Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses de-escalation strategies for patients with HER2-positive breast cancer.

In addition to a potentially shorter duration of trastuzumab (Herceptin), other strategies that have been evaluated include looking at less toxic regimens, says Murthy. For example, it has been shown that patients with node-negative, HER2-positive breast cancer benefit from paclitaxel and trastuzumab in the adjuvant setting. Additionally, the KRISTINE study randomized patients to docetaxel, carboplatin, trastuzumab, and pertuzumab (Perjeta) versus T-DM1 (ado-trastuzumab emtansine; Kadcyla) plus pertuzumab. Although the chemotherapy-containing arm did better in terms of pathological complete response, patients who did not receive chemotherapy still had a robust pathological response and seemed to benefit from a toxicity profile perspective, states Murthy.

However, physicians need to gain a better understanding of who can benefit from a chemotherapy-free regimen. Though chemotherapy-free regimens have yet to be established as a standard of care, it is an area worth exploring, notes Murthy.

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Dr. Murthy on De-Escalation Strategies in HER2-Positive Breast Cancer

Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses dual HER2 blockade in HER2-positive breast cancer.

Patients who have early-stage HER2-positive breast cancer with a tumor size greater than 2 cm or node-positive disease are currently treated with neoadjuvant trastuzumab (Herceptin), pertuzumab (Perjeta), and chemotherapy. This regimen is based on 2 phase II trials, NeoSphere and TRYPHAENA, explains Murthy. Both studies showed an improvement in pathological complete response when dual HER2-targeted therapy was combined with taxane-based chemotherapy compared with single HER2-targeted therapy alone.

Additionally, the results of the APHINITY trial showed a benefit, though small, in disease-free survival in the adjuvant setting. Since December 2017, pertuzumab has been FDA approved in the adjuvant setting. This calls into question which patients benefit from receiving adjuvant trastuzumab and pertuzumab for the duration of 1 year, says Murthy. Biomarkers will help physicians answer this question, though none have been identified to date. Therefore, the decision rests on clinical judgement and patient comorbidities, says Murthy.

Dr. Murthy on Dual HER2 Blockade in HER2+ Breast Cancer

Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the future of tucatinib in the treatment of patients with HER2-positive breast cancer. She presented phase Ib data at the 2018 ASCO Annual Meeting.

There is an ongoing phase II registration study testing tucatinib in patients with HER2-positive disease with or without brain metastases. Patients were randomized to either trastuzumab (Herceptin) and capecitabine or the combination plus tucatinib. Based on the results of the trial, tucatinib could potentially be granted FDA approval in the near future for third-line treatment of patients with HER2-positive metastatic breast cancer who have had prior treatment of trastuzumab, pertuzumab (Perjeta) and ado-trastuzumab emtansine (TDM-1; Kadcyla), Murthy says.

Another feature of the ongoing study is continuing the concept that patients with isolated brain progression should continue treatment after central nervous system-directed therapy.

Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the future of tucatinib in HER2-positive breast cancer.

Dr. Murthy on Future of Tucatinib in HER2+ Breast Cancer

Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses caveats of the PERSEPHONE trial.

Historically, the pivotal adjuvant trials have established 1 year of trastuzumab (Herceptin) as the standard of care in patients with HER2-positive breast cancer. The PERSEPHONE trial was a randomized phase III study that looked at the optimal duration of adjuvant trastuzumab. Over 4,000 patients were enrolled. The trial met its primary endpoint of disease-free survival at 4 years and demonstrated noninferiority with 6 months of adjuvant trastuzumab.

However, Murthy states that it is important to consider the patient population in interpreting the results of the trial. Patients enrolled in the trial did not necessarily receive trastuzumab concurrently with chemotherapy. Approximately 50% of patients received sequential trastuzumab which is not the current standard of care, explains Murthy.

Additionally, high-risk patients did not receive dual HER2-targeted therapy. The chemotherapy backbone was such that not every patient received anthracyclines and taxane chemotherapy. Some patients received taxane-based or anthracycline-based chemotherapy alone.

Rashmi K. Murthy, MD

Articles

Dr. Murthy on De-Escalation Strategies in HER2-Positive Breast Cancer

Dr. Murthy on Dual HER2 Blockade in HER2+ Breast Cancer

Dr. Murthy on Future of Tucatinib in HER2+ Breast Cancer

Dr. Murthy on Caveats of the PERSEPHONE Trial in Breast Cancer