Trastuzumab In Neoadjuvant Treatment Research Articles

The relationship between PIK3CA mutations and survival in patients with human epidermal growth factor receptor 2–positive breast cancer receiving pyrotinib combined with trastuzumab for neoadjuvant treatment.

e12637 Background: Our previous study suggested that HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to achieve a pathological complete response (pCR) from pyrotinib combined with trastuzumab in the neoadjuvant setting. The relationship of PIK3CA mutations and survival remains unknown. Methods: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between PIK3CA mutations and event-free survival (EFS) and overall survival (OS) were explored. Results: Among the cohort of 50 cases, five patients dropped out during treatment due to various reasons, whereas the other 45 patients were followed up until August 31, 2023. The median follow-up was 36.1 months, and mEFS and mOS were not reached yet. Kaplan-Meier estimated 3-year EFS rate and OS rate were 91.1% (95% confidence interval [CI]=83.2%-99.8%) and 97.1% (95% CI=91.8%-100%), respectively. Patients with wild-type PIK3CA tended to achieve a better 3-year EFS rate (96.2% vs 63.2%, hazard ratio [HR]=0.18, 95% CI=0.02-1.59, log-rank P = 0.081) compared with the patients with mutated PIK3CA. Besides, patients with pCR showed a better 3-year EFS rate (96.2% vs 84.2%, HR=0.16,95% CI=0.02-1.45, log-rank P = 0.063) compared with the patients without pCR. Conclusions: HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab in the neoadjuvant setting, but this conclusion still needs to be confirmed by large-sample studies and long-term follow-up results. Clinical trial information: 1900022293.

181P Pegylated liposomal doxorubicin (PLD) combined with docetaxel and trastuzumab in neoadjuvant treatment for HER2-positive breast cancer: A multicenter, randomized, phase II, open-label trial

Trastuzumab based chemotherapy is the standard regimen for HER2+ breast cancer (BC) in neoadjuvant trerapy. Combination of trastuzumab and anthracycline is generally avoided clinically due to the cardiotoxicity of the two drugs. PLD is less cardiotoxic compared with traditional anthracyclines. Here, we conducted this prospective study to evaluate the efficacy and safety of PLD (A) + docetaxel (T) + trastuzumab (H) in neoadjuvant treatment for HER2+ BC.

Neoadjuvant chemotherapy with biosimilar trastuzumab in human epidermal growth factor receptor 2 overexpressed non-metastatic breast cancer: patterns of use and clinical outcomes in India.

BackgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator.MethodsWe conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator (n = 34 (33%)) and biosimilar (n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records.ResultsA total of 135 patients were analysed with a median age of 51 years (range: 23–82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3–114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients.ConclusionAccess to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.

Effect of Additional Trastuzumab in Neoadjuvant and Adjuvant Treatment for Patients with Resectable HER2-Positive Gastric Cancer.

Recent studies have reported a beneficial role of trastuzumab in neoadjuvant treatment (NAT) among resectable gastric cancer (GC) patients; however, the effect of adjuvant treatment (AT) combined with trastuzumab is understudied. We performed a retrospective cohort study to compare chemotherapies with or without trastuzumab among human epidermal growth factor receptor 2-positive (HER2 +) locally advanced GC patients in the AT and NAT settings, respectively. We enrolled 208 HER2 + resected GC patients who underwent perioperative/postoperative treatment in 2010-2019 in a single-centered hospital, including 135 AT patients and 73 NAT patients. We used inverse probability of treatment weighting (IPTW) to balance potential confounding factors between the treatment groups, and estimated the treatment effect of trastuzumab. Pathological and survival outcomes were evaluated. The number of trastuzumab-exposed patients in the AT and NAT cohorts was 31 (23.0%) and 34 (46.6%), respectively. After IPTW adjustment, AT combined with trastuzumab showed a better overall survival (OS) over chemotherapy alone (p = 0.023). In IPTW-adjusted NAT analysis, trastuzumab-exposed patients had an improvement in tumor pathological regression and downstaging, with lower tumor regression grade scores (p = 0.002), ypTNM stages (p < 0.001), ypN stages (p = 0.035), and ypT stages (p < 0.001). Loss of HER2 positivity following trastuzumab treatment was observed in NAT patients; however, we did not observe any significant effect of trastuzumab on OS (p = 0.126). Given the improvement in tumor regression and downstaging among NAT patients, and the OS benefit in AT patients, trastuzumab could be considered a promising treatment for locally advanced HER2 + GC patients. In particular, re-evaluation of HER2 status should be considered following NAT combined with trastuzumab.

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study.

BACKGROUNDTriplet chemotherapy, with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer (GC). An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results.AIMTo determine safety and efficacy of TeFOX perioperative regimen.METHODSThis monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC. TeFOX consist in docetaxel (50 mg/m²) with oxaliplatin 85 mg/m² and and leucovorin (400 mg/m2) 5 FU bolus (400 mg/m2) on day 1, followed by continuous infusion of 5FU for 46 h (2400 mg/m2) every 2 wk.RESULTSThirty-three consecutive patients were included in this retrospective study. Eighteen patients have a gastroesophageal junction cancer and 11 have a GC. Median follow-up of surviving patients was 32 mo. R0 resection was obtained in 30 (91) patients. Twelve patients (36) had a pathological complete response and 8 (24) patients a nearly complete pathological response. Median OS and PFS were not reached at data base lock. We have observed 6 metastatic relapses and 1 localized relapse. No relapse was observed in patients with pathological complete responses. The most common grade 3-4 adverse events were peripheral neuropathy (21) and asthenia (20).CONCLUSIONTeFOX regimen could be safely administrated in perioperative treatment of localized GC. TeFOX and the FLOT regimen have comparable efficacy and safety profiles.

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial

CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer. In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m2], epirubicin [75 mg/m2], and cyclophosphamide [500 mg/m2]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting. Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%). CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer. Celltrion Inc.

Application of molecular targeted agents in comprehensive treatment of gastrointestinal cancer

Targeted agents increase response rates and improved overall survival in treatment of metastatic gastrointestinal cancer. Therefore, physicians pay more attention to the role of targeted agents in treatment of local advanced gastrointestinal cancer. The clinical trials are ongoing to evaluate the efficacy of Trastuzumab in neoadjuvant treatment of local advanced gastric cancer with HER-2 gene over expression. Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status. A phase III( clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation. Current evidence showed that neoadjuvant therapy of targeted agents did not prolong survival of patients with resectable liver metastasis. However, this is controversial. In neoadjuvant therapy of local advanced rectal cancer, Cetuximab did not improve the rates of pathological complete response in most of the phase II( trials. Furthermore, there are no phase III( trials to assess the role of Bevacizumab. Compared to chemotherapy alone for metastatic cancer, it is more important to evaluate the interaction and synergistic action of targeted agents, cytotoxic drugs, surgery and radiation, to make a scientific multidisciplinary model in comprehensive treatment of local advanced cancer.