The Personal Side of Palbociclib

June 17, 2015

Just when you think you've run out of treatment options for a patient, new drugs are approved and quickly available. In the past year, there have been dozens of new drugs for all types of solid and blood malignancies. One of the most recent was just approved this year for breast cancer.

Just when you think you've run out of treatment options for a patient, new drugs are approved and quickly available. In the past year, there have been dozens of new drugs for all types of solid and blood malignancies. One of the most recent was just approved this year for breast cancer.

Bobbi is a 54-year-old female who was diagnosed 10 years ago age at the age of 44 with infiltrating ductal carcinoma of her right breast. The lump was not palpable; it was her yearly mammogram that detected the mass. Pathology revealed the grade was intermediate, estrogen receptor-positive, progesterone receptor-positive, and HER2/neu-negative. In late 2005, she underwent a lumpectomy to remove the 2.3 cm mass and of her 10 lymph nodes removed, there were two with macrometastasis.

She received adjuvant chemotherapy in the form of doxorubicin and cyclophosphamide followed by paclitaxel (4 cycles total). Then she followed with tamoxifen in a short course for maintenance, but needed a total hysterectomy and was switched to letrozole (Femara). She completed a total of 5 years of letrozole without any complications or progression in 2012. She suffers from right hip pain, but dismissed this as an old injury from a fall off a horse many years prior. Imaging in 2007 showed osteoporosis and it was treated with risedronate (Actonel).

Every year after her initial diagnosis, she received her screening mammograms which were benign. This year she had her most recent mammogram a month before her follow-up clinic visit with me, and it was also benign. At her regular oncology check-up, she shared that her right hip had been hurting more so lately, and even her right breast area.  

I examined the patient and she had point tenderness in her right flank area at the fifth and sixth rib area; same for her right hip area. We decided on a nuclear medicine whole body bone scan. The results were not good. There was bone metastasis in the same exact areas she was having pain, in addition to her sternum and skull areas. A bone biopsy of her right acetabulum confirmed breast cancer metastasis.

She started palliative radiation for pain control, received CT scans of her chest, abdomen, and pelvis, along with an MRI of the brain. Unfortunately, she now has lymph node involvement in the right pulmonary hila and mediastinal areas, and bilateral upper lobe nodules. The patient requested chemotherapy treatment again.

We shared with her that she had met the criteria for a new drug, palbociclib (Ibrance). This new drug received accelerated FDA-approval in February 2015 based on progression-free survival results. Palbociclib is now available for those with advanced hormone-positive, HER2/neu-negative breast cancer, like Bobbi.

Originally referred to as PD-0332991 in clinical trials, palbociclib is an oral, small-molecule inhibitor of cyclin-dependent kinases 4 and 6. The method of action inhibits the hormone activity by blocking Rb phosphorylation and is synergistic with aromatase inhibitors. The regimen involves continuous use of oral letrozole at a dose of 2.5 mg daily, plus oral palbociclib at a dose of 125 mg daily for 3 weeks, followed by 1 week off over 28-day cycles.

In the international PALOMA-1/TRIO-18 phase II study, one of the cohorts demonstrated median progression-free survival at 10.2 months for the letrozole only group and 20.2 months for the palbociclib plus letrozole group. Median overall survival was 33.3 months for the letrozole only group and 37.5 months in the palbociclib plus letrozole group.

Common side effects seen were limited to neutropenia (54%), leukopenia (19%), and fatigue (4%)-there were no cases of febrile neutropenia or neutropenia-related infections. Less common, but more serious side effects noted in the trial were pulmonary embolism (less than 4%), back pain (less than 2%), and diarrhea (less than 2%). No significant nausea or vomiting.

We are following Bobbi’s complete blood count each month, and if she experiences severe neutropenia or any other side effects, we can consider a dose reduction. So far we haven’t had to and she is tolerating the drug well in her first cycle. Stay tuned for further updates.

Is your cancer facility using this new drug? If so, what experiences can you share?

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