Time-to-chemotherapy results of the PALOMA-2 and -3 trials in HR+/HER2- metastatic breast cancer, which combined frontline palbociclib and endocrine therapy.
Massimo Cristofanilli, MD, FACS: One of the secondary end points for most of the CDK4/6 phase 3 registration studies has been to analyze quality of life and delay in the use of chemotherapy. One of the first analyses reported with regard to the PALOMA-3 study, which had a targeted population more at risk, showed a significant improvement in the delay of chemotherapy use in these patients, and subsequently did not show any…of the prior use of CDK4/6 inhibitors on the benefit of subsequent chemotherapy used at the time that the physician felt appropriate. You can imagine that anything between 18 and 24 months delay in chemotherapy use has a significant impact on the quality of life of these patients, irrespective of the chemotherapy, since we know that the majority of chemotherapy major adverse effects are quite different from the toxicity profile of a CDK4/6 inhibitor.
This has been shown as an…analysis of the phase 3 PALOMA-2 and PALOMA-3, which were consistent in these 2 studies, and other studies as well later. The delay in chemotherapy was an important end point, shown later also in the MONALEESA-3 study. Essentially, as I mentioned, this is one of the secondary end points of this phase 3 registration study for CDK4/6. It’s important and significant for women who have been diagnosed with this disease that is now becoming treated more as a chronic condition, with overall survival of 25% to 40% at 5 years, indicating that this patient would remain on this treatment for a longer time. At some point, it will be necessary to introduce chemotherapy, but it will be much later in the natural history of their disease.
There are different conditions with regard to patients with metastatic disease. In these studies, we have looked very carefully, for example, at site of recurrence. Patients with visceral metastases, liver metastases, have the most aggressive type of metastatic disease, even in hormone receptor-positive disease, and use chemotherapy earlier compared to patients with bone-only disease. Irrespective of that, there is an improvement and a delay in chemotherapyalso in patients with visceral metastasis, and with liver metastasis, which is most aggressive and more difficult to treat. We will say across the board, irrespective of the type of recurrence and type of progression and the organ involvement, the combination with a CDK4/6, in this case with PALOMA-2 or PALOMA-3 with Ibrance [palbociclib], was able to delay the use of chemotherapy.
Transcript edited for clarity.