Megan May, PharmD, Gives Overview of Recent Breast Cancer Advances

Megan May, PharmD, assistant professor at the University of Kentucky College of Pharmacy in Lexington, Kentucky

As October is Breast Cancer Awareness Month, CancerNetwork^® spoke with Megan May, PharmD, assistant professor at the University of Kentucky College of Pharmacy in Lexington, Kentucky, about recent advances in breast cancer and how she plays a critical role as a member of the multidisciplinary team.

According to May, one of the biggest breakthroughs of 2022 in breast cancer occurred during the American Society of Clinical Oncology (ASCO) Annual Meeting with the presentation of the phase 3 DESTINY-Breast04 trial (NCT03734029).¹ This trial investigated the use of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) vs physician’s choice chemotherapy in patients with HER2-low advanced breast cancer. In August 2022, the agent was approved for use in patients with unresectable or metastatic HER2-low breast cancer based on the results of this trial.²

As treatments are ever evolving for patients with breast cancer, May noted it remains crucial for clinicians to educate themselves about newly available therapies for their patients. Additionally, she highlights the need for diversity in clinical trials and which studies she’s most looking forward to seeing the results of.

CancerNetwork^®: What is your role as a multidisciplinary team member in the management of breast cancer?

May: Pharmacists have an in-depth understanding of medications and why adverse effects occur. My main job as a pharmacist is patient education. I’m able to explain to patients what to expect from certain treatments and how to manage these toxicities at home. For breast cancer specifically, we’re now prescribing patients both intravenous and oral agents. Within my practice, we have a pharmacist-led oral chemotherapy clinic. For every oral agent prescribed, my job is to ensure it’s for an appropriate indication by evaluating the labs to confirm the dosing is appropriate and [to help] manage any supportive care needs. Pharmacists can also assist the team by optimizing adherence and compliance for our patients who are receiving therapy, whether it’s an infusion or an oral agent. We must also manage financial toxicity for these patients, which a pharmacist can assist with alongside a financial navigator.

What has been the biggest breakthrough in breast cancer recently?

The biggest breakthrough this year has been on the data surrounding HER2-low breast cancer. This is from the DESTINY-Breast04 clinical trial. In this phase 3 trial, patients with metastatic breast cancer whose tumors had low levels of HER2 protein were given T-DXd, a HER2-specific antibody-drug conjugate. The drug lengthened progression-free survival and overall survival compared with standard chemotherapy. This is likely to become our new standard of care. Approximately 80% of breast cancers are HER2-negative, but researchers now recognize that 55% of all breast cancers may contain low levels of HER2 and these can be targeted with our HER2-directed therapies. The DESTINY-Breast04 trial results showed evidence that this is the case. Of the 557 patients who were enrolled, the median progression-free survival was 9.9 months with T-DXd compared with 5.1 months with a physician’s choice of chemotherapy [HR, 0.50; 95% CI, 0.40-0.63; P <.001]. The median overall survival in the total population was 23.4 months for the T-DXd arm compared with 16.8 months in the arm receiving standard chemotherapy [HR, 0.64; 95% CI, 0.49-0.84; P = .001]. This has the potential to improve survival for almost 50% of patients diagnosed with metastatic breast cancer today, and T-DXd is now FDA approved for adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or who have developed disease recurrence during or within 6 months of completing adjuvant treatment.

What are some of the biggest barrier to optimal care in patients with breast cancer?

Metastatic breast cancer clinical trials are hugely important. As we know, the findings from these trials inform future treatments and standards of care. One of our barriers is that African American women who are diagnosed with breast cancer only represent approximately 3% of clinical trial participants. The advances that we see with these results may not necessarily be relevant to this population. That’s why our clinical trials need to include a more diverse patient population. There [is an ongoing study called the] BECOME study, or the Black Experience of Clinical Trials and Opportunities for Meaningful Engagement.³ This is a survey that is a project of the Metastatic Breast Cancer Alliance and specifically examines barriers that preclude African American women from joining a clinical trial. A total of 40% of African American women said that their care team had not discussed trial enrollment compared with 33% of the non-African American respondents. From this study, the investigators do hope to incorporate steps into the clinical trial enrollment process to increase diversity in our clinical trials. They want to make sure we are enhancing clinical trial awareness. We’re building trust through clear communication to address any concerns patients might have about adverse effects, effectiveness [of treatment], and harm and fair treatment and are also helping our patients find and access these clinical trials.

What clinical trials are you excited to see the results of?

There are several clinical trials in the breast cancer space that have launched throughout 2022, and it leaves us a lot to look forward to in the new year. There’s 1 study evaluating patritumab deruxtecan, and this targets HER3-expressing metastatic breast cancer.⁴ HER3 is expressed in approximately 30% to 50% of breast cancers across subtypes. This study was a phase 1/2 study (NCT02980341) evaluating 182 patients who were heavily pretreated with hormone receptor–positive, HER2-negative, HER3-high or -low expressing metastatic breast cancer. These patients were randomized to different dosing. Patritumab deruxtecan showed clinically meaningful and durable anti-tumor activity across subtypes. There was a confirmed overall response rate of 30%. It also appears to have a manageable safety profile with 10% of patients discontinuing treatment due to treatment-emergent adverse events. There were 12 cases [6.6%] of interstitial lung disease though, so we need to look out for that as this drug moves to further studies.

What do you hope to see more of in the future management of patients with breast cancer?

New treatments and breakthroughs are still needed to end metastatic breast cancer. We’ve seen a lot of progress in this area, especially this year, and it’s continuing to accelerate in approvals for breast cancer. We need to continue with our research to discover and improve therapies for these patients.

References

1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
2. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. News Release. FDA. August 5, 2022. Accessed October 12, 2022. https://bit.ly/3VlOsIl
3. BECOME: Black Experience of Clinical Trials and Opportunities for Meaningful Engagement. Metastatic Breast Cancer Alliance. Accessed October 17, 2022. https://bit.ly/3EPI9ag
4. Krop IE, Masuda N, Mukohara T, et al. Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). J Clin Oncol. 2022;40(suppl 16):1002. doi:10.1200/JCO.2022.40.16_suppl.1002