Early Lines of Therapy for HER2+ De Novo Metastatic Breast Cancer

Reshma L. Mahtani, DO:I would say that the treatment of HER2+ breast cancer is one of our greatest success stories in oncology. Starting with the approval of trastuzumab followed by several other agents that target HER2, we’ve dramatically improved survival for these patients.

In the first-line setting, this patient was treated with the CLEOPATRA regimen, which consists of a taxane, trastuzumab, and pertuzumab. This decision was based on really impressive improvements in progression-free survival and overall survival demonstrated by that study. I would comment that I would have probably tried to get approval of Abraxane [nab-paclitaxel] in this setting, just because she was diabetic and that would have afforded the opportunity to not give her steroids as a premedication. Second-line treatment with the antibody-drug conjugate trastuzumab emtansine [T-DM1] is also pretty standard based on the results of the EMILIA trial. So, I would say this patient’s treatment course was quite typical in the first- and second-line settings.

Many factors influence our treatment recommendations in the first- and second-line settings. In terms of how this patient was treated, I would say that many patients can receive treatment in the first-line setting with a taxane for about 4 to 6 months before toxicity issues start to become apparent. In this case, the treatment was stopped for neuropathy. In the situation where there’s an option to start hormonal therapy in ER+, HER2+ patients, this is usually done. This patient didn’t have that opportunity because she had ER⁻ disease.

Our decisions in this setting are informed by what treatments patients received in the adjuvant setting, any persistent toxicities from those treatments, disease burden and, of course, patient preference. In this case, because the patient had de novo metastatic disease and was symptomatic with pain, she didn’t have the option for hormonal therapy in conjunction with HER2-targeted treatment. I would say the decision making was pretty straightforward in this case.

In terms of what’s coming, there are several important studies that may change what we do in the first- and second-line settings. For example, in the second-line setting, there’s an ongoing trial looking at trastuzumab deruxtecan [DS-8201] versus T-DM1. In the first-line setting, there is a study that’s ongoing by NRG Oncology looking at the addition of immunotherapy in combination with a taxane, trastuzumab, and pertuzumab. Of course, these are ongoing studies that have not reported out yet, so our first- and second-line treatments are pretty standardized at this juncture.

Transcript edited for clarity.

Case: A 59-Year-Old Woman WithHER2+ De Novo Metastatic Breast Cancer

Initial presentation

  • A 59-year-old, postmenopausal woman presented to her PCP for an annual physical exam, she was referred to undergo screening mammography; she reported back and hip pain along with occasional headaches
  • PMHx: diabetes, medically controlled
  • OB/GYNHx: nulliparous
  • FHx: no family history of cancer
  • PE: obese, palpable left breast mass with axillary adenopathy

Clinical workup

  • Labs: alkaline phosphatase 230 IU/L (normal range 20-140 IU/L); otherwise WNL
  • Breast imaging revealed a 2.1 cm irregular appearing mass in the left breast with suspicious axillary adenopathy
  • Ultrasound-guided core biopsy of the left breast mass and axillary node confirmed high-grade infiltrative ductal carcinoma; ER-, PR-,HER2,3+ by IHC
  • Brain MRI was negative
  • PET/CT and bone scan revealed multiple lesions in the spine and pelvis; and several pulmonary nodules; pulmonary nodule biopsy revealed invasive ductal carcinoma; ER-,HER2+
  • ECOG PS 1

Treatment and Follow-Up

  • She was started on paclitaxel + trastuzumab + pertuzumab and completed 6 months of chemotherapy at which point paclitaxel was discontinued due to worsening neuropathy; trastuzumab and pertuzumab were continued
  • Follow-up imaging at 3 months showed no FDG activity in the bones or lungs; bone pain resolved
    • Denosumab was started to reduce skeletal related events
  • Further follow-up imaging showed stable disease until 18 months when she developed worsening cough; imaging showed progressive bone disease and multiple new pulmonary nodules
    • Trastuzumab emtansine (T-DM1) was started
  • Follow-up imaging showed response to treatment which lasted for ~ 9 months
    • She developed headaches, and increasing bone pain
  • Brain MRI at that time showed 3 lesions, all < 2-cm; she was treated with SRS (stereotactic radio surgery)
    • Bone scan showed progressive bone metastases
  • Initiated neratinib 240 mg (6 tablets) PO QD + capecitabine
    • She was started on prophylactic loperamide
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