New: NCI-funded clinical trial search
Mednet Logo
Community

What are your top takeaways in Breast Cancer from ASCO 2022?

What were your “top 3” presentations/studies coming out of the meeting this year and how will it impact your own clinical practice?
12 Answers
Mednet MemberInvited Expert
Radiation Oncology · Varian Medical Systems/Allegheny health network
Answered on
  1. DESTINY-Breast04: it is phase III study of Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice in HER2-low metastatic breast cancer (MBC). This study showed improved progression-free survival (PFS) and overall survival (OS) with T-DXd vs standard therapy in this patient population. T-DXd is already SOC for MBC HER2 neu positive breast cancer and now this study establishes it as a new standard of care for HER2 neu low MBC. 
  2. NRG-BR002: it was a negative trial of SBRT/local treatment for oligometastases for breast cancer with no difference in progression-free or overall survival. Elsewhere metastasis rate was similar in both arms. We may need better selection criteria in future trials to identify if any subset of patients with metastatic breast cancer would benefit from local therapy.
Mednet MemberInvited Expert
Medical Oncology · Ohio State University Wexner Medical Center
Answered on
  1. DESTINY-Breast-04 is practice changing. In this study, the novel antibody-drug conjugate Trastuzumab deruxtecan outperformed physicians' choice of chemotherapy for patients with pretreated, metastatic HER2 low expressing breast cancer (IHC 1+ or IHC 2+ with negative FISH). There was a significant improvement in both progression-free survival (9.9 months vs 5.1 months, respectively,) and overall survival (23.4 months vs 16.8 months, respectively).
  2. The Sharma study shows the potential to have an anthracycline-free neoadjuvant chemotherapy regimen in PD-L1 positive, triple negative breast cancer. In this study, patients who received Taxotere + Carboplatin AUC 6 + Pembrolizumab had a pathologic complete response rate of 58% and 2-year disease-free survival of 89%, which is comparable to clinical outcomes seen with KEYNOTE-522 (pCR 65% and 3 year EFS 84.5%). The benefit was much stronger in PD-L1 positive patients, which is estimated to be around 60% of patients with early stage TNBC.
  3. PALOMA-2: Survival benefit of Palbociclib is now unclear in metastatic ER+ breast cancer. The PALOMA-2 study results showed no significant improvement in overall survival compared to Letrozole therapy alone. As noted by the investigators, both arms had significant missing data (13% in Palbociclib arm vs 21% in placebo arm) but this is still concerning. Given the recently reported positive survival data for Riboclclib in the MONALEESA-2 trial (Hortobagyi et al., PMID 35263519), this raises questions regarding the optimal CDK4/6 inhibitor in the metastatic setting. It is unclear at this time if patients should be changed from Palbociclib to Ribociclib.
Mednet MemberInvited Expert
Radiation Oncology · Beth Israel Deaconess Medical Center
Answered on
  1. Whelan T et al. LUMINA: A prospective trial omitting radiotherapy (RT) following breast conserving surgery (BCS) in T1N0 luminal A breast cancer (BC). (abstr LBA501) - The LUMINA single-arm prospective trial found that the local recurrence rate at 5 years was 2.3% following partial mastectomy and endocrine therapy without RT among 501 selected patients (age 55 years or older; grade 1-2; T1N0; 1mm or wider margins; "Luminal A" subtype defined as ER 1% or greater, PR greater than 20%, HER2 negative, and Ki67 13.25% or less), with median follow-up of 5 years. This recurrence rate is likely to double by 10 years but is still likely to be acceptable to most patients. These results confirm the effectiveness of this approach, as shown already by multiple studies. I will be very interested in subgroup analyses in relation to patient age, tumor size, and exact margin width and their combinations. This trial also suggests that expensive genomic assays such as Oncotype DX testing (used in the single-arm IDEA trial and the NRG randomized DEBRA trial) may not be needed to adequately select such patients, though performing accurate Ki-67 measurements is not a trivial issue.
  2. Chmura S et al. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). (abstr 1007) - The NRG-BR002 phase II randomized trial compared outcomes with systemic therapy alone or systemic therapy plus SBRT or resection of all sites of disease among 125 patients with 3 or fewer sites of metastatic disease who had controlled primary disease who had been on systemic therapy for 12 months or less without progression. About 79% of patients were ER or PR positive and HER2 negative. With median follow-up of 30 months, the 36-month overall survival rates in the two arms were 72% and 69%, respectively; 36-month progression-free survival rates were 33% and 38%, respectively. Neither difference was statistically significant. They decided not to go forward with a much larger phase III trial because of the negative results. I will be interested to see if the subgroup analyses suggest that some patients might benefit from ablative therapy, but for now, these results strongly argue against using SBRT for asymptomatic oligometastases in patients with breast cancer.
  3. Hamilton EP et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) unresectable and/or metastatic breast cancer (mBC): Safety follow-up of the randomized, phase 3 study DESTINY-Breast03. (abstr 1000) - The DESTINY-Breast03 trial comparing Trastuzumab deruxtecan (T-DXd) to Trastuzumab emtansine (T-DM1) in patients with HER2 low-expression (1+ or 2+ on immunohistochemistry) metastatic disease who had received one or two prior chemotherapy regiments showed the former drug to be substantially more effective than the latter for patients as measured by median progression-free survival (16.1 versus 6.9 months, respectively) and overall survival (23.4 months and 16.8 months, respectively). The results were published in the New England Journal of Medicine on June 5, 2022. The results potentially affect a large patient subgroup and are likely to lead to trials in the adjuvant setting. What is not yet clear is how this drug can be integrated with RT. One toxicity of note was pneumonitis, which occurred in 12% of patients in the T-DXd arm. I have not yet seen any case reports or other studies on whether RT increases this risk. For now, at least, it would certainly seem best to avoid giving RT concurrently with T-DXd. I do not know long we should advise our medical oncology colleagues to wait before starting T-DXd after RT, but my usual rule of thumb is at least 2 weeks if possible for other chemotherapy drugs.
Mednet MemberInvited Expert
Medical Oncology · Ohio State University
Answered on
  1. DESTINY-Breast04 - Takeaway: Clinically meaningful OS benefit and superior ORR over SOC chemotherapy in previously treated HER 2 low MBC (HER 2 IHC 1+ or 2+ with negative FISH) MBC. This makes TDxd a suitable treatment choice for a vast majority of patients with MBC independent of receptor subtype. Toxicities are consistent with previous studies with a 10-12% rate of ILD, mostly G1, 2. While clearly practice changing, this study raises a critical need for biomarkers (IHC can miss several potential candidates) to define HER 2 low tumors for treatment benefit. It is important to note that HER-2 low expression does not represent a distinct biologic subtype.
  2. MAINTAIN - Takeaway: Smaller yet brilliant RP2 study design demonstrating that 2nd line Ribociclib along with switching ET (predominantly to fulvestrant) shows meaningful clinical benefit in PFS in a subset of patients with HR + HER 2 negative MBC experiencing initial disease progression on front line CDK 4/6i + ET. This is consistent with RWD findings reported by Wander et al., PMID 33761455 showing clinical benefit of abemaciclib + ET in patients previously receiving palbociclib, however, most patients did not receive sequential CDK4/6i therapy in this series. One important question for clinical applicability is how this approach fits in a crowded space of novel upcoming therapies such as SERD/SERD combination, IO combinations, PI3K or AKT inhibitors, etc. to name a few. Moving forward, I may consider this approach for a few select patients (ESR1 and PIK3CA WT and switching ET to fulvestrant rather than AI).
  3. LUMINA - Takeaway: Omitting adjuvant radiotherapy in post-menopausal women with pT1N0 ER positive HER 2 negative BC with low KI 67 in this single arm multi center Ph2 study shows a very low event rate of 2.3% cumulative LRR incidence at 5 years of follow up. This demonstrates the feasibility of this approach for appropriate women with low-risk BC undergoing BCS and committed to taking at least 5 years of adjuvant endocrine therapy.  The ongoing NRG randomized PH3 DEBRA (NCT04852887) trial tests a similar hypothesis evaluating time to IBTR with the omission of adjuvant radiotherapy compared to current SOC in both pre- and post-menopausal women with pT1N0 HR positive HER 2 negative BC undergoing BCS with low Oncotype RS< 18. All in all, represents a step forward in appropriately personalizing therapy based on risk, thus avoiding unnecessary toxicities, and optimizing QOL and health care costs. 
Mednet MemberInvited Expert
Medical Oncology · University of Texas MD Anderson Cancer Center
Answered on
  1. LBA3 - Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. One of the biggest benefits we have ever seen in HR+ disease where in later lines of chemotherapy, responses tend to be quite short. Can this drug be used earlier or even in the adjuvant/neoadjuvant setting eventually? I will go a little off the rails for studies that I think will be important (but not immediately impactful) for HR+/HER2-neg advanced breast cancer that is an area of great need given the long-term risk of recurrence for early stage and the indolent, yet ultimately unresponsive situation in advanced setting and its commonality
  2. Abtr. 1005 - Fulvestrant plus capivasertib versus fulvestrant plus placebo after relapse or progression on an aromatase inhibitor in metastatic, estrogen receptor–positive breast cancer (FAKTION): Overall survival and updated progression-free survival data with enhanced biomarker analysis. While it is early in the understanding of AKT inhibition, we already have a good understanding of the genomic profiles of responsive candidates – this is very helpful information to have before a drug becomes available.
  3. Abstr. 504 - Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. Potentially very important framework to know early on how to use personal therapy with molecular profiling to bend the curve for HR+/HER2-neg breast cancer, which typically has a constant hazard of recurrence over one’s lifetime, and in the metastatic setting, progression even after long periods of control, but ultimately, few options after successive courses of therapy and few guiding biomarkers.
Mednet MemberInvited Expert
Medical Oncology · Medical College of Wisconsin
Answered on
  1. DESTINY-Breast04: which showed PFS benefit of Trastuzumab deruxtecan over traditional chemo in HER2 low positive (IHC +1, +2 but FISH negative) patients. This study expands the use of Trastuzumab deruxtecan to another 50% of patients who normally will not be offered an anti-HER2 therapy.
  2. MAINTAIN trial which showed PFS benefit of Ribociclib in ER/PR+, HER2- metastatic breast cancer patients who failed one of the CDK 4/6 inhibitors. This study showed that not all three CDK 4/6 inhibitors are the same and they could be used one after another one. This adds another treatment option to those who fail one CDK 4/6 inhibitor.
  3. The use of Sacituzumab in ER/PR+, HER2 - metastatic breast cancer which showed PFS benefit compared to chemotherapy alone. This study expands the use of Sacituzumab to another large group of metastatic breast cancer patients (ER/PR+, HER2-) besides the triple negative one.
Mednet MemberInvited Expert
Medical Oncology · Yale
Answered on
  1. DESTINY-Breast04 - We will have a new systemic therapy option for those with HER2 low disease which is urgently needed.
  2. LUMINA study - Important that we can possibly de-escalate radiation in patients 55 and older with luminal A tumors.
  3. KEYNOTE 522 and RCB analysis - Important additional analysis showing the benefit of immunotherapy in those with RCB 2 and 3.
Mednet MemberInvited Expert
Medical Oncology · University of North Carolina at Chapel Hill
Answered on
  1. DESTINY-Breast04: Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice in patients with HER2-low metastatic breast cancer. This is the first phase 3 trial of HER2-directed therapy in patients with HER2-low metastatic breast cancer to show a statistically significant and clinically meaningful benefit in PFS (~5 months) and OS (~6.6 months) compared to standard-of-care treatment, regardless of hormone receptor status. These impressive results are practice changing and will definitely change the standard of care for patients with HER2-low breast cancer. It is time for us to define HER2-low as a distinct therapeutically targetable subgroup in breast cancer.
  2. TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients with heavily pretreated HR+/HER2- advanced breast cancer. SG showed a statistically significant improvement in PFS compared to TPC, which was most notable at 12 months (21% vs 7% respectively), although median PFS only showed a 1.5m benefit, which arguably can be considered less clinically meaningful. Overall survival data is still immature. While this is not practice changing data, these results suggest a potential for SG to improve outcomes in a heavily pretreated population with unmet clinical needs.
  3. MAINTAIN: This study showed that patients with HR+/HER2- metastatic breast cancer who received Ribociclib after progression on CDK 4/6i (and switched endocrine therapy) had a significant PFS benefit and improved CBR. Exploratory analysis in the fulvestrant subgroup suggests that this benefit is limited to ESR1 WT tumors. Although this is not practice changing, it is an important study given it’s the first randomized trial showing benefit in CDK4/6i/post-CDK4/6i. Several other trials are looking at this important question; postMONARCH, PALMIRA, PACE. 
Mednet MemberInvited Expert
Medical Oncology · Sarah Cannon Research Institute
Answered on
  1. DESTINY-Breast04 is quickly actionable. IHC was designed to identify the HER-2 high (IHC 3+) for trastuzumab. Was never for identifying 0 from 1+. A lot of variability here. Need to discuss 1+ as being actionable with our pathologists. Many I have talked to think that most tumors will have 1+ within certain areas of tumor. 
  2. Overarching theme of ADCs - HER-3, HER-2, Trop-2, etc. Big need will be sequencing and determining which ADCs work after each other and how to order.
  3. KN522 - it’s not ALL about the pCR. RCB 0 and 1 patients do quite well. Pembro also benefited patients in terms of recurrence across RCB categories.
Mednet Member
Medical Oncology · Washington University School of Medicine
Answered on
  1. DESTINY-Breast04 - TDxd clearly much better with impressive clinically relevant differences over TPC (capecitabine, eribulin, gemcitabine, taxane) in both ER+ and TNBC cohorts. Although the numbers with TNBC were small, the results were equally impressive in this cohort of 60 patients. Results are also despite patients being heavily pretreated with a median of 3 lines of systemic therapy. This should now be immediately considered as SOC for eligible patients.
  2. Ph1/2 study of patritumab deruxtecan in HER3+ MBC - Encouraging results with ORR of 30% in ER+, 23% in TNBC, and 43% in HER2+ pretreated patients. ILD rates of 7%, lower than other ADCs, but more studies awaited.
  3. MAINTAIN - This study adds to emerging data that all 3 CDK4/6i on the market are not equal. Despite 87% having previously received palbociclib, the pry endpoint showed a PFS of 5.29 versus 2.76 months (HR 0.57) with switching to ribociclib following palbociclib. Taken together with the lack of OS data with palbociclib, I suspect this may begin to shift the current landscape regarding use of CDK4/6 inhibitors.
Mednet MemberInvited Expert
Medical Oncology · Washington University School of Medicine
Answered on
  1. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study - The significant improvement in PFS and OS comparing T-DXd and SOC chemotherapy for patients with metastatic HER2-low breast cancer who progressed on prior lines of chemotherapy is impressive and the results are practice changing.
  2. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer - The study showed a statistically significant and clinically meaningful PFS benefit over SOC chemotherapy in heavily pre-treated HR+/HER2- endocrine resistant advanced/metastatic breast cancer, offering another attractive option for this population who has limited treatment options.
  3. LUMINA: A prospective trial omitting radiotherapy (RT) following breast conserving surgery (BCS) in T1N0 luminal A breast cancer (BC) - The study presents a de-escalation option to omit radiation therapy for women ≥ 55 years with grade 1-2 T1N0 luminal A BC following BCS treated with endocrine therapy alone.
Mednet MemberInvited Expert
Medical Oncology · UT Health San Antonio
Answered on
  1. DESTINY-Breast04: the role of T-DXd in the treatment of HER2 low breast cancer: practice changing trial showing that patients with tumors Her2 1+ and 2+ can benefit from the use of T-DXd.
  2. TROPiCS-02: the role of sacituzumab govitecan in patients with metastatic ER+ breast cancer showing that this agent outperformed chemotherapy in this patient population. Again practice changing.
  3. HER3-DXd: this is a novel anti HER3 ADC showing activity in patients with HER3 positive breast cancer. This agent is not available yet but it showed good preliminary efficacy and future trials will be performed to determine its role in the treatment of breast cancer.