PATINA Trial Shifts Paradigm in HER2+/ER+ Breast Cancer Treatment, Prolonging Survival With Targeted Combination Therapy

This is a transcript of a video essay, which can be found on Medscape.

I’m here with you today to talk about what I think was one of the most important trials reported at the December San Antonio Breast Cancer Symposium meeting, the PATINA trial.

This is a trial that was not on our radar as we were looking forward to the meeting. In fact, it wasn’t on the agenda because the results didn’t become available until about a week and a half before the meeting kicked off. Kudos to the authors for getting these data out there, and to the organizers for recognizing the importance and finding a way to add this to the program. 

The PATINA trial enrolled patients whose tumors were both HER2 positive and ER positive. That is about half of our patients with HER2-positive disease. 

Almost all of our trials looking at HER2-targeted therapies did not allow patients to continue antiestrogen therapy. Patients could have had antiestrogen therapy before they came to those HER2-focused trials. Some did, some may not have. It was not a requirement, but they could not continue it. 

The same is true for patients with ER-positive disease. If your disease was ER positive and HER2 positive, you were excluded from all of our recent trials focusing on ER-positive disease. That includes those looking at the benefit of cyclin-dependent kinase inhibitors. 

It also includes those looking at PI3 kinase inhibitors, AKT inhibitors, and selective estrogen receptor downregulators in their oral formulations. We›ve had to pick: Do we want to focus on HER2 or do we want to focus on ER? The PATINA trial results are not only important for practice, but they also show us the problem in that dichotomy.

PATINA enrolled patients who were receiving their first chemotherapy and HER2-targeted therapy for metastatic disease. Once they had received at least four cycles of combined therapy, they could receive additional chemotherapy, but they could also move into a maintenance phase if their disease was responding or stable, continuing HER2-targeted therapy alone without chemotherapy.

At that point, hormone therapy was reintroduced. This is a common practice for many of us. Those patients were then randomized to either palbociclib or not. This was a large effort, with 518 patients in this randomized trial. The expectations of progression-free survival were based on the results of the CLEOPATRA trial.

The trial assumed about a 15-month progression-free survival in those randomized to the control arm. What was actually observed was a 29-month progression-free survival. Two things might have contributed to this difference. 

First, the CLEOPATRA trial did not allow patients to receive concurrent hormone therapy, and that may have had a major impact on its own. Also, CLEOPATRA reported the PFS for all of the patients enrolled. To get into PATINA, you had to be responding or stable to your initial combined modality therapy. Those patients with really resistant disease who progressed early were excluded, and that may have had an impact as well. 

With the addition of palbociclib, that 29-month progression-free survival became 44 months. Stop and think about this. There was almost a 4-year period of time where patients were on trastuzumab and pertuzumab, an aromatase inhibitor, and a cyclin-dependent kinase inhibitor. No chemotherapy, much less day-to-day toxicities — not no toxicity, but less of the day-to-day toxicities that patients are really troubled by. 

We don’t yet have mature overall survival data. Those will be coming. You can imagine with progression-free survival nearing 4 years, overall survival data will be some months or years hence until there are enough events for us to look at that evaluation. 

Realizing that there are going to be issues with insurance approval and regulatory approvals, I would like to take these results into account for my patients in that situation.

It also challenges those of us who are developing clinical trials and drugs to realize that studying targets in isolation is needed early in the development of new agents. To get the maximum benefit for our patients, you need to put those building blocks back together and stop this forced dichotomy.

That doesn’t serve our patients well and it’s not where we will need to be in the future.

Kathy D. Miller, Professor of Medicine, Indiana University School of Medicine; Co-Director, Breast Cancer Program, Indiana University Simon Cancer Center, Indianapolis, Indiana, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This is a transcript of a video essay, which can be found on Medscape.

I’m here with you today to talk about what I think was one of the most important trials reported at the December San Antonio Breast Cancer Symposium meeting, the PATINA trial.

This is a trial that was not on our radar as we were looking forward to the meeting. In fact, it wasn’t on the agenda because the results didn’t become available until about a week and a half before the meeting kicked off. Kudos to the authors for getting these data out there, and to the organizers for recognizing the importance and finding a way to add this to the program. 

The PATINA trial enrolled patients whose tumors were both HER2 positive and ER positive. That is about half of our patients with HER2-positive disease. 

Almost all of our trials looking at HER2-targeted therapies did not allow patients to continue antiestrogen therapy. Patients could have had antiestrogen therapy before they came to those HER2-focused trials. Some did, some may not have. It was not a requirement, but they could not continue it. 

The same is true for patients with ER-positive disease. If your disease was ER positive and HER2 positive, you were excluded from all of our recent trials focusing on ER-positive disease. That includes those looking at the benefit of cyclin-dependent kinase inhibitors. 

It also includes those looking at PI3 kinase inhibitors, AKT inhibitors, and selective estrogen receptor downregulators in their oral formulations. We›ve had to pick: Do we want to focus on HER2 or do we want to focus on ER? The PATINA trial results are not only important for practice, but they also show us the problem in that dichotomy.

PATINA enrolled patients who were receiving their first chemotherapy and HER2-targeted therapy for metastatic disease. Once they had received at least four cycles of combined therapy, they could receive additional chemotherapy, but they could also move into a maintenance phase if their disease was responding or stable, continuing HER2-targeted therapy alone without chemotherapy.

At that point, hormone therapy was reintroduced. This is a common practice for many of us. Those patients were then randomized to either palbociclib or not. This was a large effort, with 518 patients in this randomized trial. The expectations of progression-free survival were based on the results of the CLEOPATRA trial.

The trial assumed about a 15-month progression-free survival in those randomized to the control arm. What was actually observed was a 29-month progression-free survival. Two things might have contributed to this difference. 

First, the CLEOPATRA trial did not allow patients to receive concurrent hormone therapy, and that may have had a major impact on its own. Also, CLEOPATRA reported the PFS for all of the patients enrolled. To get into PATINA, you had to be responding or stable to your initial combined modality therapy. Those patients with really resistant disease who progressed early were excluded, and that may have had an impact as well. 

With the addition of palbociclib, that 29-month progression-free survival became 44 months. Stop and think about this. There was almost a 4-year period of time where patients were on trastuzumab and pertuzumab, an aromatase inhibitor, and a cyclin-dependent kinase inhibitor. No chemotherapy, much less day-to-day toxicities — not no toxicity, but less of the day-to-day toxicities that patients are really troubled by. 

We don’t yet have mature overall survival data. Those will be coming. You can imagine with progression-free survival nearing 4 years, overall survival data will be some months or years hence until there are enough events for us to look at that evaluation. 

Realizing that there are going to be issues with insurance approval and regulatory approvals, I would like to take these results into account for my patients in that situation.

It also challenges those of us who are developing clinical trials and drugs to realize that studying targets in isolation is needed early in the development of new agents. To get the maximum benefit for our patients, you need to put those building blocks back together and stop this forced dichotomy.

That doesn’t serve our patients well and it’s not where we will need to be in the future.

Kathy D. Miller, Professor of Medicine, Indiana University School of Medicine; Co-Director, Breast Cancer Program, Indiana University Simon Cancer Center, Indianapolis, Indiana, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This is a transcript of a video essay, which can be found on Medscape.

I’m here with you today to talk about what I think was one of the most important trials reported at the December San Antonio Breast Cancer Symposium meeting, the PATINA trial.

This is a trial that was not on our radar as we were looking forward to the meeting. In fact, it wasn’t on the agenda because the results didn’t become available until about a week and a half before the meeting kicked off. Kudos to the authors for getting these data out there, and to the organizers for recognizing the importance and finding a way to add this to the program. 

The PATINA trial enrolled patients whose tumors were both HER2 positive and ER positive. That is about half of our patients with HER2-positive disease. 

Almost all of our trials looking at HER2-targeted therapies did not allow patients to continue antiestrogen therapy. Patients could have had antiestrogen therapy before they came to those HER2-focused trials. Some did, some may not have. It was not a requirement, but they could not continue it. 

The same is true for patients with ER-positive disease. If your disease was ER positive and HER2 positive, you were excluded from all of our recent trials focusing on ER-positive disease. That includes those looking at the benefit of cyclin-dependent kinase inhibitors. 

It also includes those looking at PI3 kinase inhibitors, AKT inhibitors, and selective estrogen receptor downregulators in their oral formulations. We›ve had to pick: Do we want to focus on HER2 or do we want to focus on ER? The PATINA trial results are not only important for practice, but they also show us the problem in that dichotomy.

PATINA enrolled patients who were receiving their first chemotherapy and HER2-targeted therapy for metastatic disease. Once they had received at least four cycles of combined therapy, they could receive additional chemotherapy, but they could also move into a maintenance phase if their disease was responding or stable, continuing HER2-targeted therapy alone without chemotherapy.

At that point, hormone therapy was reintroduced. This is a common practice for many of us. Those patients were then randomized to either palbociclib or not. This was a large effort, with 518 patients in this randomized trial. The expectations of progression-free survival were based on the results of the CLEOPATRA trial.

The trial assumed about a 15-month progression-free survival in those randomized to the control arm. What was actually observed was a 29-month progression-free survival. Two things might have contributed to this difference. 

First, the CLEOPATRA trial did not allow patients to receive concurrent hormone therapy, and that may have had a major impact on its own. Also, CLEOPATRA reported the PFS for all of the patients enrolled. To get into PATINA, you had to be responding or stable to your initial combined modality therapy. Those patients with really resistant disease who progressed early were excluded, and that may have had an impact as well. 

With the addition of palbociclib, that 29-month progression-free survival became 44 months. Stop and think about this. There was almost a 4-year period of time where patients were on trastuzumab and pertuzumab, an aromatase inhibitor, and a cyclin-dependent kinase inhibitor. No chemotherapy, much less day-to-day toxicities — not no toxicity, but less of the day-to-day toxicities that patients are really troubled by. 

We don’t yet have mature overall survival data. Those will be coming. You can imagine with progression-free survival nearing 4 years, overall survival data will be some months or years hence until there are enough events for us to look at that evaluation. 

Realizing that there are going to be issues with insurance approval and regulatory approvals, I would like to take these results into account for my patients in that situation.

It also challenges those of us who are developing clinical trials and drugs to realize that studying targets in isolation is needed early in the development of new agents. To get the maximum benefit for our patients, you need to put those building blocks back together and stop this forced dichotomy.

That doesn’t serve our patients well and it’s not where we will need to be in the future.

Kathy D. Miller, Professor of Medicine, Indiana University School of Medicine; Co-Director, Breast Cancer Program, Indiana University Simon Cancer Center, Indianapolis, Indiana, has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.