This podcast is made possible by the generous support of Lilly Oncology.
Maura Dickler: Hi! I’m Maura Dickler, and I’m vice president of Late Phase Oncology Research and Development at Eli Lilly. I am a breast cancer medical oncologist, and I practiced at Memorial Sloan Kettering for about 23 years, and I joined Eli Lilly in May of this year.
I’m attending the San Antonio Breast Cancer Symposium in 2018, and I think this is may be my 20th year of attending. It’s really been exciting to see the change and the growth. It’s really quite amazing.
This year, there are a number of interesting abstracts. When I think about new treatments in breast cancer, I often segregate them out into different classifications. When I’m thinking about immunotherapy in breast cancer, there’ll be an update of the atezolizumab study, which was a trial of abraxane or nab-paclitaxel with or without atezolizumab in women with metastatic triple-negative breast cancer. This was a first-line trial that was initially reported at ESMO this year in Munich, and it showed a benefit in overall survival, particularly in patients that had PD-L1-positive tumors. We anticipate an update of those results, and I think that the updated presentation will actually focus more on the immune biomarker subtypes, ultimately trying to find the subgroup of patients that benefit the most. So I anxiously await that presentation.
In the HER2-positive disease subtype, I think the biggest presentation this year is the KATHERINE trial. And that’s a study that’s looking at T-DM1 versus trastuzumab, and that’s in HER2-positive patients who have already received neoadjuvant chemotherapy but who have residual disease at the time of surgery. Patients with residual disease were randomized to either continue trastuzumab for a year of therapy or switch to T-DM1. I have to look once the data is presented and see how many patients got neoadjuvant pertuzumab, and I don’t think pertuzumab was continued after surgery, I think the comparison was T-DM1 versus [trastuzumab]. There was a press release that suggested that the benefit was in favor of T-DM1 and that it was a statistically significant benefit, so that may be a practice-changing abstract, although again, looking to see who got neoadjuvant pertuzumab and whether pertuzumab was continued for a year of therapy as in the APHINITY data will be important because ultimately doctors might opt for an APHINITY-type approach to treatment versus a KATHERINE-type approach. We’ll have to see and weigh the risks and benefits and side effects of those treatments.
Also in the HER2-positive space, there’s an update of the PHARE trial, and that was looking at the duration of trastuzumab, either 6 versus 12 months, in a lower-risk population of patients. The KATHERINE trial is a high-risk population of patients who have residual disease after neoadjuvant treatment. The PHARE trial was just an adjuvant study, and I look forward to seeing those results.
I think the duration of trastuzumab is important especially in women who have a reduction in their left ventricular ejection fraction during treatment. That sometimes happens when women are getting anti-HER2 therapy, and sometimes we have to stop the trastuzumab early. Data showing that 6 months of treatment might be sufficient is often reassuring for the women who can’t complete a year of therapy. Presently, 1 year of trastuzumab is the current standard of care.
There will also be an update of the SOLAR trial. That was a study that looked at alpelisib in combination with fulvestrant in women with ER-positive, HER2-negative metastatic breast cancer. The primary endpoint of that trial was to see if alpelisib added to the benefits of fulvestrant in a PIK3CA-mutant population of women, although there was a broader group of patients that were treated, so there was a mixture of PIK3CA-mutant positive and negative. But again, the primary endpoint was in the mutant population. That study was also presented at ESMO, and it was positive in favor of the addition of alpelisib in the mutant population. At San Antonio we’ll be seeing an update of that data and more subgroup analyses.
And then finally in the CDK4/6 inhibitor space, there are no practice-changing abstracts but there are some interesting abstracts. There’s a study looking at trilaciclib in combination with gemcitabine and carboplatin in metastatic triple-negative breast cancer. This is a different trial, actually, in that this is not the typical ER-positive, HER2-negative metastatic disease the way we’ve seen the three CDK4/6 inhibitors tested. This is actually given in combination with chemotherapy in the hopes that it’s given first to pull the bone marrow cells out of cell cycle so that the myelosuppressive effects of chemotherapy are diminished. This study, according to the abstract, looks like it was beneficial in terms of protecting the myeloid precursors, lessening neutropenia, and we’ll see outcome data.
There is a study of the next MONARCH trial, which is abemaciclib in combination with tamoxifen, also some arms as a single agent, which is of interest.
Then there’s the PALLET trial, which is a study looking at palbociclib in combination with letrozole in the neoadjuvant setting. So that’s a grouping of interesting presentations that are here. I’d say the most practice-changing is likely to be the KATHERINE trial, but I look forward to seeing updates from some of the large trials that were presented initially at ESMO.
Editor’s Note: On May 24, 2019, the U.S. Food and Drug Administration approved Piqray (chemical name: alpelisib) in combination with Faslodex to treat metastatic and advanced-stage, hormone-receptor-positive, HER2-negative breast cancer with a PIK3CA mutation that has grown after hormonal therapy treatment in postmenopausal women and men.
