Pluard Discusses Dosing of ADCs in HR+, HER2- Breast Cancer

CASE SUMMARY

• A 60-year-old woman with a history of locally advanced estrogen receptor (ER)– and progesterone receptor (PR)–positive, HER2-nonamplified disease (immunohistochemistry score of 1+, fluorescence in situ hybridization [FISH] negative) had invasive ductal carcinoma and high genomic risk (Oncotype DX recurrence score of 35).
• She was treated with surgery and adjuvant dose-dense chemotherapy, followed by aromatase inhibitor therapy for 10 years.

Two Years After Completing Adjuvant Therapy

• The patient presented with persistent rib pain.
• Fludeoxyglucose (FDG) 18F PET/CT scan demonstrated multiple FDG-avid lytic osseous metastases and suspicious-appearing, FDG-avid intrathoracic and intra-abdominal lymph nodes.
• Results from a pelvic lymph node biopsy demonstrated adenocarcinoma consistent with her primary breast cancer: ER 80%, PR 20%, HER2 0%.
• The patient was treated with first-line letrozole and ribociclib (Kisqali).

After 16 Months on Treatment

• The patient developed disease progression with enlarging and new involvement of intrathoracic and intra-abdominal lymph nodes.
• Next-generation sequencing (NGS) detected a pathogenic hot spot mutation in PIK3CA and no other alterations.
• Treatment was changed to second-line fulvestrant plus alpelisib.

After 10 Months on Treatment

• Disease progressed further with new lytic bone metastases and a new liver lesion.
• Biopsy report of liver specimen reported ER 60%, PR 0%, HER2 0%.
• NGS revealed no new mutations.
• Treatment was changed to third-line capecitabine.

After 8 Months on Treatment

• The patient developed disease progression with enlarging lymph nodes and enlarging liver metastasis.
• Liquid biopsy results showed detectable circulating tumor DNA (ctDNA) but no new mutations.
• Treatment was initiated with sacituzumab govitecan [Trodelvy] per National Comprehensive Cancer Network guidelines.

DISCUSSION QUESTIONS

• Share your insights and perspectives on the use of sacituzumab govitecan in the clinical practice setting.
• In which patients would you consider this treatment approach?

TIMOTHY J. PLUARD, MD: Is anyone not doing sequential antibody-drug conjugates [ADCs] and giving intravenous chemotherapy?

STEPHAN B. ROSENFELD, MD: I've never done it, but it certainly would be reasonable to do. It's a different mechanism of action and I think these are the 2 best single-agent chemotherapy drugs for patients with breast cancer [using sacituzumab and trastuzumab deruxtecan (T-DXd)] and you have to use them based on the HER2 status in my opinion.

PLUARD: Are you implying that you go T-DXd first if they are HER2 low?

ROSENFELD: I would, yes. I also think the diarrhea you have to pay attention to, but it's a pretty well-tolerated regimen with the dosing and the intervals. I've used it a handful of times, and I like it.

PLUARD: I'm curious about growth factor support. Are you prophylactically using granulocyte-colony stimulating factor [GCSF] in these cases? Are there patients you would particularly use GCSF support in?

ROSENFELD: I haven't prophylactically [given GCSF], but I have when it was needed.

BASSAM I. MATTAR, MD: Not the first cycle prophylactically but if they need it, then we'll become prophylactic.

PLUARD: Are you using short-acting GCSF or is anybody using PD-Lasta?

ROSENFELD: I've not used the long-acting GCSF, no.

PLUARD: Is everybody starting at 10 mg/kg full dose? Is anybody preemptively dose reducing?

ROSENFELD: I've dose reduced a few times just based on the fear of the diarrhea in the patients I can think of that we're frail and had quite a few comorbid conditions. I didn't want to put them in the hospital with dehydration, so I dose reduced on those instances.

YIFAN TU, MD: I usually do every 2 weeks to have the space for [pegfilgrastim] and all that.

PLUARD: So, you're dosing every other week and using pegfilgrastim after each dose. I've heard others shifting to that schedule.

MARK W. KARWAL, MD: I don't even how many ADCs we have now. One for myeloma was pulled [from the] market, but it was 10 maybe, but they're all given once every 3 weeks—IgG is a long half-life molecule—so I don't know why sacituzumab is [given on] day 1 and day 8. I think if day 8 becomes a problem, you just skip it and go every 3 weeks like all the other ones. It's metastatic disease; you don't have [to overburden the patient].