Andrew Seidman, MD: Different Mechanisms of Action in Eribulin

How does eribulin differ in its mechanism of action from the other lines of therapy in this patient?

Eribulin, or Halaven, is an anti-microtubule classically, but we're learning more and more about the potential mechanisms of action. I was there in the early 1990s developing paclitaxel for breast cancer, and we know that the taxanes exert a unique effect on microtubules in that they cause polymerization of the microtubule and they stabilize the microtubules against the forces that cause their depolymerization. This is uniquely different than vinca alkaloids, which cause the depolymerization of the microtubules.

So we've learned that Halaven has a unique effect in preventing elongation at the end of the microtubule, it prevents the alpha and beta tubulent subunits from forming successful dimers, which are necessary for this process of elongation. This is an energy-dependent process and these dimers form dysfunctional aggregates, which can't contribute to that process.

Triple Negative Breast Cancer: Case 1

Christine H is a 54-year-old stay-at-home-mother who works part time as a real estate agent. Medical history is notable for hypertension (well controlled) and surgery for aortic aneurysm in 2011

In September 2013, she presented to her PCP with a right breast lump; mammogram showed a large primary breast mass and two enlarged axillary lymph nodes.

• She underwent an extent of disease evaluation, which consisted of a chest, abdomen, pelvis, and bone scan, which showed no evidence of distant metastases
• Ultrasound-guided core needle biopsy of the right breast mass revealed grade 3 invasive ductal carcinoma that was ER-, PgR-, and HER2- (triple-negative) with cytokeratin 5/6 staining and 50% Ki67 staining
• The patient proceeded to right breast mastectomy and axillary lymph node dissection in October 2013
• She had a 4.8cm invasive breast cancer and the axillary lymph node dissection showed 15 positive nodes
• She underwent adjuvant therapy with doxorubicin plus cyclophosphamide (4 cycles), followed up by paclitaxel (4 cycles) and post-mastectomy radiation

At her follow-up in May 2014, the patient showed progression of the right chest wall metastases, and several new liver lesions were detected.

• She underwent therapy with paclitaxel plus bevacizumab for 5 cycles and her disease stabilized

In December of 2014, she presented with increasing fatigue and chest pain on follow up and her CT scan was consistent with progression of the hepatic metastases, with several new lesions also noted in the lungs; her ECOG performance status (PS) at the time was 1.

• She underwent therapy with pegylated liposomal doxorubicin and had a partial response after 4 cycles of therapy. After 6 cycles of therapy, she experienced progression
• Her CBC, liver, and kidney function at the time of progression were within normal limits
• Her oncologist initiated therapy with eribulin mesylate (1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle)
• She experienced a partial response. Dose was reduced to 1.1 mg/m2 after she developed grade 3 peripheral neuropathy
• Her condition improved at the reduced dose and she continues in remission after 4 cycles