Palbociclib (Ibrance)

Palbociclib approved for the treatment of women with metastatic breast cancer.

Trade name Ibrance.

Inhibits cyclin-dependent kinases (CKDs) 4 and 6, which are involved in promoting the growth of cancer cells.

Prevents downstream phosphorylation of the retinoblastoma protein

The drug is intended for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who have not yet received an endocrine-based therapy.

It is intended for use in combination with letrozole or fulvestrant.

Evaluated in a Phase II clinical trial of 165 postmenopausal women with ER-positive, HER2-negative metastatic breast cancer who had not received previous treatment for advanced disease: Patients received Ibrance in combination with letrozole or letrozole alone. Those receiving the Ibrance combination lived 20.2 months without disease progression, while patients receiving letrozole alone lived 10.2 months without disease progressing.

PALOMA-1/TRIO-18 trial of adding palbociclib to endocrine therapy in the first line treatment of patients with HER-2 negative luminal breast cancer resulted in the median progression free survival of 10.2 months in patients given letrozole compared to 20.2 months for patients given palbociclib plus letrozole.

PALOMA-3 study showed that when used as a second line treatment the combination of palboclib and everolimus nearly triples the time to progression.

The combination of letrozole and Palbociclib doubled the median progression-free survival.

The most common side effects are: neutropenia, leukopenia, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.

Monitoring of complete blood counts is required.

It is recommended that treatment begin with a 125 milligram dose for 21 days, followed by seven days without treatment.

It is advised to monitor complete blood count prior to start of therapy and at the beginning of each cycle, as well as on Day 14 of the first two cycles, and as clinically indicated.

PALOMA-3 A randomized study of palbociclib plus fulvestrant compared to fulvestrant alone revealing a progressive free survival in patients with advanced breast cancer ER positive with a median progressive survival of 9.2 months in women assigned combination and 3.8 months for women receiving fulvestrant alone.

In the above study both pre-and postmenopausal women derive benefit from the combination therapy.

125mg once daily for 21 days followed by 7 days off every 28 days.

Palbociclib (Ibrance) approved as a first-line treatment for patients with ER-positive metastatic breast cancer.

Phase II PALOMA-1 trial showed that the novel CDK 4/6-inhibitor in combination with letrozole reduced the risk of disease progression by 51% compared with letrozole alone.

Palbociclib (Ibrance) is a first-line treatment for patients with ER-positive metastatic breast cancer.

In the phase II PALOMA-1 trial, the CDK 4/6-inhibitor in combination with letrozole reduced the risk of disease progression by 51% compared with letrozole alone.

The median progression-free survival (PFS) with palbociclib was 20.2 versus with 10.2 months for letrozole alone.

The PALOMA-1 trial randomized 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer in a 1:1 ratio in two parts: Continuous daily letrozole was administered at 2.5 mg with or without palbociclib at 125 mg daily for 3 weeks followed by 1 week of rest until progression.

In Part 1 of the study, the median PFS was 26.7 months with palbociclib versus 5.7 months for letrozole alone.

In the larger Part 2, the median PFS was 18.1 versus 11.1 months, for palbociclib combination and letrozole, respectively.

The combination resulted in a response rate of 45% compared with 31% for the monotherapy and the overall clinical benefit rate was 70% versus 44%.

In the PALOMA-1trial the rate of grade 3/4 neutropenia was significantly higher in the palbociclib arm compared with letrozole alone (54% vs 1%) but no cases of febrile neutropenia or neutropenia-related infections were reported.

13% of patients discontinued treatment as a result of side effects in the palbociclib arm compared with 2% for letrozole.

The median progression-free survival (PFS) with palbociclib was 20.2 versus with 10.2 months for letrozole alone in postmenopausal patients with ER-positive, HER2-negative advanced breast cancer.

In the above trial continuous daily letrozole was administered at 2.5 mg with or without palbociclib at 125 mg daily for 3 weeks followed by 1 week of rest until progression.

The median overall survival (OS) was 37.5 months with palbociclib compared with 33.3 months with letrozole alone.

The combination resulted in a response rate of 45% compared with 31% for the monotherapy and the overall clinical benefit rate was 70% versus 44%.

Toxicity-wise the rate of grade 3/4 neutropenia was significantly higher in the palbociclib arm compared with letrozole alone (54% vs 1%).

Non-complicated grades of 3–4 neutropenia is the most common adverse event, and greater numbers of venous thromboembolism and cases of interstitial lung disease pneumonitis have been reported.

13% of patients discontinued treatment as a result of side effects in the palbociclib arm compared with 2% for

The PALOMA-2 trial is comparing the combination of palbociclib and letrozole with letrozole alone as a frontline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer.

The PALOMA-3 trial is comparing palbociclib plus fulvestrant against fulvestrant alone in women with HR-positive, HER2-negative metastatic breast cancer following progression on prior endocrine therapy.