Joyce O’Shaughnessy, MD: We heard an oral presentation here at AACR [American Association for Cancer Research] from Dr. Matthew Goetz regarding MONARCH 3 regarding final progression-free survival [PFS] data. MONARCH 3 is the first-line trial of a nonsteroidal AI [aromatase inhibitor] with or without abemaciclib in first-line metastatic breast cancer that is ER [estrogen receptor]-positive, HER2 [human epidermal growth factor receptor 2]-negative. In the preplanned final PFS results, median PFS of the abemaciclib arm was 28 months versus 14 months. It’s interesting. Across all 3 of the first-line CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitor trials, the median PFS on the control arm is coming in right around 14 months. It’s very, very interesting how similar they are. And 28 months is actually the highest median PFS we’ve seen in the preplanned analysis. The final analysis for PFS was a hazard ratio of 0.54, highly statistically significant. These are very encouraging results. The overall survival data are immature.
The other point that caught my interest on this final analysis of PFS from MONARCH 3 is that by cycle 2, the median reduction in tumor volume was 30%. That’s very important because it means that the effectiveness of abemaciclib—this was on the abemaciclib arm—is very rapid, and that’s important. It’s a powerful antiproliferative drug, so we would expect a rapid result as we would from chemotherapy. But it’s very important to see it, because for patients who come in with either some abnormal liver function tests, symptoms, or abnormal lung function, etc, we need rapid reduction in tumor volume to help symptomatically. So that was very, very good to see.
Interestingly as well, though the responses were fast, patients continued to respond. If you look at reduction in tumor volume, it wasn’t just in the first few months and then stable. It continued to go down through month 24. So, it was very continuous, suggesting to me that hypothetically we may be seeing some immune effects. When you see that continued benefit over a long period of time, it usually means there is some immune stimulation and some therapeutic benefit from an immune response. There is no difference in toxicities that we’re aware of from the abemaciclib regarding diarrhea, some fatigue, very modest neutropenia, and about 3% of patients who did have deep vein thrombosis, a thrombotic event, with the abemaciclib. There’s nothing new there. But the PFS data held up and even looked a little bit better at the final PFS analysis.
Here at the AACR [American Association for Cancer Research] annual meeting, we also had an update on the MONARCH 1 data, which led to the approval of abemaciclib as a single agent in pretreated patients in the metastatic setting. In MONARCH 1, the dose of abemaciclib was 200 mg BID [twice a day] continuously. Patients had to have had at least 2 prior endocrine therapies in the metastatic setting and were required to have had 1 prior chemotherapy regimen, but no more than 2, in the metastatic setting. The final analysis showed the response rate had not changed: It was 19.7%. The clinical benefit rate had not changed and is 42%. The overall survival is now mature and final at 22 months median survival. It’s not a randomized trial, so you really can’t say too much about that. It’s certainly a reasonable survival result in this pretreated population. It again reinforces the fact that as a single agent in pretreated patients, abemaciclib is quite a non—cross-resistant agent in this population.
Abemaciclib is also now in the MONARCH E trial, E standing for early breast cancer, as adjuvant therapy. Patients can receive either neoadjuvant or adjuvant chemotherapy, then they’re randomized to placebo for 2 years or to abemaciclib for 2 years at 150 mg BID continuously along with endocrine therapy, whether that be an aromatase inhibitor, tamoxifen, or an LHRH [luteinizing hormone-releasing hormone] agonist added in. Now, the MONARCH E trial is being conducted in women with high-risk early breast cancer, and that’s defined as 4 or more positive nodes. If a woman has 1 to 3 positive nodes, she has to have T3 or greater disease, grade 3 disease. Starting this summer, there will be a cohort opening for 1 to 3 positive nodes with a high Ki-67, 20% or more, really aiming at a population that is at risk for developing metastasis early on. These are patients who we really don’t have the answers for; we need more tools for these patients. It’s a global trial. It’s accruing very well, so hopefully that will be a step forward for patients with the more aggressive, heavily tumor-burdened, early breast cancer.
Transcript Edited for Clarity