Erica L. Mayer, MD, PhD, on Metastatic Breast Cancer: New Findings on Palbociclib After Prior CDK4/6 Inhibitor and Endocrine Therapy
2022 San Antonio Breast Cancer Symposium
Erica L. Mayer, MD, PhD, of Dana-Farber Cancer Institute, discusses findings from the PACE study of patients with endocrine- and CDK4/6 inhibitor–pretreated estrogen receptor–positive/HER2-negative metastatic breast cancer who were randomly assigned to fulvestrant alone; fulvestrant and palbociclib; or fulvestrant, palbociclib, and avelumab. Combining palbociclib with fulvestrant beyond disease progression on a prior CDK4/6 inhibitor regimen did not improve progression-free survival compared with fulvestrant alone. A longer progression-free survival when a PD-L1 inhibitor was added to fulvestrant and palbociclib deserves further study. A baseline circulating tumor DNA analysis suggests that the potential benefit of palbociclib after progression on a prior CDK4/6 inhibitor may be influenced by ESR1 or PIK3CA status (Abstract GS3-06).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The combination of a CDK4/6 inhibitor and endocrine therapy has been a standard-of-care in the management of metastatic hormone receptor positive, HER2 negative breast cancer. Patients can do very well, but eventually resistance develops and progression. And then the question is, what do we do next? A big question has been, is it appropriate to continue CDK4/6 inhibition with a change in endocrine therapy or to stop CDK4/6 inhibition? The PACE Trial, which is a randomized phase 2 trial, was designed to address this question. Eligible patients for the PACE Trial had metastatic hormone receptor-positive/HER2-negative breast cancer, and had received a CDK4/6 inhibitor and endocrine therapy containing regimen, for at least six months of disease stability indicating endocrine resistance. Patients could have up to two lines of endocrine therapy, no prior fulvestrant and up to one prior line of chemotherapy.
Patients were randomized into one of three arms, fulvestrant alone, which we can think of as a control arm, fulvestrant with palbociclib, so continuation of a CDK4/6 inhibitor or a third arm of fulvestrant palbociclib and the PDL1 inhibitor, avelumab, a triplet combination which is based off of preclinical data. A total of 220 patients in the United States enrolled on the PACE Trial and results from this study which have been presented, demonstrated to us that continuation of the CDK4/6 inhibitor using palbociclib in combination with a change to fulvestrant, did not prolong progression-free survival compared to staying on fulvestrant alone. The median progression-free survival was 4.6 months with fulvestrant and palbociclib, and 4.8 months with fulvestrant alone. Interestingly, the triplet arm of fulvestrant, palbociclib and avelumab, had practically doubled progression-free survival at 8.1 months. Overall, this was a well-tolerated regimen. There were no unexpected toxicities and importantly in that triplet immunotherapy arm, there were no excessive immune related toxicities.
I think we can learn several things from this study. First of all, what we learned is that four patients who have been receiving a CDK4/6 inhibitor, which in this study was mostly palbociclib, if their disease progresses, continuing palbociclib beyond progression, was not shown to be helpful in the PACE Study, so we want to look into other options. But there are a lot of other options that are coming out for these patients, a wealth of options. This includes perhaps other CDK4/6 inhibitors such as ribociclib. There's palpolicib for patients with PIK3CA mutations. There's everolimus. Recently we've heard exciting data with capivasertib. We can offer oral surds, which are in development. There's PARP inhibitors for patients with BRCA mutations, so lots of different choices that are available for our patients and we look forward to more data that will help clarify what's the best option for patients in this situation.
Yara Abdou, MD, of the University of North Carolina, discusses results from the RxPONDER SWOG S1007 study, which showed that non-Hispanic Black women with hormone receptor–positive/HER2-negative breast cancer with one to three involved lymph nodes and a recurrence score of ≤ 25 have worse outcomes than non-Hispanic White women. In addition, Black patients were more likely to accept treatment assignment than their White counterparts and were just as likely to remain on estrogen therapy at 6 and 12 months, suggesting that outcome differences may be less likely attributable to lack of treatment compliance within the first year (Abstract GS1-01 ).
Joseph A. Sparano, MD, of the Tisch Cancer Center at Mount Sinai Health System, discusses long-term clinical outcomes data that continue to show many women with early breast cancer can safely forgo chemotherapy, when guided by the 21-gene recurrence score result. The longer follow-up also showed that recurrences of breast cancer continue to occur years after the original diagnosis, although these recurrences were not prevented by chemotherapy use. Racial disparities were not explained by inequities in social determinants of health or treatment adherence, with Black women at higher risk of early recurrence within the first 5 years of diagnosis, but not later recurrence after 5 years (Abstract GS1-05).
Nicholas C. Turner, MD, PhD, of London’s Institute of Cancer Research and The Royal Marsden, discusses phase III results from the CAPItello-291 clinical trial, which showed that in patients with hormone receptor–positive, HER2-negative tumors resistant to aromatase inhibitors, adding the investigational AKT inhibitor capivasertib to fulvestrant doubled the median progression-free survival compared with placebo plus fulvestrant (Abstract GS3-04).
Marleen Kok, MD, PhD, of the Netherlands Cancer Institute, discusses the most important advances in early breast cancer treatment during the past year for patients with triple-negative, HER2-positive, and estrogen receptor–positive disease. Dr. Kok also addresses long-term treatment toxicities and quality of life.
Ruth O’Regan, MD, of the University of Rochester Medical Center, discusses the Breast Cancer Index (BCI), a genomic assay that can assess the risk of late distant recurrence (5–10 years after diagnosis) of hormone receptor–positive, early-stage breast cancer. Among premenopausal women with this disease who were enrolled in the SOFT trial, those with a high BCI score had an increased risk of distant recurrence. Those with a low BCI score benefited more from the addition of ovarian suppression therapy to endocrine therapy after 12 years of follow-up (Abstract GS1-06).