New CDK4/6i Data Move Metastatic Breast Cancer Field Forward

Kevin Kalinsky, MD


June 27, 2017

Hello. I'm Kevin Kalinsky, here at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO). I'm a breast oncologist at Columbia University in New York City. I will be talking with you a little bit about the important metastatic breast cancer session.


The first important breast cancer session was the metastatic oral abstract session. In particular, the first half of the session was really about CDK4/6 inhibitors. In the first oral presentation, George Sledge, MD, presented data on MONARCH-2.[1] These are the first randomized data that we are seeing with abemaciclib. Last year at ASCO, we saw [results of] single-agent activity in a more heavily pretreated population in MONARCH-1.[2]

Patients in MONARCH-2 received fulvestrant as a backbone, plus or minus abemaciclib. One thing to note: All of these patients previously had progressed on aromatase inhibitor therapy in the adjuvant or neoadjuvant setting within a year, or they had progressed in the metastatic setting and went on to get fulvestrant. Nobody had chemotherapy. Ultimately, this was a very different population from that of PALOMA-3,[3] and as a result, the control arm for MONARCH-2 was longer than for PALOMA-3.

This study demonstrated that there was very significant improvement in progression-free survival, with the hazard ratio very similar to what we see with other CDK4/6 inhibitors, including the PALOMA-2[4] and MONALEESA-2[5] studies with palbociclib and ribociclib, respectively. It demonstrates that this is a good class effect with these agents.

The side-effect profile with abemaciclib is different from what we see with the other CDK4/6 inhibitors. There is less neutropenia but more diarrhea. The dose of abemaciclib had to be amended and was reduced from 200 mg to 150 mg. We are excited about these data.


Another interesting presentation during that session included the updated analysis of overall survival data for PALOMA-1,[6] the randomized phase 2 trial that led to the accelerated approval of palbociclib. It is really important to reiterate that this study was not powered to look for overall survival. It was a small study. They did see a trend for an improvement in overall survival but it was not statistically significant. The take-home [message] should be that there was not a statistical improvement in overall survival but there was an interesting trend.


The third presentation in that session was about patients who had never received a CDK4/6 inhibitor. These more heavily pretreated patients in the TREnd study[7] were randomized to get palbociclib or palbociclib plus endocrine therapy (ie, the endocrine therapy that they had just received). There was a benefit for them to get a CDK4/6 inhibitor in that arena.

Important Questions Remain

This was another ASCO session where we could see that CDK4/6 inhibitors have moved the field forward for hormone receptor–positive and HER2-negative metastatic breast cancer. These drugs are now being evaluated in various studies in the operable setting. What the utility of those drugs will be in that setting remains an important question. Other important questions include sequencing [these agents], and if a patient progresses on a CDK4/6 inhibitor plus hormone therapy, [determining] whether we should switch the hormone therapy and continue a CDK4/6 inhibitor. There are studies that are looking at that question.

Also, right now in the field, we do not have any biomarkers to predict response or resistance. Biomarkers are important to help us differentiate [between agents] and ultimately predict who may respond to one [agent] versus another.

At the end of the day, this was an important session. CDK4/6 inhibitors have really been a game-changer for this disease. Thank you.


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