PracticeUpdate: What are some of the key practice-impacting studies presented at this year's ASCO meeting? Could you start with the triple-negative space?
Dr. Kirshner: This 2020 virtual ASCO meeting was very important, at least from the point of view of a practicing clinical oncologist. There are at least three or four abstracts that were presented that are going to change the way we treat breast cancer almost immediately. I'd like to address each one of those abstracts. The first abstract was presented by Wang et al from China. They randomized patients with triple-negative breast cancer who completed adjuvant chemotherapy to either a year of capecitabine or placebo. There was a marked improvement in disease-free survival by over 10%. Now, the practice of care in our country, arguably, is to give neoadjuvant chemotherapy, but there are still many patients that receive adjuvant chemotherapy. There actually is one trial that is being completed in the U.S., but now we have an option for patients who present to us after receiving surgery. They're going to get the standard of care in terms of adjuvant chemotherapy, but they have an additional option, with capecitabine.
PracticeUpdate: What was practice changing for HER2-positive patients?
Dr. Kirshner: The next abstract, which addresses another aspect of breast cancer, is brain metastasis in HER2-positive patients. The FDA recently approved tucatinib as an additional agent to treat HER2-positive cancer. These patients frequently have brain metastasis, and Dr. Nancy Lin presented a study, subset of patients from that study, who had brain metastasis. What she found was that there was incredible activity with the systemic therapy when tucatinib was added. For patients that developed isolated metastasis or progression while they were on study, if they were treated locally and then were randomized to the tucatinib arm, those patients had increased progression-free survival also. This is a pretty big breakthrough because, traditionally, it's thought that patients with brain metastasis from breast cancer really don't respond to systemic therapy, but HER2-positive patients may be different. This is definitely going to change our practice.
PracticeUpdate: Was there anything practice-impacting for endocrine-positive patients?
Dr. Kirshner: The third abstract that was presented was using alpelisib for patients with the PIK3CA mutation. Right now, that drug is approved for patients with metastatic breast cancer to use… in conjunction with endocrine therapy. But it's only approved for patients that have not had CDK4 inhibition. We really don't know if it works as second-line therapy in patients that have progressed on those inhibitors, which, arguably, is the standard of care. We have this great drug, but in reality, there were very few patients that were really eligible for it. Dr. Hope Rugo did a multicenter study of 121 patients. It was a phase II study where the drug was added to fulvestrant. These patients had progressed on an aromatase inhibitor with CDK4 inhibitor, and there was a good response rate, and it was durable. The median progression-free survival in this poor prognosis set of patients was over 7 months.
Now, it was a phase II study. What they did – this is an interesting concept, and it's not really approved for principle – is they used the Flatiron platform and foundation testing to find similar patients who were treated without the alpelisib. These were patients that were just treated with fulvestrant. There was a significant improvement when compared to that control group. They had twice the response rate and duration of response. This is another option now for patients that progress on CDK inhibitors. Whether it's going to be FDA approved based on this one phase II study or not remains to be determined. There are additional studies in progress, but that looks very hopeful. I think for individual patients, we may be able to get the drug in this setting.
PracticeUpdate: Was there anything else that was practice-impacting in the metastatic or targeted setting?
Dr. Kirshner: Another very interesting abstract was presented by Dr. Nadine Tung. It was a multi-institutional study. We know that breast cancer patients with advanced disease who harbor a BRCA mutation, BRCA1 or BRCA2, respond relatively well to PARP inhibitors. They are actually approved for such patients. The question is, do patients with other germline mutations respond to PARP inhibitors? There have been isolated reports. And more importantly, or equally as important, does a mutation in the tumor itself that is BRCA1 and BRCA2… confer responsiveness to a PARP inhibitor? And how about the other mutations?
They looked at patients with hereditary breast cancer and other mutations, and they also looked at a subset of patients where the tumor was tested for mutations. What they found is that the PALB2-mutation patients had a high degree of responsiveness to the PARP inhibitors and the drug they used was olaparib. They had 11 patients with that mutation and all 11 had clinical benefit. Nine had a partial response and two had stable disease. Unfortunately, the other mutations, which may even be more common, such as the CHEK mutation, the ATM mutation, those patients didn't respond at all.
Now, when they looked at the next generation sequencing in the tumor, they also found that patients with BRCA mutations within the tumor responded to PARP inhibitors. That's been reported before, but they also found that the patients with PALB2 mutations responded also. What this means to me is that we should continue and maybe even expand testing of our breast cancer patients in terms of germline mutations that they inherit. Particularly for patients with metastatic disease who failed other therapies. I think it's very important to do the next-generation sequencing because there are other targets that can be found and now, we have an additional reason to test, to check for the BRCA mutations and PALB1 and other mutations that may respond to a PARP inhibitor.