Pfizer officially submits the application for new breast cancer drug palbociclib to Da

This time, Pfizer submitted the combination of palbociclib and letrozole The indications were estrogen receptor positive and HER2 negative advanced breast cancer The application is based on the company's phase II clinical study Palbociclib is a new type of oral cdks-4 and cdks-6 inhibitors, which can prevent the spread of cancer cells by controlling cell cycle The drug was awarded the "breakthrough therapy" certification by FDA in April 2013 The drug has entered two clinical phase III trials Pfizer Seeks FDA Approval for Palbociclib   Pfizer has submitted a New Drug Application for palbociclib plus letrozole as a fro ntline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer, ba sed on findings from the phase II PALOMA-1 trial The FDA will review the application within 60 days, at which point the agency will establish a review timeline for the novel CDK 4/6 inhibitor under the Pres cription Drug User Fee Act The fastest review under this program provides a decision within 6 months “Today’s submission marks an im portant milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer,” Garry Nicholson, president of Pfizer Oncology, said in a press release Inhibition of CDK 4/6 prevents DNA replication by prohibiting progression from G1 to S phase during cell division Blocking this mechanism prevents tumor cell proliferation through co ntrol of the cell cycle The ratio nale for the combination of an aromatase inhibitor with palbociclib stemmed from early preclinical evidence suggesting that CDK 4/6 is more active in patients with ER-positive breast cancer, as a result of an intact retinoblastoma (Rb)-pathway Palbociclib initially generated excitement at the 2012 San Anto nio Breast Cancer Symposium when interim results from the PALOMA-1 trial demo nstrated a dramatic improvement in progression-free survival (PFS) for the combination of palbociclib and letrozole versus letrozole alone ba sed on these findings, the FDA granted palbociclib a breakthrough therapy designation in April 2013 In the open-label PALOMA-1 study, 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer were randomized in a 1:1 ratio in two parts: Part 1 co ntained 66 patients and Part 2 had 99 patients Co ntinuous 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 primary endpoint was PFS by investigator assessment According to an updat presented at the 2014 AACR Annual Meeting in April 2014, the median PFS was 20.2 mo nths with palbociclib compared with 10.2 mo nths for letrozole alone (HR = 0.488; P = .0004) The median overall survival (OS) was 37.5 mo nths with palbociclib compared with 33.3 mo nths with letrozole alone (HR = 0.813; 95% CI, 0.492-1.345; P = .2105) However, this first analysis of OS co ntained data from o nly 61 patients (37%) and was not deemed statistically significant The most commo nly reported treatment-related adverse events in the combination arm were neutropenia, leukopenia, anemia, and fatigue Neutropenia in the study was not cumulative and febrile neutropenia was not reported According to analysis presented at the 2014 ASCO Annual Meeting, palbociclib-induced neutropenia is generally short lasting and reversible with co nservative management This study combined safety data from 140 patients across two phase II studies of single-agent palbociclib in patients with various Rb-positive tumors Overall, grade 3/4 neutropenia was present in 39% of patients Grade 3 anemia occurred in 4% of patients and grade 3 thrombocytopenia was apparent in 9% A number of Pfizer-spo nsored phase III clinical trials are exploring palbociclib as a treatment for patients with advanced breast cancer Given the benefit demo nstrated in the PALOMA-1 trial, these studies will be randomized in a 2:1 ratio favoring treatment with palbociclib The PALOMA-2 trial is comparing the combination of palbociclib and letrozole with letrozole alone as a fro ntline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer (NCT01740427) The PALOMA-3 trial is comparing palbociclib plus fulvestrant against fulvestrant alone in women with HR-positive, HER2-negative me tastatic breast cancer following progression on prior endocrine therapy (NCT01942135) In addition to Pfizer spo nsored studies, a number of investigator-led phase III trials have been established to explore palbociclib across a number of settings These studies randomize patients in a 1:1 ratio to palbociclib in combination with hormo nal therapy or chemotherapy The open-label phase III PEARL trial will compare exemestane plus palbociclib with capecitabine in HR-positive patients with me tastatic breast cancer who are resistant to treatment with non-steroidal aromatase inhibitors (NCT02028507) The phase III PENELOPE-B trial will examine post-neoadjuvant treatment with palbociclib plus endocrine therapy in HR-positive patients with residual disease following chemotherapy and surgery (NCT01864746)