The next few weeks will see quite a lot of activity here on Biotech Strategy Blog with the segue from Miami Breast Cancer Conference to the World Lung Conference in Geneva and then onto the annual AACR meeting in San Diego.
Over the last year, we’ve seen a lot of attention focused on immuno-oncology, but very little of the data has emerged yet in breast cancer. Instead, we’ve seen a new approval for pertuzumab (Perjeta) in neoadjuvant disease, based on pCR. You can read more about new developments in targeting HER2 in neoadjuvant breast cancer in the last post.
One area that has generated a lot of interest in metastatic breast cancer is CDK inhibition, whether that be the potential for targeting 1 and 2 in triple negative disease, or targeting 4 and 6, in ER positive situations, for example. Some inhibitors are more specific (Pfizer’s palbociclib and Novartis’s LEE011 target CDK4/6), whereas others hit a broader spectrum such as Merck’s dinaciclib, which inhibits CDK1/2/5/9. The challenge with pan inhibitors is that if the target is doesn’t matter to the tumour then there is potential for unwanted off-target side effects.
Last month Pfizer announced that the topline phase II results from the PALOMA –1 trial with their CDK4/6 inhibitor, palbociclib, were positive – no doubt we will see an ODAC meeting soon to discuss the FDA application and possible accelerated approval. The company received Breakthrough Therapy Designation in April last year and given the survival curves from the phase II study that have previously been presented at SABCS, I think they make a very good case for early approval.
Recall that the interim analysis demonstrated very compelling median progression free survival (PFS) of 26.1 months for palbociclib when combined with letrozole compared to only 7.5 months with letrozole alone in women who were post-menopausal with newly diagnosed ER+ HER2- breast cancer. obviously the final results will be important in influencing any FDA decision, but by whatever yardstick you use, those were very impressive data indeed.
The phase III trials, PALOMA–2 and PALOMA–3, are already open and enrolling patients.
Other companies also have CDK4/6 inhibitors in clinical development, including Lilly and Novartis.
Today’s post focuses on progress in targeting CDK4/6, including highlights from an interview with William Sellers MD, PhD from the Novartis Institute of Biomedical Research (NIBR).