Yara Abdou, MD, assistant professor, Division of Oncology, Lineberger Comprehensive Cancer Center, UNC Health, UNC School of Medicine, discusses the significance of the phase 3 DESTINY-Breast03 trial (NCT03529110) in HER2-positive breast cancer.

Data from DESTINY-Breast03 demonstrated fam-trastuzumab deruxtecan-nxki (Enhertu) elicited statistically significant and clinically meaningful improvements in progression-free survival (PFS) vs ado-trastuzumab emtansine (Kadcyla; T-DM1), Abdou says. Moreover, all subgroups received a significant benefit in PFS, including visceral disease, hormone receptor status, prior pertuzumab (Perjeta) use, and brain metastases, Abdou explains.

Although the data are not yet statistically significant, trastuzumab deruxtecan also produced an encouraging overall survival benefit, Abdou adds. These results support trastuzumab deruxtecan becoming the standard of care in the second-line setting for metastatic, HER2+ breast cancer, Abdou explains.

The trial generated reassuring safety data, and most of the interstitial lung disease events were grade 1 or 2, with only 2 grade 3 cases, and no grade 4 or 5 incidents, Abdou continues.

Trastuzumab deruxtecan led to a lower rate of intracranial progressive disease, compared with T-DM1, Abdou adds. Larger studies are still needed to examine the activity of trastuzumab deruxtecan in untreated and actively progressing brain metastases, Abdou says. Current evidence remains for tucatinib (Tukysa) combination as the standard-of-care option for patients with brain metastases, Abdou concludes.

Videos

Yara Abdou, MD, discusses the significance of the phase 3 DESTINY-Breast03 trial in HER2-positive breast cancer.

Dr. Abdou on the Significance of the DESTINY-Breast03 Trial in HER2-Positive Breast Cancer

Data from the following clinical trials are discussed:

+ breast cancer identifies recurrent pathway alterations associated with anti-HER2 resistance and new therapeutic vulnerabilities

GS1-05: Datopotamab deruxtecan (Dato-DXd) in advanced/metastatic HER2- breast cancer: results from the phase 1 TROPION-PanTumor01 study

GS04-09: Quality-of-life results from OlympiA: a phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after neoadjuvant chemotherapy in patients with germline 

After discussing a few more key datasets from the SABCS 2021 Virtual Meeting, expert panelists discuss how they would approach treatment in several subsets of breast cancer. 

SABCS 2021: Novel Approaches to Breast Cancer Management 

PD4-02: Safety and efficacy of a tucatinib-trastuzumab-capecitabine regimen for treatment of leptomeningeal metastasis in 

+ breast cancer: Results from TBCRC049, a phase 2 nonrandomized study

PD4-04: Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated 

+ metastatic breast cancer with brain metastases (HER2CLIMB)

P1-18-26: Intracranial efficacy of tucatinib, palbociclib, and letrozole combination in patients with HR+/

P1-21-03: Efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of patients with 

+ breast cancer with or without brain metastases: a systematic review and meta-analysis

OT1-13-01: HER2CLIMB-04: phase 2 trial of tucatinib + trastuzumab deruxtecan in patients with 

+ locally advanced or metastatic breast cancer with and without brain metastases

Focusing on datasets from the SABCS 2021 Virtual Meeting, panelists consider novel approaches to the management of brain metastases in breast cancer.

SABCS 2021: Brain Metastases Updates in Breast Cancer 

GS3-01: Trastuzumab deruxtecan (T-DXd; DS-8201a) vs trastuzumab emtansine (T-DM1) in patients with 

–positive metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINYBreast03

GS3-02: Updated overall survival (OS) results from the phase 3 PHOEBE trial pyrotinib vs lapatinib in combination with capecitabine in patients with 

GS4-10: Neratinib + fulvestrant + trastuzumab for hormone receptor (HR)–positive, HER2-mutant metastatic breast cancer and neratinib + trastuzumab for triple-negative disease: latest updates from the SUMMIT trial

P2-13-10: First-in-human HER2-targeted bispecific antibody KN026 for the treatment of patients with 

+ metastatic breast cancer: results from a phase I study

P2-13-07: Zanidatamab (ZW25), a HER2-targeted bispecific antibody, in combination with chemotherapy for 

+ breast cancer: results from a phase 1 study

PD8-07: Evaluation of tucatinib + paclitaxel + pertuzumab + trastuzumab followed by AC (doxorubicin hydrochloride, cyclophosphamide) in high-risk HER2+ stage II/III breast cancer: results from the I-SPY2 trial

Expert panelists share their perspectives on metastatic breast cancer management datasets from the SABCS 2021 Virtual Meeting. 

SABCS 2021: Updates in Metastatic Breast Cancer

I was 13 years old when I decided to become a doctor. At that age, I could not have guessed how challenging that path would be. Seven years of being immersed in textbooks, then 3 years of intensive internship and residency followed by a 3-year fellowship.

Now I am 30 years old and reminiscing about a life built on hard work and sacrifice. A sacrifice of my 20s, sleep, and even health. But apart from being able to prescribe medications, what has changed?

As soon as the title of MD is added to our names, expectations skyrocket, and anything less than perfection turns into a disappointment. We enter a world of tremendous internal and external pressures to flourish, and without knowing it, we join a malicious culture. A culture of toughness and boldness but also a culture where vulnerability is considered a weakness and any feelings of doubt or fear are buried. A culture that fuels our obsession with perfectionism and fosters unrealistic expectations. A culture that inevitably leads to emotional burnout. 

Despite our bravado, our confidence, and our skill, not everyone makes it. I lost a bright, compassionate, and caring colleague during residency. His suicide was a shock to everyone, including his family, because he was a cheerful doctor who had shown no signs of struggle or depression.

Doctors master the art of compartmentalization and disguise. The world sees us as superheroes. We expect to be superheroes. So how can we admit to fear or vulnerability? How can we acknowledge our weaknesses or confess to our exhaustion? How can we set aside our superhero masks without being judged or feeling shame?

The truth is that physicians are more than twice as likely to kill themselves as the rest of the population. Around 400 doctors in the United States commit suicide every year, more than 1 per day, a higher suicide rate than that of any other profession.

 And for every doctor who dies by suicide, thousands more contemplate the act. Good people are dying, friends of mine and friends of yours. It’s time for a change.

Our jobs can often lead to complete physical and mental exhaustion, yet our culture has taught us to suck it up and refuse to seek help. Oncology, in particular, is one of the most stressful medical specialties. It takes a great amount of physical and emotional energy to care for patients with terminal cancer. Watching patients deteriorate and suffer, in addition to repeatedly breaking bad news, can be emotionally draining.

Results of a qualitative study among oncologists showed that exposure to frequent patient death motivated clinicians to improve patient care (66.7%). However, it also led to exhaustion (62.0%), burnout (75.9%), and compartmentalization of feelings at work and home (69.6%).

Furthermore, we are expected to stay ahead of a constantly advancing field and novel treatment strategies, which is a challenge on its own.

So how do we deal with careers that often lead to complete physical and mental fatigue? We often hear the same suggestions: mindfulness classes, meditation, wellness retreats, resiliency training. These are great. However, doctors are resilient by nature. The problem is not our lack of resiliency; it’s numbness to our feelings. We see far too much pain to pretend as though it’s nothing. We need to be able to voice our worries and fears, share our vulnerabilities, connect with our feelings, and find comfort in our peers. It’s time to put an end to a culture that supports bravado and intolerance. Asking for help is 

Emotional resilience fluctuates over time, and recognizing when this resilience is wearing away is important. Acknowledging our feelings is the first step toward a healthier state of well-being. We can start by simply asking ourselves at the end of each day, “What are the 3 most difficult things I had to deal with today?” Once we are comfortable with identifying our own feelings, we then become capable of sharing these feelings with friends and colleagues.

Talking about those stressors is an important step in fighting burnout. A study done at the Mayo Clinic found that giving physicians time to spend with their colleagues in small groups for private discussions provided them with mutual support to deal with challenges, resulting in lower burnout, greater well-being, and improved job satisfaction.

A shout-out to all my friends and colleagues in residency and fellowship who helped me become the resilient physician I am today. It is vital to encourage community at work and cultivate an environment of collegiality and support.

We all go through a similar path of struggles and challenges, so why not share our fears with one another? Pamela Wible, MD, is a family physician in Eugene, Oregon, who has worked to combat physician suicide and burnout since 2005 and encourages healthcare providers to defend and protect one another. As she put it in a 2015 Ted Talk, “If we all shine our lights together, then there is no darkness to fear.”

Being a physician is not just a job, it’s a calling—a calling to be that superhero who saves lives. We have chosen a long and difficult path filled with ongoing daily sacrifices, yet we take pride in the work we do. Nonetheless, it is crucial to recognize that everyone experiences burnout, even superheroes.

There is no higher calling than being able to help people in need and alleviate suffering. However, we can’t give patients care that we have never received. Therefore, let us care for ourselves, and care for one another. Only then we can fulfill our calling and be true superheroes for our patients.

Yara Abdou, MD, is a clinical hematology/oncology fellow at the Roswell Park Comprehensive Cancer Center.

Medscape national physician burnout, depression & suicide report 2019. Medscape website. medscape.com/slideshow/2019-lifestyle-burnout-depression-6011056. Accessed April 4, 2019.

Granek L, Ariad S, Nakash O, et al. Mixed-methods study of the impact of chronic patient death on oncologists’ personal and professional lives. 

. 2017;13(1):e1-e10. doi: 10.1200/JOP.2016.014746.

Wible P. Why doctors kill themselves. TEDMED website. bit.ly/2YsyUEO. Accessed April 26, 2019.

Articles

Yara Abdou, MD, sheds light on the challenging path of becoming an oncologist.

Yara Abdou, MD

Articles

Dr. Abdou on the Significance of the DESTINY-Breast03 Trial in HER2-Positive Breast Cancer

SABCS 2021: Novel Approaches to Breast Cancer Management

SABCS 2021: Brain Metastases Updates in Breast Cancer

SABCS 2021: Updates in Metastatic Breast Cancer

Even Superheroes Can Burn Out in Oncology