John Crown, MB, BCh, BAO, BSc, MD, MBA, professor, University College Dublin, Dublin City University, consultant medical oncologist, St. Vincent’s Private Hospital, chairman, Molecular Therapeutics, Cancer Ireland, Dublin, Ireland, discusses the rationale for evaluating lapatinib (Tykerb) with standard trastuzumab/chemotherapy regimen in patients with HER2-positive breast cancer, as well ascontextualizes results from a phase 2 trial (NCT01485926).

The randomized, open-label, multi-arm trial was designed to assess the addition of lapatinib to a preoperative regimen of trastuzumab (Herceptin), docetaxel and carboplatin (TCHL) in patients with early-stage HER2-positive breast cancer. Based on a large body of preclinical data, investigators hypothesized that the investigation of the chemotherapy backbone could be beneficial due to its potential synergy and antitumor activity, Crown begins. These data also indicated that TCHL was not associated with a high risk of cardiac toxicity, unlike trastuzumab and anthracycline-containing regimens, Crown continues. Additionally, the administration of TCHL was potentially advantageous, as the maximum dosage level could be administered at the start of treatment, he says.

The study enrolled 76 patients who were assigned to receive docetaxel, carboplatin, and trastuzumab (TCH) or the regimen with the addition of lapatinib (TCHL). Patients then underwent surgery, followed by 1 year of adjuvant trastuzumab. The trial originally included a third arm of lapatinib monotherapy which was discontinued in light of data suggesting its inferiority to trastuzumab, Crown explains.

The trial demonstrated that TCHL did not elicit a superior pathological complete response (pCR) rate compared with TCH, with pCR rates of 51.6% and 52.8% respectively, Crown says. This negative result does not indicate that TCHL is an inferior regimen but suggests that TCH was more effective for this patient population than originally anticipated, he states.

Although the trial did not meet its primary end point of augmented pCR, long-term follow-up analysis demonstrated a statistically significant improvement in relapse-free survival with neoadjuvant lapatinib. Further investigation is needed to contextualize the results, as well as understand its implications for neoadjuvant treatment approaches, Crown concludes. 

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John Crown, MB, BCh, BAO, BSc, MD, MBA, discusses the rationale for evaluating lapatinib (Tykerb) with standard trastuzumab/chemotherapy regimen in patients with HER2-positive breast cancer, as well as contextualizes results from a phase 2 trial.

Dr. Crown on the Investigation of Lapatinib Plus Chemotherapy in HER2+ Breast Cancer

John Crown, BCh, BAO, BSc, MD, MBA, professor and consultant, medical oncology, St. Vincent’s Private Hospital, Dublin, Ireland, discusses the role of eribulin mesylate (Halaven) in triple-negative breast cancer.

Multiple randomized trials have established eribulin as an active treatment for patients with TNBC, Crown says.

Moreover, the drug provides an overall survival (OS) benefit compared with standard chemotherapy for heavily pretreated patients with metastatic disease, explains Crown. 

Notably, findings from a subgroup analysis of a phase 3 trial demonstrated superior OS with eribulin compared with capecitabine (Xeloda) among patients with HER2-negative tumors, including HER2-negative breast cancer and TNBC, Crown says. 

As such, eribulin appears to have established itself as a potent agent in the TNBC armamentarium, concludes Crown.

John Crown, BCh, BAO, BSc, MD, MBA, discusses the role of eribulin mesylate in triple-negative breast cancer.  



John Crown, BCh, BAO, BSc, MD, MBA

Articles

Dr. Crown on the Investigation of Lapatinib Plus Chemotherapy in HER2+ Breast Cancer

Dr. Crown on the Role of Eribulin Mesylate in TNBC