PracticeUpdate Oncology February 2019

SABCS 2018 23

Subgroup Analysis of Combination Immunotherapy for Triple-Negative Breast Cancer

Interview with Alison K. Conlin MD by Farzanna S. Haffizulla MD, FACP, FAMWA Dr. Conlin is a Medical Oncologist at Providence Cancer Institute in Portland, Oregon.

And the summary is that it really matters still about the primary endpoint looking at the patients who have anti-PD-L1 on their immune cells. Those are the women who really benefit from this additional therapy of immune therapy and the rest of the immune biomarkers, really, you still needed to have the anti-PD-L1 on the immune cells to make it work. Dr. Haffizulla: So, just to quickly talk about that in the context of treatment decisions. Dr. Conlin: Sure. Dr. Haffizulla: Based on these results, which subgroup of patients will derive the most benefit, you’d say, from the addition of ate- zolizumab to nab-paclitaxel? Dr. Conlin: I think it’s clear that the patients have to have the anti- PD-L1 on their immune cells and that was about 41% of patients, so it’s not a small group. But those are the women who derive an overall survival benefit of 10 months, a progression-free survival benefit of several months, and it was statistically significant. And I think that’s where we’ll see this used. Dr. Haffizulla: So finally, for our clinicians viewing today, how can they use this data tomake treatment decisions for their patients? Dr. Conlin: Right. I think we’re waiting for the approval. So, I do feel like for first-line, triple-negative breast cancer we’re going to have to start testing all of our patients for PD-L1 status and then using this treatment for them as their first treatment. I think it’s very excit- ing news. Go to www.practiceupdate.com/c/77204 to watch this interview with Dr. Conlin.

Dr. Haffizulla: An important study this year at the San Antonio Breast Cancer Conference is the subgroup analysis of IMpassion 130. Can you remind us what this study was designed to evalu- ate and touch on the key findings? Dr. Conlin: Yeah. So, the IMpassion 130 study came out at ESMO this year, just a few months ago, and was very exciting as it’s the first study to show efficacy of immune therapy in breast cancer. And so, the study was looking at the addition in first-line treatment of triple-negative metastatic breast cancer of an immune therapy, anti-PD-L1 atezolizumab, to standard chemotherapy to affect sur- vival in these women. Dr. Haffizulla: What was the focus of the subgroup analysis pre- sented at this particular conference? Dr. Conlin: This study we were looking at the immune biomarkers. So, a really important question, “Does this work in everyone?” And we had already learned from the subgroup analysis prior reported that in patients who have anti-PD-L1 on their immune cells they clearly benefit from this treatment. And this was diving a little bit deeper and asking the question “Does it matter if you have anti- PD-L1 on your tumor cells, on your CD8 T-cells, on stromal TILs?”

" It’s a practice-changing study. What’s going to happen next week… is most of the patients, especially patients with a T2 or T3 tumor, larger than 2 cm or high-risk features, they will all be considered for neoadjuvant chemo, and then if they don't have a complete pathological response they will… receive T-DM1 in the adjuvant setting. "

patients who didn’t have a complete pathological response. So by looking at pathological response as a surrogate, we are selecting patients who are going to do better versus who may need something different. So here in the KATHERINE trial, if the patients had complete response they will continue to receive the trastuzumab, so they are not entered in the study. Patients who didn’t have complete response, they were randomized between trastuzumab and T-DM1. When the treatment is switched to something different, a novel mechanism of action, they did better with the T-DM1. Dr. Haffizulla: Can you explain the biologic rationale perhaps for the improved out- comes with this adjuvant T-DM1 rather than trastuzumab for these patients? Dr. Abraham: Probably if they have resid- ual disease, definitely there is an element of resistance, the tumor is resistant to the trastuzumab. So now you are bringing in antibody–drug conjugate which has a definitely different mechanism of action,

So T-DM1 is going to be the new standard in post-neoadjuvant setting for patients with residual disease. So as you said, all the future trials have to take that into account beforewe design a new trial.

potentially you are overcoming the resist- ance by introducing T-DM1. Dr. Haffizulla: Do the results of this particular trial raise any questions about other adjuvant strategies perhaps that might be considered for this same patient population? Dr. Abraham: Definitely. It’s a practice-chang- ing study. What’s going to happen next week on Monday is most of the patients, espe- cially patients with a T2 or T3 tumor, larger than 2 cm or high-risk features, they will all be considered for neoadjuvant chemo, and then if they don't have a complete patholog- ical response they will be random…oh, they will receive T-DM1 in the adjuvant setting.

Dr. Haffizulla is the Assistant Dean of Community and Global Health at Nova Southeastern University’s College of Allopathic Medicine. She practices general internal medicine in Davie, Florida, within her own internal medicine concierge practice.

Go to www.practiceupdate.com/c/77201 to watch this interview with Dr. Abraham.

VOL. 3 • NO. 1 • 2019