Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Women’s Cancers; director of Clinical Trials, Breast Oncology; senior physician at Dana-Farber Cancer Institute; and assistant professor of medicine at Harvard Medical School, discusses the unmet need with regard to effectively preventing central nervous system (CNS) recurrence in HER2-positive breast cancer.

In the early disease setting, the field continues to do a better job of curing patients with HER2-positive disease, with the addition of pertuzumab (Perjeta), T-DM1 (ado-trastuzumab emtansine; Kadcyla), and sometimes neratinib (Nerlyx), says Tolaney. However, despite these advances, some patients still recur after these treatments. Interestingly, in the phase 3 KATHERINE study, 5% of disease-free survival events observed were CNS recurrences, notes Tolaney. In fact, no benefit with T-DM1 over trastuzumab was observed with regard to preventing those recurrences.

The field is left with the unmet need of trying to decrease CNS recurrences, and it begs the question of how that need can be addressed. Some have hypothesized that using a TKI, such as tucatinib (Tukysa), could potentially address this need, based on the activity observed with the agent in the metastatic setting, says Tolaney.

To this end, an arm in the COMPASS trial is enrolling patients with residual disease after preoperative HER2-directed therapy and randomizing them to receive T-DM1 or T-DM1 with tuctanib. It will be interesting to know whether the addition of tucatinib will help improve overall events and decrease rates of CNS recurrence in patients with HER2-positive disease, concludes Tolaney.

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Sara M. Tolaney, MD, MPH, discusses the unmet need with regard to effectively preventing central nervous system recurrence in HER2-positive breast cancer.

Dr. Tolaney on CNS Recurrence in HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Women’s Cancers; director of Clinical Trials, Breast Oncology; senior physician at Dana-Farber Cancer Institute; and assistant professor of medicine at Harvard Medical School, discusses the unmet need with regard to effectively preventing central nervous system (CNS) recurrence in HER2-positive breast cancer.

In the early disease setting, the field continues to do a better job of curing patients with HER2-positive disease, with the addition of pertuzumab (Perjeta), T-DM1 (ado-trastuzumab emtansine; Kadcyla), and sometimes neratinib (Nerlyx), says Tolaney. However, despite these advances, some patients still recur after these treatments. Interestingly, in the phase 3 KATHERINE study, 5% of disease-free survival events observed were CNS recurrences, notes Tolaney. In fact, no benefit with T-DM1 over trastuzumab was observed with regard to preventing those recurrences.

The field is left with the unmet need of trying to decrease CNS recurrences, and it begs the question of how that need can be addressed. Some have hypothesized that using a TKI, such as tucatinib (Tukysa), could potentially address this need, based on the activity observed with the agent in the metastatic setting, says Tolaney.

To this end, an arm in the COMPASS trial is enrolling patients with residual disease after preoperative HER2-directed therapy and randomizing them to receive T-DM1 or T-DM1 with tuctanib. It will be interesting to know whether the addition of tucatinib will help improve overall events and decrease rates of CNS recurrence in patients with HER2-positive disease, concludes Tolaney.

Sara M. Tolaney, MD, MPH, discusses the unmet need with regard to effectively preventing central nervous system recurrence in HER2-positive breast cancer.

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith’s Center for Women’s Cancers, director of Clinical Trials, Breast Oncology, senior physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses sequencing strategies in metastatic HER2-positive breast cancer.

On December 20 2019, the FDA granted an accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201; Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti—HER2-based regimens in the metastatic setting.

More recently, on April 17 2020, the FDA approved tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for the same patient population who have received at least 1 prior anti—HER2-based therapy in the metastatic setting. The approval, which is based on data from the phase 2 HER2CLIMB trial, is also indicated for patients with brain metastases.

Both regimens can be considered for patients who received prior docetaxel, trastuzumab, and pertuzumab (Perjeta) in the frontline setting and ado-trastuzumab emtansine (T-DM1; Kadcyla) in the second-line setting, says Tolaney.

Patients with brain metastases should receive the tucatinib-based regimen, explains Tolaney. Unlike the phase 2 HER2CLIMB trial which included patients with progressive or untreated brain metastases, the phase 2 DESTINY-Breast01 trial with trastuzumab deruxtecan limited enrollment to a small number of patients with stable and treated brain metastases, explains Tolaney.

If patients progress on either third-line option, the alternative regimen can be implemented as a fourth-line therapy, concludes Tolaney.

Sara M. Tolaney, MD, MPH, discusses sequencing strategies in metastatic HER2-positive breast cancer.

Dr. Tolaney on Sequencing Strategies in Metastatic HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Women’s Cancers; director of Clinical Trials, Breast Oncology; senior physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses remaining questions with CDK4/6 inhibitors in hormone receptor (HR)—positive, HER2-negative metastatic breast cancer.

One major questions with CDK4/6 inhibitors that has arisen is whether there are major differences in outcomes between patients who receive chemotherapy compared with those who receive endocrine therapy plus CDK4/6 inhibition. Some data from the Young-PEARL trial were presented at the 2019 ASCO Annual Meeting and offered some insight, says Tolaney.

In the phase 2 trial, investigators enrolled premenopausal patients with HR-positive, HER2-negative metastatic breast cancer who progressed on prior tamoxifen. These patients were randomized to receive either aromatase inhibition and palbociclib (Ibrance) or capecitabine. At a median follow-up of 14 months, the median progression-free survival was 19.0 months in the endocrine with palbociclib arm versus 11.3 months in the capecitabine arm. The trial demonstrated that CDK4/6 inhibition is a very effective approach for this patient population and is likely superior to chemotherapy, concludes Tolaney.

Sara M. Tolaney, MD, MPH, discusses remaining questions with CDK4/6 inhibitors in hormone receptor–positive, HER2-negative metastatic breast cancer.
 

Author | Sara M. Tolaney, MD, MPH

Articles

Dr. Tolaney on CNS Recurrence in HER2+ Breast Cancer

Dr. Tolaney on CNS Recurrence in HER2+ Breast Cancer

Dr. Tolaney on Sequencing Strategies in Metastatic HER2+ Breast Cancer

Dr. Tolaney on Remaining Questions With CDK4/6 Inhibitors in HR+/HER2- Breast Cancer