Pfizer has posted mixed results for its palbociclib, leaving hope for trailing competitors like Novartis and Lilly.

The lowdown: Cyclin-dependent kinases (CDKs), which drive the cell cycle and therefore cell proliferation, have been a focus for drug developers since the 1990s (Nature Rev. Drug Discov. 11, 892–894; 2012). With recent mixed results from Pfizer and Amgen's first-in-class CDK4 and CDK6 inhibitor palbociclib, however, they could at last be approaching the market.

Pfizer and Amgen reported results from an open-label 165-patient Phase I/II trial of palbociclib in postmenopausal women with oestrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2−) advanced metastatic breast cancer at the American Association for Cancer Research (AACR) annual meeting. The drug in combination with the aromatase inhibitor letrozole hit its primary end point, inducing a progression-free survival (PFS) of 20.2 months versus 10.2 months in controls. But, this improvement was down from interim analysis PFS estimates. The trial also failed on its secondary end point of overall survival: there was no statistical difference between the 37.5-month overall survival on treatment compared with the 33.3 months on control.

On the basis of these results Pfizer is reportedly considering filing for approval of palbociclib, which has breakthrough therapy designation from the US Food and Drug Administration. Two pivotal trials of the drug in combination with letrozole and with selective ER downregulator fulvestrant are also ongoing. According to Thomson Reuters Cortellis, the consensus annual sales forecasts from five analysts for the drug currently sit at US$1.9 billion by 2019.

A pipeline of other CDK inhibitors is also in the clinic for a range of oncology indications. Novartis initiated a Phase III trial of its CDK4 and CDK6 inhibitor LEE011 in breast cancer in January. Lilly's CDK4 and CDK6 inhibitor bemaciclib (LY2835219) is in a Phase II trial for mantle cell lymphoma, and the company also presented promising results for the drug in breast cancer at the AACR. Merck & Co.'s dinaciclib, a CDK2, CDK2, CDK5 and CDK9 inhibitor, is in Phase II trials for acute lymphoblastic leukaemia, acute myeloid leukaemia, breast cancer, melanoma and non-small-cell lung carcinoma.