Nancy Davidson, MD: In It for the Long Haul: Outcomes in Hormone Receptor–Positive Breast Cancer
2022 ASCO Annual Meeting
Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, reviews results from four abstracts about the importance of long-term follow-up in studies of adjuvant endocrine therapy for hormone receptor–positive breast cancer. Because the natural history of hormone receptor–positive breast cancer is long, an effort is underway to improve selection of patients by clinical parameters or biomarkers, refine the endocrine therapy background, and administer more effective combinations of endocrine therapy with other agents.
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
One of the vexing problems in the management of hormone receptor positive breast cancer is that patients still relapse. We know a lot about the natural history of the disease, and we know that sometimes the relapses can be later. So, we had the opportunity recently to hear the results of four clinical trials that try to look at longer term outcomes in hormone receptor positive breast cancer. These trials in my estimation, try to tackle a couple of different ways that we could improve on this situation. In some cases, they try to refine the selection of patients either by clinical parameters or by molecular tests. In other cases, they try to look at combinations of endocrine therapy or sequences of endocrine therapy. In some cases, they also take a look at the addition of other agents to endocrine therapy. And then finally, we sometimes look at the duration of endocrine therapy.
Now, the first trial that I want to talk about in this context is that a retrospective analysis of the trials from the IBCSG looking at the big trial, the soft trial, and the text trial. This reanalysis was done of this trial, these trials, to try to look at the subsets of high risk patients within those trials, those who had node positive disease or node greater than four nodes, or one to three positive nodes with high risk features. And that's because we wanted to look at them in the context of some of the CDK4/6 inhibitors trials that have also emerged. What came out is that there is an advantage of the endocrine therapy in these trials over the long haul. It also provides us with a baseline, so that we can use this in the future for trial designs for addition of new agents. Wonderful to see that long term follow up.
A second trial looked at older patients. Now this is a really unmet need in early stage breast cancer. This trial focus specifically on patients 70 or over, and it looked at a genomic index as a way of trying to select for or against the use of chemotherapy in addition to endocrine therapy. This genomic index hasn't really been used elsewhere and this trial did show at the end of the day that this index did not help to select for or against the use of chemotherapy. The patients that had high genomic index didn't do better with the chemotherapy. So, as a consequence, we won't be using it further but congratulations to them, we're focusing on high risk elderly patients. Another trial looked at ovarian function suppression in the context of tamoxifen. Long follow up again, it supports the use of ovarian function suppression as we've done in the past, but only two years actually. So, an effort to try to deescalate the ovarian function suppression, wonderful to see that long term follow up.
And then finally the last trial looked at whether or not we should use Denosumab, a bone strengthening agent in addition to hormone therapy in postmenopausal receptor positive breast cancer. We already know that this can help to decrease fractures and what the long term follow up of this trial has shown and exploratory endpoints that Denosumab also decreases the risk of recurrence of breast cancer and appears to also help with survival. So, this may in fact help us to think about whether or not we should use Denosumab to both maintain bone health and as a form of adjuvant therapy in this very select patient population that is postmenopausal women with receptor positive breast cancer, who are receiving aromatase inhibitors. And some these trials really support the notion that we must have longterm follow up for hormone receptor positive breast cancer patients when we're looking at these endocrine therapies and I applaud all four trialists for bringing us to the conclusion.
Nabil F. Saba, MD, of Winship Cancer Institute of Emory University, discusses new data from a trial of pembrolizumab and cabozantinib in patients with recurrent metastatic head and neck squamous cell carcinoma. The study met its primary endpoint of overall response rate. The regimen was well tolerated and exhibited encouraging clinical activity in this patient population (Abstract 6008).
Gilberto de Lima Lopes, Jr, MD, MBA, of Sylvester Comprehensive Cancer Center at the University of Miami, and Oladimeji Akinboro, MD, MPH, of the U.S. Food and Drug Administration (FDA), discuss a data analysis, which suggests that most subgroups of patients with advanced non–small cell lung cancer with a PD-L1 score of 50% or greater who are receiving FDA-approved chemotherapy/immunotherapy regimens may have overall survival outcomes comparable to or better than immunotherapy-alone regimens (Abstract 9000).
Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute, and Ian E. Krop, MD, PhD, of Yale Cancer Center, discuss phase I/II findings on patritumab deruxtecan, a HER3-directed antibody-drug conjugate, in patients with HER3-expressing metastatic breast cancer. A pooled analysis showed antitumor activity in women with HR-positive/HER2-negative and HER2-positive advanced disease, as well as triple-negative breast cancer (Abstract 1002).
Mairéad G. McNamara, PhD, MBBCh, of The Christie NHS Foundation Trust, discusses phase II findings of the NET-02 trial, which explored an unmet need in the second-line treatment of patients with progressive, poorly differentiated extrapulmonary neuroendocrine carcinoma. In the trial, the combination of liposomal irinotecan, fluorouracil, and folinic acid, but not docetaxel, met the primary endpoint of 6-month progression-free survival rate (Abstract 4005).
Bradley J. Monk, MD, of the University of Arizona College of Medicine and Creighton University School of Medicine, discusses phase III findings from the ATHENA–MONO (GOG-3020/ENGOT-ov45) trial. It showed that rucaparib as first-line maintenance treatment, following first-line platinum-based chemotherapy, improved progression-free survival in patients with ovarian cancer, irrespective of homologous recombination deficiency status (Abstract LBA5500).