Ibrance trial stopped early on survival benefit

A phase 3 trial of Pfizer’s breast cancer therapy Ibrance has been stopped early after a clear benefit on progression-free survival was seen compared to control.

The PALOMA-3 study of recently-approved Ibrance (palbociclib) showed that giving the drug in combination with AstraZeneca’s Faslodex (fulvestrant) to women with oestrogen receptor positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer was more effective than fulvestrant alone.

The FDA approved Ibrance – the first cyclin-dependent kinase (CDK) 4 and 6 inhibitor to reach the market – for use in HR+/HER2- breast cancer in combination with letrozole in February. This was based on results from the PALOMA-1 trial, which showed that adding Ibrance to letrozole almost doubled PFS to more than 20 months.

Both fulvestrant and letrozole are aromatase inhibitors and have been widely used as first-line therapies for ER+ breast cancer for many years, although many patients go on to develop resistance to the class. The new data how indicate that Ibrance provides additional benefit in two leading treatments in the class.

Ibrance was granted accelerated approval by the FDA on the strength of its superiority of the combination over letrozole alone, with conditional approval on the understanding that a follow-up study – PALOMA-2 – backs up the earlier findings.

Mace Rothenberg, chief medical officer for Pfizer oncology, said the company would now discuss the PALOMA-3 data with health authorities “regarding a regulatory path forward.”

Analysts have predicted that the drug could eventually achieve sales of up to $5 billion a year, with some suggesting it could climb even further, perhaps reaching as high as $10 billion.

Around 60 per cent of breast cancer patients in the US have the ER+/HER2- receptor profile. Moreover, while women with HER2+ breast cancer have a number of therapeutic options, the far greater population with HER2- tumours have seen fewer new drug developments in recent years, adding to the importance of Ibrance as a therapeutic option.

Novartis’ mTOR inhibitor Afinitor (everolimus) was approved as a welcome addition to the ER+/HER2- armamentarium in 2012, but there have been a series of trial failures in this setting since then, including candidates such as Bayer’s Nexavar (sorafenib), Eli Lilly’s ramucirumab and most recently Nektar’s NKTR-102 (etirinotecan pegol).

Along with Ibrance, oncologists are also hoping for positive news in HER2- breast cancer from the new checkpoint inhibitors – Merck’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab) – as well as AbbVie’s PARP inhibitor veliparib and Roche’s established cancer drug Avastin (bevacizumab).

Meanwhile, other companies vying to develop CDK inhibitors include Lilly, which has bemaciclib (formerly LY2835219) in late-stage development, as well as Novartis, whose LEE011 candidate which began phase 3 trials at the end of 2013.

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