Could CDK4/6 inhibitors be established in early-stage HR+ breast cancer?

Exciting developments continue to arise across many tumor types, with established medications looking for licensing in new and earlier indications. In HR+ HER2- breast cancer (BC), there is an opportunity for CDK4/6 inhibitors to enter the early-stage setting, with potential clear benefits for patients.

Pfizer’s blockbuster Ibrance leads in metastatic HR+ BC

With its initial approval in 2015, Pfizer’s Ibrance (palbociclib) has benefited from first-mover advantage in metastatic HR+ HER2- BC, enabling it to capture the lion’s share of the global market. In 2019 alone, Ibrance generated approximately $5bn USD in worldwide sales. In comparison, Novartis’ Kisqali (ribociclib) and Lilly’s Verzenio (abemaciclib) have faced greater challenges, trailing behind Ibrance as the second and third, respectively, to launch in this metastatic setting.

It is promising to see how Pfizer, Novartis and Lilly all continue to develop their brands in the space, while protecting or strengthening their market share. These are some of the behemoths of the industry about to play out in a competitive arena.

And there are benefits for patients in having brands such as Ibrance, with a wealth of real-world experience delivering positive outcomes.

So where are CDK4/6 inhibitors headed to next? And what might be the potential for these drugs in early HR+ HER2- BC?

The commercial opportunity across the CDK4/6 inhibitor class continues to grow

A wealth of data shows Ibrance and the subsequent CDK4/6 inhibitors have strong efficacy balanced with an acceptable safety profile in metastatic HR+ HER2- BC. If translated into early-stage settings, patients could benefit from novel treatment regimens involving a CDK4/6 inhibitor that may offer superior clinical benefit over current therapies such as chemotherapy or adjuvant endocrine monotherapy. Importantly, the possibility to replace toxic chemotherapy could have potential practice-changing implications that may establish CDK4/6 inhibitors as a new standard of care.

Data from Lilly’s monarchE and Pfizer’s PENELOPE-B are awaited

One could be optimistic for the potential of CDK4/6 inhibitors in early HR+ HER2- BC. Lilly recently announced that its Ph3 monarchE trial has been positive at a pre-planned interim analysis, indicating that adding Verzenio to standard adjuvant endocrine therapy significantly reduced the risk of cancer recurrence or death in high-risk patients. The full monarchE results are planned for a medical meeting later this year and are necessary to understand the actual magnitude of Verzenio’s benefit in this setting. Nonetheless, Lilly plans to submit these data to global regulatory authorities by the end of 2020.

Although Pfizer’s similar trial – Ph3 PALLAS – was negative at an interim analysis, upcoming results from Pfizer’s Ph3 PENELOPE-B are still awaited and could demonstrate Ibrance’s benefit after neoadjuvant chemotherapy. Should this study be successful, Ibrance could offer advantages given the CDK4/6 inhibitor’s ease of use and prescriber brand loyalty. In contrast, some side effects associated with Lilly’s Verzenio, such as GI toxicities, might impact patient quality of life in the early-stage setting when a drug’s duration of treatment is longer.

Regardless, one thing is evident – CDK4/6 inhibitors could soon be established as a new standard of care in early HR+ HER2- BC. The possible paradigm shifts and huge potential benefits for these BC patients bring renewed hope.