What Does the Future Hold for the Treatment of Metastatic Breast Cancer?

What treatments are on the horizon for metastatic breast cancer? To gain insight into this question, Medscape interviewed breast cancer expert Eric P. Winer, MD, director of Yale Cancer Center; physician-in-chief at Smilow Cancer Network; and chair of the Board of the American Society of Clinical Oncology. Read on for his insights.

What does the future hold for the treatment of metastatic breast cancer? What drugs are on the horizon in the next few years?

I think we are going to see some development in the antibody drug conjugate space, and there are a number of new agents that are being evaluated. There will be more that goes on in the whole area around targeted therapies, and especially targeted therapies focusing on the PI3 kinase pathway, where there are some new drugs that are looming. Then, given the success of the CDK4/6 inhibitors and interest in other CDK inhibitors, there are data with CDK2 inhibitors and other CDK inhibitors that I think will be of interest during the next few years. The bottom line for metastatic breast cancer is that I think we are going to see more effective therapies, more targeted therapies, and, I hope, therapies that are better tolerated by patients.

Can you name a few of the antibody drug conjugates that are in development?

The one that comes to mind immediately is Dato-DXd.

And can you name a few of the PI3 kinase drugs?

There is a new drug that there is a lot of buzz about from Genentech; I don't believe that drug has a name yet. It is still going by a number, to the best of my knowledge. There will be a presentation at the San Antonio Breast Cancer Symposium (SABCS) in the next day or two. [Editor's note: Please refer to the press release "Genentech's Kadcyla Is the First Targeted Therapy to Show Significant Overall Survival Benefit in People With HER2-Positive Early-Stage Breast Cancer With Residual Invasive Disease After Neoadjuvant Treatment" and coverage of " GS03-12: Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis," which was presented at SABCS.]

Can you talk about the new CDK4/6 inhibitors on the horizon?

We have three CDK4/6 inhibitors currently available, and there are a number of drugs that target a number of other CDKs. Some are really in the earliest stage of development and some are a little further along, but the bottom line is that I think we are going to see more drugs investigating ways of getting around CDK4/6 inhibitor resistance.

Can you elaborate on them?

Probably not, because I would be giving you confidential data. I don't think it is of interest to most Medscape readers to just see names of drugs. I think what is more interesting is to hear about general approaches. So, looking at what to do after progression after CDK4/6 inhibitors is interesting. The whole area of new antibody drug conjugates is really important, and I do think that given the relatively poor tolerability of the present PI3 kinase inhibitor, which is alpelisib, looking at new ways of inhibiting the PIK3CA gene is going to be important.

What are the main toxicities with alpelisib?

There can be a lot of gastrointestinal toxicity, skin toxicity, and pulmonary toxicity.

So, do you think the new agents will focus on achieving the same target but without the toxicities?

Exactly.

Do many patients go off of alpelisib because of the toxicities?

A fair number go off the drug because of toxicities, and there are many doctors who don't use that drug with any frequency because of the toxicities.

In terms of antibody drug conjugates, do you see that space getting really crowded?

I don't think it is nearly saturated. I think we are going to see more and more antibody drug conjugates. It appears to be a very effective way of delivering drugs, and people are really enthusiastic about it.

What does the future hold for treatments for metastatic breast cancer in the next 10 years?

There is still a great deal of interest in immunotherapy, particularly in triple-negative breast cancer, and how we can combine immunotherapy with other treatments to make it better.

I think the other thing that we are going to see is particularly for patients who present de novo with metastatic breast cancer, so that is their first metastatic breast cancer presentation (meaning they didn't get treated 2 or 3 or 8 years ago). I think we are going to see people begin to increasingly talk about the potential of curative therapy, particularly for HER2-positive and triple-negative breast cancer.

Can you elaborate on that?

In HER2-positive breast cancer, for example, we know that there is a small proportion of patients who present de novo with HER2-positive breast cancer who receive an initial regimen with chemotherapy, trastuzumab, and pertuzumab, and who have a great response and many years later have no evidence of cancer.

As we develop more effective drugs, I think you are going to see them combined in different ways, with the hope that we may see in some people that we're not just treating a chronic disease and treating it well for a long time, but that we're actually curing them.

What about new targeted agents that we haven't talked about? What about PARP inhibitors?

I'm not sure that we are in any terribly different place with the PARP inhibitors. I think there is still an interest in exploring the PARP inhibitors in various combinations, maybe even in patients who don't have the BRCA1 and BRCA2 mutations. There is certainly an interest in looking at using them in patients who have somatic mutations. But I'm not aware of new PARP inhibitors coming out. I could be wrong.

Are there other new targets that are just in the experimental stage? Are there new pathways that are on the horizon?

As I'm sure you know, there are drugs that are targeting estrogen receptor 1 mutations. As we understand the biology more and as we understand resistance more, and as we understand resistance in different settings — for example, resistance to some of the antibody drug conjugates — I think we may identify new targets. I don't have any specific ones to mention.

Is there anything else you would like to add?

We still have over 40,000 women die each year from breast cancer. The number of women who are living longer with metastatic breast cancer is going up. The number of women who could potentially be cured of this is very slowly, I think, going to go up in the years ahead. Treatments are getting better, but we still have a lot of work to do.

Eric P. Winer, MD, has disclosed no relevant financial relationships.

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Image 1: Courtesy of Eric P. Winer, MD

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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: What Does the Future Hold for the Treatment of Metastatic Breast Cancer? - Medscape - Dec 22, 2023.