safety. This study is registered with ClinicalTrials.gov, under the identifier NCT04907344. Results: Between September 2021 and March 2023, 39 patients were enrolled in the first phase. A total of 35 (89.7%) were node-positive. Among the 32 patients with evaluable efficacy, the tpCR rate was 59.4% (19/32), and the bpCR rate was 68.8% (22/32). The ORR at the end of neoadjuvant treatment stood at 87.2% (34/39). Among the 39 patients, 11 (28.2%) experienced grade 3 or higher treatment-related adverse events, the most common of which were thrombocytopenia (6 [15.4%]), leucopenia (5 [12.8%]), neutropenia (5 [12.8%]), alanine aminotransferase increased (2 [5.1%]), aspartate aminotransferase increased (1 [2.6%]), and hypothyroidism (1 [2.6%]). Adverse events leading to discontinuation of any agent occurred in 5 (12.8%) patients, while adverse events leading to delay in treatment occurred in 7 (17.9%) patients. Serious treatment-related adverse events were reported by 4 (10.4%) patients. Conclusions: In patients with early TNBC, the neoadjuvant treatment of camrelizumab in combination with nab-paclitaxel and carboplatin demonstrated a high pCR rate with an acceptable safety profile. The second phase of the study is currently in progress to validate these findings. Citation Format: Weipeng Zhao, Xin Wang, Bin Zhang, Yehui Shi, Chen Wang, Xu Wang, Shufen Li, Chunfang Hao, Ning Lu, Yongsheng Jia, Li Zhang, Lan Zhang, Weixin Sun, Xuchen Cao, Zhongsheng Tong. Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled Study [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 PO1-03-11.

Abstract PO2-02-05: CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory trial

Abstract Background: Patients with HR-positive, HER2-negative breast cancer respond poorly to neoadjuvant chemotherapy. The phase 3 DAWNA-1 and DAWNA-2 studies have proved that adding dalpiciclib (a CDK4/6 inhibitor) to endocrine therapy can significantly improve progression-free survival in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. However, the evidence of dalpiciclib in the neoadjuvant setting is limited. This study aimed to explore the efficacy and safety of dalpiciclib plus letrozole as neoadjuvant therapy in in patients with HR-positive, HER2-negative stage II-III breast cancer. Methods: In this multicenter, single-arm exploratory trial (NCT05512780), adult postmenopausal women with HR-positive (estrogen receptor >10%), HER2-negative stage II-III invasive breast cancer were enrolled. Patients received oral dalpiciclib (150 mg on days 1-21 of each 28-day cycle) and oral letrozole (2.5 mg once daily) for 4 cycles, followed by surgery. The primary endpoint was objective response rate (ORR), assessed by investigator according to the Response Evaluation Criteria In Solid Tumors version 1.1. Secondary endpoints included complete cell cycle arrest (CCCA, defined as Ki-67 < 2.7% on day 15 of the first cycle) rate, total pathological complete response (tpCR; ypT0/is ypN0) rate, residual cancer burden (RCB) 0-I rate, and safety. Results: Between June 2022 and January 2023, 41 patients were screened at 9 sites, and 35 patients were enrolled and received at least one dose of study drug. The median age was 66 years (range, 52-83), and the median baseline Ki-67 level was 20% (range, 4%-40%). The majority of patients had T2 disease (65.7%), lymph node-positive disease (88.6%), and stage II disease (IIA: 45.7%; IIB: 40.0%). The ORR was 35.5% (11/31) at 8 weeks and 51.7% (15/29) at 16 weeks in patients with evaluable response. The CCCA rate was 70.0% (21/30) in patients with available data. Four patients refused surgery and chose to continue the drug therapy. Of 27 patients who had undergone surgery, one (3.7%) patient had tpCR and RCB 0. Of 35 patients, the most common adverse events were neutrophil count decreased (74.3%), white blood cell decreased (68.6%), anemia (34.3%), and fatigue (31.4%). The most common grade 3 or higher adverse event was neutrophil count decreased (45.7%). No febrile neutropenia or treatment-related deaths occurred. Conclusions: This is the first prospective study of neoadjuvant dalpiciclib in patients with HR-positive, HER2-negative breast cancer. The findings suggest the promising tumor response to neoadjuvant dalpiciclib plus letrozole in postmenopausal patients with HR-positive, HER2-negative breast cancer, with a manageable safety profile. This combination can effectively suppress the tumor cell proliferation, as reflected by change in Ki-67 level. Citation Format: Lina Zhang, Chao Yang, Jie Ma, Yuntao Li, Ruizhen Luo, Jianjun Han, Xiaochun Wang, Zhisheng Zhang, Li Ma, Haifeng Cai, Xiangshun Kong, Zunyi Wang, Xinping Zhou, Yueping Liu, JiaJie Shi, Yanshou Zhang, Meiqi Wang, Jiaxing Wang, Cuizhi Geng. CDK4/6 inhibitor dalpiciclib combined with letrozole as neoadjuvant therapy in postmenopausal patients with hormone receptor-positive, HER2-negative stage II-III breast cancer: a single-arm exploratory 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 PO2-02-05.

Abstract PO1-27-01: Comparing the Efficacy and Safety of TQB2440 versus the Reference Pertuzumab for the Treatment of HER2-Positive Early or Locally Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase 3 Trial

Abstract Background: Pertuzumab is a recombinant humanized monoclonal antibody targeting the extracellular dimerization domain II of HER2. On September 30, 2013, the FDA have granted accelerated approval of a pertuzumab regimen for neoadjuvant treatment of patients (pts) with high-risk, HER2-positive early stage breast cancer. TQB2440 is a pertuzumab (Perjeta®, Roche) biosimilar. This study aimed to compare the efficacy and safety of TQB2440 and the reference pertuzumab combined with trastuzumab and docetaxel in pts with HER2-positive early or locally advanced breast cancer. Methods: In this multicenter, randomized, double-blind phase 3 study, eligible pts were aged 18-75 with operable HER2-positive (IHC 3+ or ISH+) clinical stage II-IIIC breast cancer negative for ER/PR and had an ECOG PS of 0-1. The pts were randomly assigned to receive either TQB2440 or the reference pertuzumab (Perjeta®) (840 mg on day 1, cycle 1, followed by 420 mg on cycle 2-4, q3w) added to trastuzumab (8 mg/kg on day 1, cycle 1, followed by 6 mg/kg for cycles 2-4, q3w) + docetaxel (75 mg/m2, cycle 1-4, q3w). The pts then underwent surgery followed by adjuvant treatment with FEC regimens (fluorouracil 600 mg/m², epirubicin 90 mg/m², cyclophosphamide 600 mg/m², cycle 5-7, q3w), then TQB2440 (840 mg on day 1, cycle 8, followed by 420 mg on cycle 9-20, q3w) + trastuzumab (8 mg/kg on day 1, cycle 8, followed by 6 mg/kg for cycles 9-20, q3w) or until disease progression or intolerable toxicity. The primary endpoint was total pathologic complete response (tpCR) by independent review committee (IRC). Equivalence was established if the 90% confdence intervals (CIs) of the relative ratio [RR] within the interval of 0.76 to 1.32. Secondary endpoints included breast pathologic complete response (bpCR) by IRC, tpCR & bpCR by investigator, breast conserving surgery (BCS) rates, objective response rate (ORR), event-free survival (EFS), disease-free survival (DFS), OS and safety. Results: Between October 21, 2020, and November 21, 2022, 412 pts were enrolled (TQB2440 group, n=207; the reference pertuzumab group, n=205). Data cutoff was November 30, 2022. In the intention-to-treat (ITT) population, the tpCR by IRC of the TQB2440 group and the reference drug group were 58.94% and 58.05%, respectively. The RR was 1.02 (90% CI, 0.89, 1.16), which was within the predefined equivalence interval of 0.76 to 1.32. There was no statistically significant difference in the bpCR by IRC between the TQB2440 group and the reference pertuzumab group (67.63% [95% CI, 60.80%, 73.95%] vs. 63.90% [95% CI, 56.92%, 70.48%], P=0.4249). The BCS rate also comparable between the two groups with 13.04% (95% CI, 8.77%, 18.41%) vs. 13.17% (95% CI, 8.86%, 18.58%) (P=0.9695). Additionally, the results of the PP (per-protocol) population were similar to those of the ITT population. The incidence of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were similar between the TQB2440 group and the reference pertuzumab group with 79.71% vs. 75.98% and 49.28% vs. 41.67%, respectively. Conclusion: In patients with HER2-positive early or locally advanced breast cancer, TQB2440 demonstrated equivalent efficacy and similar safety to the reference pertuzumab. Clinical trial information: NCT05985187. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd Citation Format: Qingyuan Zhang, Shusen Wang, Nanlin Li, Qiao Cheng, Yu ren, Xuchen Cao, Jianjun Huang, Caigang Liu, Hongwei Yang, Limin Wei, Zhangjun Song, Huadong Zhao, Fangling Ning, Xiaojia Wang, Dehong Zou, Xiaohua Zeng, Jie Hao, Yunjiang Liu, Huijuan Wang, Nie Jianyun, Liang Li, Lina Liu, Tao Sun, Xiaobo Hu, Zhenhua Zhai, Huihua Xiong, Yuanqi Zhang, Enxiang Zhou, Jing Sun, Zhenhai Cai, Antai Zhang, Shui Wang, Junyang Mo, Qun Su, Xiuheng Qi, Guoren Zhou, Shuqun Zhang, Guozhong Cui, Wei Wang, Mingjiang Fan, Xinyu Qian, Xinhong Wu, Zhihong Wang, Jiuda Zhao, Yonghui Luo, Yanming Zhang, Fuguo Tian, Jiye Zhang, Dongning Chai, Qingshan Li. Comparing the Efficacy and Safety of TQB2440 versus the Reference Pertuzumab for the Treatment of HER2-Positive Early or Locally Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase 3 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 PO1-27-01.

Abstract PO1-01-02: Final analysis of neoadjuvant chemotherapy with pegylated liposomal doxorubicin/cyclophosphamide followed by taxanes with full-course trastuzumab/pertuzumab for HER2-positive breast cancer: a single-arm, phase II study

Abstract Background: The optimal neoadjuvant treatment regimen for HER2-positive breast cancer remains unclear, especially regarding the use of anthracycline. We conducted a prospective phase II study to evaluate sequential neoadjuvant chemotherapy with pegylated liposomal doxorubicin (PLD)/cyclophosphamide followed by taxanes in the presence of full-course trastuzumab/pertuzumab in HER2-positive early breast cancer patients. Methods: In this single-arm, open-label, multicenter, phase II study, eligible patients with confirmed HER2-positive early breast cancer were recruited from four independent hospitals. Patients received four cycles of PLD (35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (ypT0/is ypN0, tpCR). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, the proportion of patients requiring breast-conserving surgery, and safety. For biomarkers analysis, tumor tissues were collected at baseline and evaluated for Topoisomerase 2 Alpha (TOP2A) expression assessed prospectively with immunohistochemistry (IHC) assay by independent pathologists. Results: Between May 27, 2020 and May 11, 2022, 78 eligible patients were treated and underwent surgery, of whom 42 (53.8%) patients underwent breast-conserving surgery. After neoadjuvant therapy, 47 (60.3%, 95% CI, 48.5%-71.2%) patients achieved a tpCR in the breast and axilla. The bpCR was observed in 49 (62.8%) patients. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. All (100%) patients achieved disease control since the end of the first cycle. No correlations between clinicopathological variables and pathological response were observed. Grade 3 or worse AEs occurred in 35 (44.9%) patients. Nine (11.5%) patients experienced asymptomatic LVEF reduction (≥10% from baseline), but all with a minimum value of >55%. No treatment-related surgical delay or death occurred. For biomarkers analysis, the status of TOP2A was not found to be associated with pCR or 4th-cycle ORR. Conclusions: This dual HER2-blockade plus polychemotherapy as sequential neoadjuvant regimen demonstrates promising anti-tumor activity and acceptable tolerability for patients with HER2-positive breast cancer. Citation Format: Yaping Yang, Liang Jin, Yudong li, Fengxia Gan, Nanyan Rao, Jun Zhang, Ruifa Feng, Zhenzhen Liu, Qiang Liu. Final analysis of neoadjuvant chemotherapy with pegylated liposomal doxorubicin/cyclophosphamide followed by taxanes with full-course trastuzumab/pertuzumab for HER2-positive breast cancer: a single-arm, phase II study [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 PO1-01-02.

Neoadjuvant–adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months’ median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32–0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30–0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer.

Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.

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.

A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer.

Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II-III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%-84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0-I was 75% (95% CI, 46.8%-91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5%-70.5%) at baseline to 17.2% (95% CI, 0.7%-33.7%) after neoadjuvant therapy (p=0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment-related deaths occurred. This four-drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study.

Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC). In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity). Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin. This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Development and Validation of an Interpretable Machine Learning Prediction Model for Total Pathological Complete Response after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: Multicenter Retrospective Analysis.

Objective: This study aims to develop an interpretable machine learning (ML) model to accurately predict the probability of achieving total pathological complete response (tpCR) in patients with locally advanced breast cancer (LABC) following neoadjuvant chemotherapy (NAC). Methods: This multi-center retrospective study included pre-NAC clinical pathology data from 698 LABC patients. Post-operative pathological outcomes divided patients into tpCR and non-tpCR groups. Data from 586 patients at Shanghai Ruijin Hospital were randomly assigned to a training set (80%) and a test set (20%). In comparison, data from our hospital's remaining 112 patients were used for external validation. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Predictive models were constructed using six ML algorithms: decision trees, K-nearest neighbors (KNN), support vector machine, light gradient boosting machine, and extreme gradient boosting. Model efficacy was assessed through various metrics, including receiver operating characteristic (ROC) curves, precision-recall (PR) curves, confusion matrices, calibration plots, and decision curve analysis (DCA). The best-performing model was selected by comparing the performance of different algorithms. Moreover, variable relevance was ranked using the SHapley Additive exPlanations (SHAP) technique to improve the interpretability of the model and solve the "black box" problem. Results: A total of 191 patients (32.59%) achieved tpCR following NAC. Through LASSO regression analysis, five variables were identified as predictive factors for model construction, including tumor size, Ki-67, molecular subtype, targeted therapy, and chemotherapy regimen. The KNN model outperformed the other five classifier algorithms, achieving area under the curve (AUC) values of 0.847 (95% CI: 0.809-0.883) in the training set, 0.763 (95% CI: 0.670-0.856) in the test set, and 0.665 (95% CI: 0.555-0.776) in the external validation set. DCA demonstrated that the KNN model yielded the highest net advantage through a wide range of threshold probabilities in both the training and test sets. Furthermore, the analysis of the KNN model utilizing SHAP technology demonstrated that targeted therapy is the most crucial factor in predicting tpCR. Conclusion: An ML prediction model using clinical and pathological data collected before NAC was developed and verified. This model accurately predicted the probability of achieving a tpCR in patients with LABC after receiving NAC. SHAP technology enhanced the interpretability of the model and assisted in clinical decision-making and therapy optimization.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study

BackgroundThis prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy.MethodsA total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. Control group: 83 patients received EC-TH regimen. The chi-square test, Fisher’s exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs).ResultsIn the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred.ConclusionThe efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.