Misconception on the duration of ado-trastuzumab emtansine treatment for HER2-positive early breast cancer

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High score of LDH plus dNLR predicts poor survival in patients with HER2-positive advanced breast cancer treated with trastuzumab emtansine

Objective To investigate the prognostic value of derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) in patients with advanced HER2 positive breast cancer treated with trastuzumab emtansine. Methods Fifty one patients with advanced HER2 positive breast cancer who received T-DM1 treatment in Harbin Medical University Cancer Hospital were selected. The clinical data and blood test indexes were collected, and the ROC curve determined the optimal cut-off value. Kaplan-Meier survival curve and Cox regression model was used to analyze the effect of different levels of dNLR,LDH,LNI (dNLR combined with LDH index) before and after T-DM1 treatment on the survival of patients. Results The median PFS and OS of the patients with advanced HER2 positive breast cancer who received T-DM1 treatment were 6.9 months and 22.2 months, respectively. The optimal cut-off value of LDH and dNLR before T-DM1 treatment was 244 U / L (P = 0.003) and 1.985 (P = 0.013), respectively. Higher LDH and dNLR were significantly correlated with shorter median PFS and OS (P < 0.05). The median PFS of patients with LNI (0), LNI (1) and LNI (2) were 8.1 months, 5.5 months and 2.3 months, respectively, P = 0.007. Univariate and multivariate analysis showed that LDH > 244 U / L, dNLR > 1.985, LNI > 0, ECOG ≥1 and HER-2 (IHC2 +, FISH+) before the T-DM1 treatment were the poor prognostic factors. LDH uptrend after the T-DM1 treatment also predicted poor prognosis. Conclusion Serum LDH > 244 U / L and dNLR > 1.985 before the T-DM1 treatment were prognostic risk factors for patients with advanced HER2 positive breast cancer receiving T-DM1 treatment. The higher LNI score was significantly associated with shorter PFS and OS. LDH uptrend after T-DM1 treatment was also related to the poor prognosis.

Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs

During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of novel agents, such as new antibody-drug conjugates (ADCs). The latter are a group of drugs that benefit from the potency of cytotoxic agents whose action is specifically guided to the tumor by the target-specific antibody. Two anti-HER2 ADCs have reached the clinic: trastuzumab-emtansine and, more recently, trastuzumab-deruxtecan. In addition, several other HER2-targeted ADCs are in preclinical or clinical development, some of them with promising signs of activity. In the present review, the structure, mechanism of action, and potential resistance to all these ADCs will be described. Specific attention will be given to discussing novel strategies to circumvent resistance to ADCs.

Pneumonitis associated with Trastuzumab emtansine in a patient with metastatic breast cancer

Introduction Trastuzumab emtansine (TDM-1) is an antibody–drug conjugate effective in human epidermal growth factor receptor-2 - expressing advanced breast cancer. Pulmonary complications of TDM-1 are rarely reported. TDM-1-associated interstitial lung disease is referred to as pneumonitis. Case report A 47-year-old female patient who underwent modified radical mastectomy and axillary lymph node dissection operations due to a palpable mass in the right breast and axillary region. The patient who had received multiple chemotherapy was last receiving TDM-1 treatment. Fatigue, dyspnea, and tachypnea were detected for the first time on 20 days after the 6th treatment. Menagement and outcome In our case, we first considered metastasis, pneumonia and fungal infection based on radiological findings, but the lack of response to the treatments and the results of the investigations suggested drug-induced pneumonia and steroid treatment was started. Our case had a complete radiological recovery and complete response to sterod therapy. In such cases, it is important to first exclude infections and metastasis. In cases of drug-induced pneumonia, the first treatment option is systemic corticosteroids and generally responded well. Discussion Unlike other cases of interstitial pneumonia, lung imaging of our case was resembling a metastasis, pneumonia and fungal infection. With increasing use of TDM-1, we will have more experience in both efficacy and complications of TDM-1. Although TDM-1 is a well-tolerated drug, clinicians should be aware of rare pulmonary complications and prepared to respond appropriately.

Role of Post-Neoadjuvant therapy with trastuzumab emtansine in HER2-positive breast cancer

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study

PURPOSE We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). METHODS The phase III KAITLIN study ( NCT01966471 ) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor–negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing. RESULTS The median follow-up was 57.1 months (interquartile range 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80). CONCLUSION The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.