Sequencing Sacituzumab and Other Drugs in HR+, HER2- Breast Cancer

Stephanie L. Graff, MD (Moderator)

Director of Breast Oncology

Lifespan Cancer Institute

Providence, RI

CASE SUMMARY

• A 52-year-old, postmenopausal fitness instructor presents with a palpable mass in the upper, outer quadrant of her right breast, without apparent axillary involvement.

Medical/Social History

• Two pregnancies and 2 deliveries after 24 weeks
• Menopause: age 48 years
• No chronic comorbidities
• No concomitant prescription medications
• Most recent, negative mammogram: age 42
• Never smoker

Initial Diagnostic and Surgical Procedures

• ECOG performance status: 0 ​
• Diagnostic mammogram: high density mass with irregular margins and segmental microcalcifications
• Breast ultrasound: opaque, irregular, 34-mm mass with spiculated margins visualized at 3 o’clock in the right breast
• Core biopsy: estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2-negative ​grade 2 invasive ductal carcinoma (IDC); Ki-67 24%
• Lumpectomy and sentinel lymph node (SLN) biopsy: 38 mm, grade 2 IDC, no evidence of micrometastasis or isolated tumor cells from 2 SLNs on immunohistochemistry (IHC)
• RT-PCR 21-gene recurrence score: 27
• Staging: T2N0M0
• Adjuvant therapy:
  • Docetaxel/cyclophosphamide
  • Letrozole (Femara) for 5 years

Three Years After Completing Letrozole

• The patient presented with persistent low-back pain and fatigue, which restricts vigorous, prolonged exercise.

Follow-Up Diagnostic Tests

• ECOG performance status: 0 ​
• Complete blood count and differential: hemoglobin, 9.8 g/dL; all other indices within normal limits
• [18F] FDG PET/CT: avid radiotracer uptake detected in L4-L5 vertebrae and right pubic bone
• Biopsy of L4 bone lesion: malignant cytokeratin positive cells consistent with primary breast adenocarcinoma
  • ER/PR-positive, HER2 IHC 0
• Restaging:T2N0M1b (metastatic)

First-Line Therapy: CDK4/6 Inhibitor + Aromatase Inhibitor

• Patient had initial partial response, but after 16 months, showed evidence of disease progression new areas of bone involvement in T-spine, left ribs, and L2.
• Patient has ESR-wild type, no actionable mutation in PIK3CA, PTEN, or AKT, and no germline BRCA mutation.

DISCUSSION QUESTIONS

• How would you sequence an antibody-drug conjugate (ADC) in your treatment approach for this patient with advanced or metastatic hormone receptor (HR)–positive, HER2 0 breast cancer?
• When would you consider sacituzumab govitecan (Trodelvy) as second-linetherapy for a patient such as this?
• Would you consider sacituzumab govitecan in lieu oftrastuzumab deruxtecan (Enhertu; T-DXd) if the patient’s disease was HER2-low?

STEPHANIE L. GRAFF, MD: How are you sequencing ADCs in your treatment of advanced or metastatic HR-positive HER2 0 breast cancer? When are you considering it in second line vs third line? If this patient were HER2 low, how are you considering it and comparing it to T-DXd?

ANKUR MEHTA, MD: About [if the patient had] HER2-low disease, I would choose T-DXd before sacituzumab. In terms of the HER2 0 after the second biopsy, the algorithm would be either capecitabine prior to going on to sacituzumab. In the event the patient has not seen any prior chemotherapy or taxanes in the adjuvant setting and if they don't have any issues, then I have sometimes used eribulin [Halaven] ahead, depending on the volume of disease.

ERIN DAUCHY, DO: Granted, I am still fairly new in my practice, but a lot of times in the early metastatic setting, my patients are still eager to stay on oral therapy for as long as they can. Usually I'll do capecitabine first and at least the patients who did not have de novo metastatic disease usually had seen a taxane and some of them still have neuropathy, so I try to save those for later on. What I've seen so far in my practice is eventually a lot of these ER-positive patients develop visceral compromise, and I have the taxane in my back pocket for that.

BARBARA S. CIVIELLO, MD: I agree with what people have said so far. I think with individual patients, it tends to be a discussion point. I would use T-DXd before sacituzumab. Also for sequencing, if I wasn't worried about significant risk of pneumonitis in a patient, I would use it before sacituzumab. With the payloads being similar, there's still the question of can you use them one after another? It's a discussion with oral therapies; people don't typically want to be in clinic very long. I have more fatigue with my patients receiving sacituzumab than I do with my patients receiving T-DXd, so I think it's a discussion among many good options.

GRAFF: I'm surprised that you don't have as much fatigue; I feel like fatigue is my number one T-DXd adverse event.

CIVIELLO: I don't know why. I was fearful of pneumonitis, but I have quite a number of patients on T-DXd and they're tolerating it well, and I know that there is fatigue listed as an adverse event, but it just has not been what my patients are experiencing.

MARK SHPARBER, MD: If your patient has never seen doxorubicin [Adriamycin], it's a wonderful drug. It works very well in HR-positive patients. I know we have these million-dollar drugs and they're all very fancy, but an old-fashioned drug like doxorubicin works very well if the patient has not seen it in the past.

GRAFF: I completely agree. I am not afraid to give doxorubicin in HR-positive breast cancer. I'm surprised how often that is the recommendation that patients have when they come to me for second opinions, because I feel like a lot of the times when I see a second opinion, I'm seeing them in [very late stages, like the] eighth line, and that's the drug they haven't had yet. It boggles my mind every time.