Case 3: Treatment After Progression in Triple-Negative Breast Cancer

Hope Rugo, MD, FASCO: Adam, in general, these patients progress. We’ve seen the PFS [progression-free survival] difference—a little more than 2 months. And the median survival, although 7 months greater, is still a little more than 2 years with rare exceptions. What do you do after patients progress on atezolizumab and nab-paclitaxel? And also, what are you offering the 60% of patients who were negative?

Adam Brufsky, MD, PhD: That’s a great question. At this point, all we have are the standard chemotherapies. We have eribulin, capecitabine, gemcitabine, carboplatin. If the patient’s BRCA mutation–positive, she’ll likely be offered a PARPinhibitor. I think there’s some exciting things, COVID-19 [coronavirus disease 2019] crisis or not, that will hopefully make their way into the public domain fairly soon. One that I’m particularly excited about is cusatuzumab.

While the phase 3 trial was not complete, the phase 2 data looked pretty good in women who had had a few prior lines of therapy for triple-negative disease. There was a reasonable response rate and a reasonable progression-free survival benefit. There are a lot of things on the horizon—cusatuzumab, in particular—that we can offer people who progress on atezolizumab and a nanoparticle, such as paclitaxel.

Hope Rugo, MD, FASCO: It’s an interesting question. There are also Akt inhibitors being tested, and we should see results from phase 3 trials as early as next year. As you mentioned, we hope to see regulatory approval this year, at some point.

There are other antibody drug conjugates that are being tested in triple-negative disease, which I think will be interesting as well. As we close about this particular case and move onto the next one, Ian, what is your thought about the neoadjuvant and adjuvant type of trials that are going on with checkpoint inhibitors? Do you think that’s going to be the way of the future?

Ian Krop, MD, PhD: I hope so. Just as Adam was saying, we don’t have a lot to offer our patients beyond chemotherapy right now in the metastatic setting, other than first-line checkpoint inhibition for a subset. We’re stuck with chemotherapy alone in the early disease setting as well, and we know that’s not adequate or sufficient for a lot of our patients. The data from the KEYNOTE studies showing a statistically significant improvement in pathologic complete response [pCR] of about 14% with the addition of pembrolizumab to standard neoadjuvant chemotherapy is encouraging. And even more so, this hint from the early readout of long-term outcome suggests there may be a benefit for the checkpoint inhibitor there as well.

What’s even more exciting is that it doesn’t even seem to be just in the patients who are PD-L1–positive. Both PD-L1–positive and PD-L1–negative patients seem to benefit, at least in the neoadjuvant setting with the use of pCR as an endpoint. We don’t know about that in terms of long-term outcome. To me, that’s the potential game changer in this field, and hopefully we’ll get the data as quickly as possible.

Hope Rugo, MD, FASCO: I think there is something about having both a more intact immune system and local disease versus de novo metastatic disease, where the tumor is relatively less resistant to therapy. I’m hopeful that this will make a really big difference, but I also think we’ve seen some data that suggest the chemotherapy that’s used is also really important.

I think what you said regarding HER2-positive disease really emphasizes the point we all feel strongly about. These patients should receive therapy in the neoadjuvant setting so we can better understand how treatment after surgery in patients who don’t have a pathologic complete response can alter outcome. We don’t know, but I think it’s a really critical lesson for all of us. These patients should be treated in the neoadjuvant setting if at all possible.

It’s exciting that we now have an option that may change outcomes for patients. Some of us have patients who have been on single-agent atezolizumab after dropping the chemotherapy following the approach of IMpassion130. Certainly, patients tire of chemotherapy eventually, so we continue them on their checkpoint inhibitor alone. I think my patient who’s the furthest out is just coming up on 1 year. That’s really striking for patients who had a 1.5-year median survival. Having the KEYNOTE-355 data, if we have patients who we can treat with effective therapy who relapsed at 6 months or more, that will also be really helpful. Adam, I think we’ll move onto the next case, but I just want to ask if you have any last comments?

Adam Brufsky, MD, PhD: No. I think this is an area where we had nothing a few years ago, other than chemotherapy, and now we’re going to have a lot of new things. That will be really exciting.

Hope Rugo, MD, FASCO: The 60% of patients who didn’t have PD-L1–positive disease are being addressed in a number of different studies that are looking at combining immunotherapy, or even giving chemotherapy as an induction and then adding in immunotherapy. Maybe we will see some improvements there as well.

Transcript edited for clarity.