Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease

Abstract

Background: Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation. Objectives: To evaluate the efficacy of the combined HER2-targeted agents, trastuzumab and lapatinib, as maintenance therapy in one patient. Methods: We describe a patient with HER2+, hormone receptor-negative, inflammatory metastatic breast cancer who was previously treated with doxorubicin, cyclophosphamide, and zoledronic acid followed by paclitaxel and trastuzumab. After completion, the patient underwent a bilateral mastectomy and then enrolled into a Phase III open-label clinical trial of trastuzumab plus lapatinib. Results: The patient experienced long-term stable disease on combined lapatinib and trastuzumab maintenance therapy over 4 years. Conclusions: This case demonstrates that prolonged stable disease is possible with lapatinib plus trastuzumab, even in patients with the aggressive inflammatory subtype. Optimization of maintenance therapy could improve outcomes for patients with HER2+ metastatic breast cancer.

Literature-Wide Association Studies (LWAS) for a Rare Disease: Drug Repurposing for Inflammatory Breast Cancer

“…Nineteen (19) of them have PubMed support, meaning they were studied in various IBC models according to PubMed publications. Eleven (11) of the 24 drugs with different mechanisms of action had been tested in clinical trials with varying degrees of clinical benefits for IBC [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. This indicates that our prediction has literature support.…”

“…Among the 24 predicted drugs, 19 of them ( Table 3 ) have PubMed support, i.e., they were studied in various IBC models. Eleven of the 24 drugs with different mechanisms of action (DNA damage, neuronal signaling, protein tyrosine kinase, and cytoskeletal signaling) have been tested in clinical trials with varying degrees of clinical benefits for IBC [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. A number of studies have been conducted to identify the best agents to use for neoadjuvant chemotherapy in IBC and the findings as of 2015 are summarized in [ 38 ].…”

Early relapse of inflammatory breast carcinoma treated with lapatinib and capecitabine: Ten years of complete response

“…In another case, double blockade with lapatinib and trastuzumab has been reported to be as effective as maintenance therapy in stage IV IBC, after initial treatment with chemotherapy and trastuzumab combination. The patient achieved stable metastatic disease during four years, and she is still in treatment …”

“…Lapatinib is an oral drug that inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1 (EGFR) and has demonstrated clinical activity in trastuzumab‐refractory states . Lapatinib has also shown clinical activity in IBC, but evidence in this field is scarce …”

Emerging Biomarkers and Targeted Therapies in Feline Mammary Carcinoma

“…Trastuzumab also acts synergistically with lapatinib revealing an additive antiproliferative effect in FMC cell lines [ 11 ]. In fact, this protocol has already proved effective against HBC, particularly for HER2-positive and metastatic therapy, improving patients DFS [ 126 , 138 ].…”