Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial

Robidoux, André; Tang, Gong; Rastogi, Priya; Geyer, Charles E.; Azar, Catherine A.; Atkins, James N.; Fehrenbacher, Louis; Bear, Harry D.; Baez-Diaz, Louis; Sarwar, Shakir; Margolese, Richard G.; Farrar, William B.; Brufsky, Adam; Shibata, Henry R.; Bandos, Hanna; Paik, Soonmyung; Costantino, Joseph P.; Swain, Sandra M.; Mamounas, Eleftherios P.; Wolmark, Norman

doi:10.1016/s1470-2045(13)70411-x

Cited by 341 publications

(298 citation statements)

References 29 publications

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“…Subgroup analysis of the data from the NeoALTTO (20) and NeoSphere (21) trials showed that the pCR rate-related benefit was higher in HR-negative patients compared with HR-positive patients, regardless of the anti-HER2 therapy administered (lapatinib, trastuzumab, or a combination of the two). The same effect was observed in the NSABP B-41 trial (22) in which even higher pCR rates were achieved using the combination of weekly paclitaxel administration and targeted therapy (lapatinib, trastuzumab, or a combination of the two) following standard doxorubicin plus cyclophosphamide treatment (21).…”

Section: Discussionmentioning

confidence: 53%

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature

Kiba¹,

Morii²,

Takahashi³

et al. 2016

Oncology Letters

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Abstract. While tumor size, the presence of inflammatory carcinoma and lymph node involvement are the main prognostic factors of women with locally advanced breast cancer, the prognostic value of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status has not been fully clarified. The present study examined the therapeutic efficacy of a neoadjuvant fluorouracil, epirubicin and cyclophosphamide regimen (FEC), followed by weekly paclitaxel and/or trastuzumab administration, in the treatment of hormone receptor-negative breast cancer patients. Between April 2012 and February 2014, 14 patients with hormone receptor-negative local breast cancer (triple-negative type, 9 patients; HER2 type, 5 patients) were included in the study. In all cases, the histological type of the primary cancer was invasive ductal carcinoma. Among the 14 women who received the regimen, 5 presented with stage I cancer (35.7%), 3 with stage IIA (21.4%), 3 with stage IIB (21.4%), 1 with stage IIIB (7.1%) and 2 with stage IIIC (14.3%), according to the American Joint Committee on Cancer staging system. With regard to the tumor-node-metastasis classification, 5 patients were T1N0M0 (35.7%), 3 were T2N0M0 (21.4%), 3 were T2N1M0 (21.4%), 2 were T3N3M0 (14.3%) and 1 was T4N1M0 (7.1%). The pathological response was evaluated using resected tissue following neoadjuvant chemotherapy, according to the criteria established by the Japanese Breast Cancer Society. Patients were classified into pathological responders (grades 2 and 3, 71.4% of all patients) and non-responders (grade 1, 28.6% of all patients). A pathological complete response (pCR) was achieved in 50.0% of all cases (7/14); 44.4% of triple-negative-type cases (4/9) and 60.0% of HER2-type cases (3/5). Hematological and non-hematological toxicity was reversible and manageable. No patients withdrew from treatment, and favorable compliance was achieved. The present study demonstrated that neoadjuvant FEC followed by weekly administration of paclitaxel and/or trastuzumab induces a high pathological response and a high pCR rate in patients with hormone receptor-negative breast cancer. Due to the high clinical benefit rate and acceptable safety profile, this regimen should be considered an acceptable neoadjuvant treatment option for hormone receptor-negative breast cancer. IntroductionNeoadjuvant therapy is a standard treatment option for breast cancer (1). It has been suggested that taxane-based chemotherapy is closely associated with improved outcomes in hormone receptor-negative or human epidermal growth factor receptor 2 (HER2)-positive disease, and little, if any, benefit from taxane-based chemotherapy has been observed for the ≥50% of patients with hormone receptor-positive and HER2-negative disease (2).Paclitaxel is considered a fundamental drug in the treatment of breast cancer (3). As a potent mitotic inhibitor, it used as an effective chemotherapeutic agent in the treatment of solid tumors. A randomized phase III trial reported that paclitaxel...

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Section: Discussionmentioning

confidence: 53%

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature

Kiba¹,

Morii²,

Takahashi³

et al. 2016

Oncology Letters

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“…As expected the addition of lapatinib resulted in worse side effects, mainly related to diarrhea and rash. However, in contraposition to the NeoALLTO, the freshly published NSABP B-41 study showed no statistical difference with the combination of trastuzumab and lapatinib when compared to either drugs used as single agent [33] . Two issues though deserves further discussion.…”

Section: Neo-adjuvant Treatmentmentioning

confidence: 91%

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

Recondo¹

2014

WJCO

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During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, adotrastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 overexpressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available. Key words: Breast cancer; Human epidermal growth factor receptor-2; Trastuzumab; Pertuzumab; Adotrastuzumab; Lapatinib Core tip: This is a review manuscript with the most updated information regarding the state of the art management of human epidermal growth factor receptor-2 positive breast cancer. It summarizes the most relevant and updated information derived from more than 40 phase Ⅱ and Ⅲ clinical trials that constitute the theoretical framework to support our daily practice. It also highlights some key clinical concepts that should not be overlooked by critically appraising the current literature. Finally, it gives the reader with a compilation of potential new agents that are currently being tested and may soon become the next step in the battle against this disease.Recondo G Jr, Dìaz Canton E, de la Vega M, Greco M, Recondo G Sr, Valsecchi ME. Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions.

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“…Among all of the drugs that target HER2 and HER2 TK, trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1) and lapatinib have been proven to be effective in treating HER2 + BC in several clinical trials compared with chemotherapy drugs alone (17)(18)(19)(20). Trastuzumab, the first-generation targeted therapy drug, is a humanized monoclonal antibody targeting the extracellular domain of HER-2 (21,22) and has the ability to downregulate the signaling pathways involving PI3K/Akt and MAPK (23,24), which in turn inhibits the proliferation of BC cells that overexpress HER2.…”

Section: Current Targeted Therapy Drugsmentioning

confidence: 99%

“…Though the incidence of PFS, OS and overall response rate (ORr) are significantly promoted among HER2 + BC patients by treatment with HER2-targeting drugs (17)(18)(19), drug resistance and progression of metastatic breast cancer (MBC) still develop gradually and are detrimental to the prognosis of patients. It has been estimated that about half of HER2 + MBC does not respond to anti-HER2 drugs (28).…”

Section: Does Every Her2 + Bc Patient Benefit From Targeted Therapy?mentioning

confidence: 99%

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

et al. 2018

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Abstract.Human epidermal growth factor receptor-2 positive breast cancer (HER2 + BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2 + BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2 + BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2 + BC patients in the future.

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Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial

Cited by 341 publications

References 29 publications

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature

Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

Novel treatment strategies for patients with HER2‑positive breast cancer who do not benefit from current targeted therapy drugs (Review)

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