Outcomes4Me met with Dr. Steven Isakoff, a Breast Oncologist at Massachusetts General Hospital, to discuss the latest advancements in breast cancer amid the recent National Comprehensive Cancer Network (NCCN)® breast cancer treatment updates and scientific results published at recent conferences. Dr. Isakoff is the Associate Director of Clinical Research and the Director of the Triple Negative Breast Cancer Program at Massachusetts General Hospital. We have included the entire webinar video above for anyone who missed it and wants to watch it in full.
Here is a recap of the key takeaways from the discussion with Dr. Isakoff:
Dr. Isakoff, there’s been a number of recent updates and study results that impact breast cancer treatment and guidelines. Can you give an overview of the most recent changes and what they mean for patients?
Based on studies presented at the American Society of Clinical Oncology Meeting and the European Society of Medical Oncology Congress, there have been updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).
In one of these updates sacituzumab (Trodelvy) has now been moved to a “Preferred regimen”. This reflects recent data showing how highly active this drug is in triple negative breast cancer (TNBC). Data from the ASCENT trial shows an improvement in overall survival in TNBC where the median overall survival was more than doubled, from about 5 months to almost 11 months, in patients taking sacituzumab after at least two prior chemotherapy lines. The overall survival benefit helped move sacituzumab to be one of the preferred drugs available.
A second change is that atezolizumab (Tecentriq) has been removed from the guidelines. This followed Genentech/Roche’s decision to withdraw atezolizumab from marketing for TNBC under its FDA accelerated approval. Since there is another option in this space, pembrolizumab, the drug was removed from the guidelines to reflect Genentech/Roche’s decision.
Another interesting addition to the guidelines was the drug dostarlimab (Jemperli). Dostarlimab is added for patients who have a specific alteration called microsatellite instability or deficiency in mismatch repair genes. Although this is rare in breast cancer, if you have one of these molecular alterations, this drug was shown to be beneficial.
Another update is that the drug olaparib (Lynparza), which was included in the guidelines for advanced breast cancer with a BRCA1/2 mutation, is now added in early-stage breast cancer patients in specific situations with a BRCA1/2 mutation. This update is based on data from the Olympia study.
Also, very exciting, pembrolizumab (Keytruda) was added for early stage TNBC that is considered high-risk. The Keynote522 study showed that not only was there a significant improvement in the percent of patients with disappearance of their tumor, called a pathologic complete response, but this translated into a reduction in the risk of their cancer coming back after adding pembrolizumab to chemotherapy.
In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, testing criteria has been broadened to include any age patient if the result will guide treatment decisions, like to use PARP inhibitors. A theme that’s emerging in the genetic guidelines is that testing criteria is continuing to get broader.
I’m a 45-year-old breast cancer patient and have already been genetically tested. Should I get retested based on the new information?
It depends when you were most recently tested. If testing was done a number of years ago the answer may be yes. In general, now we do panel testing of multiple genes. We used to do just BRCA1/2 testing. If your testing was done before there was panel testing, it may be worthwhile to talk to your provider about getting updated testing.
I have early-stage breast cancer and was told 1 year ago that Olaparib is not approved for me. I am now hearing that it is, can you explain why that treatment option is now ok but was not over a year ago?
Olaparib is a PARP inhibitor. This drug was approved for advanced breast cancer patients with a BRCA1/2 mutation several years ago and we use it quite commonly. The Olympia study took patients with early-stage high-risk TNBC or ER+ high-risk breast cancer. After patients completed all chemotherapy, they were randomized to either receive no additional treatment if they had TNBC, or just anti-estrogen therapy if ER+, or olaparib was added for one year. At 3 years, 86% of patients who received olaparib did not have recurrence and 77% of patients who did not receive olaparib did not have recurrence. This new data is reflected in the updated guidelines.
For the patient who has finished treatment a year ago, this is where things get a little tricky in the real world. In the study you had to finish treatment within 12 weeks of starting olaparib, but what do you do with someone who is 4-5 months out, or a year? In this case, the data is less clear. There’s no one size fits all for a case like this. I think it’s worth an individual discussion with your oncologist to discuss if they think starting olaparib may be beneficial.
Can you speak to the recent news from the Monaleesa trials?
There are a series of Monaleesa studies looking at a drug called ribociclib. Ribociclib is in a class of drugs called CDK4/6 inhibitors, of which there are three FDA approved drugs for advanced breast cancer. All three have been shown to improve the time that it takes before a cancer starts growing, also called progression free survival. The Monaleesa2 study looks at ribociclib in combination with letrozole in first-line metastatic ER+ breast cancer. Patients either received letrozole alone or letrozole with ribociclib. The new data shows the overall survival was improved by greater than a year with the addition of ribociclib. The new data confirms adding ribociclib translates into an improvement in overall survival, which is always the gold standard in trials. It’s often very hard to demonstrate overall survival benefit in first-line therapy trials, especially for hormone positive breast cancer.
After taking a CDK4/6 inhibitor, what is next for ER/PR+ HER2- patients? I’m on palbociclib, but it stopped working. Can I move to ribociclib?
There’s data that shows some patients taking abemaciclib after palbociclib see a response. Currently, there are trials looking at patients who switch to abemaciclib after palbociclib or ribociclib. That’s because the targets in the cell that abemaciclib hits might be broader than palbociclib or ribociclib. I probably would not switch to ribociclib if you’ve progressed on palbociclib, but abemaciclib could be an option down the line. However, this is not in the FDA label or in the guidelines. This is based on published observational data.
Fulvestrant (Falsodex) is standard second line therapy in this case. This can be used in combination with other drugs. It’s fairly routine now to test patients for an alteration in a gene called PIK3CA because there is a drug called alpelisib (Piqray) that is approved for patients with that mutation. We see this in about 40% of ER+ patients so standard second-line therapy for those with the mutation has become fulvestrant with alpelisib. If a patient has a BRCA 1/2 mutation, then olaparib would be a very reasonable second line therapy. If you don’t have any of these alterations, fulvestrant can be given alone or with another therapy called everolimus, an mTOR inhibitor. At any point in treatment chemotherapy is an option. We also encourage patients to consider clinical trials.
Do you have experience with mistletoe injections improving the quality of life and overall survival in cancer patients being treated with traditional western therapies?
If my patients want to take herbal supplements like mistletoe because they feel it will make them feel better, as long as it does not negatively interfere or interact with the medications I prescribe, I often say it’s fine to take. This is more for quality of life.
As far as their benefit in treating the cancer, my concern is that for almost all of these supplements there are no randomized clinical trials to say whether or not these are helpful. It’s not to say it’s not worth asking the question, but I don’t think we can give an informed data-supported answer about the benefits of natural supplements in treating the cancer. I support my patients on natural supplements, but I can’t recommend them or comment on their effectiveness because I don’t think we have the data.
Do you have any lifestyle advice for patients that could help our treatments work better?
The two lifestyle areas where we have the best data are in exercise and healthy diet. The way I usually present this to patients is if everything goes well with your breast cancer, then heart disease becomes the next leading cause of health problems for women. It’s never too early to think about your heart and the things that are good for your heart are good for breast cancer like exercise and a healthy diet. I should add there’s a large study looking at aspirin as a potential way to further reduce risk of recurrence. There’s early retrospective data on this, but it’s not something I recommend right now but look forward to the study results.
What are some treatments on the horizon? What are you excited about?
I think selective estrogen receptor degraders (SERDs) are going to be terrific drugs. Depending on the study we’re seeing about 20%-30% of patients who develop resistance to anti-estrogen therapy develop mutations in the estrogen receptor itself and there’s early evidence that these drugs may still be active in this population. There’s hope that these drugs are going to be even more active than current anti-estrogen therapy.
I think we’ve only scratched the surface with immunotherapy. I think it’s terrific we have it now in TNBC. Identifying ways to make other breast cancer subtypes sensitive to immunotherapy is going to be an exciting path in the future.
I think the antibody drug conjugates are promising. Sacituzumab was a game changer for TNBC. There’s evidence that sacituzumab can be just as effective in ER+ breast cancer so I am hopeful we will see it used there. There are also drugs coming behind it that use the same target, but with potentially more effective chemotherapy binding partners or different targets with similar chemotherapy binding partners that could be active for ER+ breast cancer, HER2+ breast cancer and TNBC.
There are many molecules in the pipeline and every meeting we have lately we’re seeing really optimistic findings that have applications in the real world now.
There was some recent data from the DESTINY-Breast03 study. Can you tell us about that?
There was some really encouraging positive data presented at the ESMO meeting recently. The DESTINY-Breast03 study was a large clinical trial in metastatic HER2 positive disease for patients whose cancer progressed after first line treatment with a taxane and trastuzumab. Patients were randomized to receive either TDM1 (trastuzumab emtansine, Kadcyla) which is the standard second line therapy, or Trastuzumab deruxtecan (Enhertu). The study showed a remarkable improvement in progression free survival with a more than 70% reduction in risk of progression, as well as a more than doubling of the response rate from 34% to 80%. Although the data are still early, there was also a suggestion of improved overall survival too. This data hasn’t yet been published but I think this will make trastuzumab deruxtecan the standard second line treatment now. There are some risks with this drug, including potentially serious lung inflammation, but in this study the numbers were better than what had been reported previously, probably because oncologists are aware of these side effects and know how to manage them.
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