Our team was in Texas last week, attending and exhibiting at the San Antonio Breast Cancer Symposium. This annual event brings together the world’s leading breast cancer researchers, clinicians, and advocates. Every year, the latest advancements in breast cancer research, treatment, and patient care are announced at this key industry event. We were fortunate to host numerous focus groups and meet so many patients while at the conference!
For our patient members who weren’t onsite in San Antonio, here’s our recap of the news announced at the conference that we believe is most relevant to members of our community.
MBC (stage 4) research updates from SABCS 2023
This phase 3 trial offered patients with a PIK3CA mutation a triplet therapy of inavolisib in combination with fulvestrant (Faslodex) and palbociclib (Ibrance) vs. palbociclib and fulvestrant alone. It showed a clinically meaningful progression-free benefit of 15 vs 7.3 months. This trial looked specifically at how well this drug combination worked in a first line for patients who experienced a recurrence while on endocrine therapy or within 12 months of stopping their hormone therapy. The pivotal study findings for the Inavolisib combination could signify a significant breakthrough for individuals with PIK3CA-mutated, HR-positive breast cancer, offering a well-tolerated initial treatment option.
The phase 3 HER2CLIMB-02 trial found that combining two HER2-targeted drugs, tucatinib (Tukysa) and trastuzumab emtansine (Kadcyla, T-DM1), extended progression-free survival among patients with unresectable locally advanced or metastatic HER2-positive breast cancer, compared with T-DM1 alone. There was improvement shown in both patients with and without brain mets at baseline, however more significant (36% vs. 24%) reduction in risk of progression-free survival or death for those with brain mets at baseline vs. the overall study cohort. This is of particular significance as it presents another treatment option for HER2-positive patients who have brain metastases, which is currently an area with limited treatment options.
Results from the phase 3 TROPION-Breast01 trial confirmed the benefits of the Trop2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) for patients with HR+/HER2- metastatic breast cancer. Patients in the study had to have progressed on a prior endocrine therapy and received at least one or two lines of prior chemotherapy. The median progression-free survival for patients given Dato-DXd during the trial was 6.9 months compared to 4.5 months on standard chemo treatment. While there are quite a few treatment options available for HR+/HER2- breast cancer currently, this study offers patients with this diagnosis a potential non-chemotherapy treatment option with significantly less side effects reported compared to the standard of care arm.
For patients with resistant hormone receptor positive (HR+)/HER2- breast cancer and triple-negative breast cancer, the oral multikinase inhibitor Tinengotinib was found to have clinical benefit and manageable side effects in a phase 1 study. These study findings may be of particular interest to patients with metastatic breast cancer who have been on multiple lines of therapy. The median number of prior therapies for study participants was 5. As this is a phase 1 study, the overall aim was to assess tolerability and dose escalation. Further studies need to be done to compare this treatment with others.
Combination therapy with anastrozole (Arimidex) or fulvestrant (Faslodex) plus fam-trastuzumab deruxtecan-nxki (Enhertu) demonstrated encouraging antitumor activity for patients with HER2 – low/hormone receptor positive tumors, who have not received prior treatment with chemotherapy. This was a phase 1 study, so the primary endpoint was safety and tolerability. More studies need to be done to examine other outcomes and compare results against current standard of care treatment.
Results from the phase 1b/2 ELEVATE and ELECTRA clinical studies evaluating elacestrant (ORSERDU) in combination with other treatments for ER+ metastatic breast cancer found predictable and positive initial safety results as well as “promising preliminary efficacy data.” A challenge that patients with ER+ metastatic breast cancer often face is treatment resistance. Elacestrant is currently approved as a single agent for ER+/HER2-negative, ESR1-mutated advanced or metastatic breast cancer. These studies both aim to provide data in support of additional combination therapy options for this population in the face of resistance.
EBC (stages 1-3) research updates from SABCS 2023
The phase 3 IDEA trial aimed to test whether certain low-risk patients may be able to skip adjuvant radiation to the axillary lymph nodes. The study, which enrolled patients between 50 and 69 years of age who had stage 1, HR-positive, HER2-negative breast cancer, compared outcomes between groups who underwent whole breast radiation vs. whole breast plus chest wall and lymph nodes, following a complete response with neo-adjuvant chemotherapy. The results found that younger postmenopausal patients with early-stage breast cancer may be able to safely forgo adjuvant radiotherapy, providing they had a low OncotypeDX recurrence score and a complete lymph node response to pre-surgery chemotherapy. Among study patients eligible to skip radiation, 100% were alive five years after surgery and 99% (184 patients) were breast cancer free at this time. This is significant for patients as it highlights an option for less intense treatment for eligible patients.
This phase 3 study previously reported interim findings highlighting the addition of pembrolizumab (Keytruda) to neoadjuvant (before surgery) chemotherapy followed by adjuvant (after surgery) pembrolizumab significantly increased pathologic complete response (pCR) and event-free survival vs. neoadjuvant chemotherapy alone in patients with early-stage triple-negative breast cancer. This led to the initial FDA approval for this regimen in 2021. The update at SABCS 2023 reported on outcomes for specific subgroups and overall continued to show improvement and reinforced initial findings. The 5 year event-free survival data was 81.3% for those who received the pembrolizumab vs 72.3% for those who received placebo.
For patients with early-stage, high-risk, ER-positive, HER2-negative breast cancer, this phase 3 study found that adding pembrolizumab (Keytruda) to neoadjuvant (before surgery) chemotherapy significantly increased the pathological complete response rate (pCR). This means that at the time of surgery there was less evidence of residual disease for those patients who received pembrolizumab.
This is a pooled analysis of three phase 3 studies looking at the combination of ribociclib (Kisqali) and endocrine therapy for patients with HR–positive/HER2-negative breast cancer. The results presented at SABCS 2023 examined multiple subgroups but found overall that ribociclib and endocrine therapy led to an improvement in progression-free survival and overall survival compared to the placebo plus endocrine therapy. A particularly notable finding was that in patients younger than 65 years there was a median progression-free survival of 31.8 months with the ribociclib combination compared with the placebo group which had a median of 16.4 months of progression-free survival.
A secondary analysis of the POSITIVE trial followed up on findings released last year that determined that young women with early-stage, HR-positive breast cancer could pause endocrine therapy for up to 2 years to become pregnant without increasing their risk for recurrence. Following these findings, the study authors worked to determine whether the use of fertility preservation or assisted reproductive technology had any effect on safety. The study ultimately determined that, for participants who paused endocrine therapy to try to become pregnant, nearly 75% became pregnant after 41 months. Additionally, women who used ovarian stimulation for cryopreservation had a similar likelihood of breast cancer recurrence as those who did not: 9.7% compared to 8.7%.
Results from a phase III trial presented at SABCS2023, which had previously reported an interim analysis, continued to show that adding ribociclib (Kisqali) to an aromatase inhibitor improves invasive disease-free survival for patients with early stage HR+ HER2- breast cancer. Median overall survival rate with this combination now exceeds five years!
An improved RSClin tool was presented that uses more detailed information from a longer follow-up of the TAILORx study. This updated data allows the RSClin tool to personalize the Oncotype DX report results to predict more accurately the 10-year risk of breast cancer recurrence in HR+ HER2- patients who have already completed 5 years of endocrine therapy.
Quality of life updates
Results from the PREFERABLE-EFFECT trial presented at SABCS 2023 found that mBC patients who took part in a nine-month structured exercise program reported reduced side effects and improved quality of life compared to patients that did not partake in the exercise program. The study found that side effects such as fatigue, nausea, pain, and shortness of breath were improved, potentially encouraging compliance with long-term treatments.
Adding capivasertib (Truqap) with fulvestrant (Faslodex) did not have a negative effect on quality of life compared with the placebo plus fulvestrant in patients with aromatase inhibitor–resistant, HR-positive, HER2-negative advanced breast cancer, according to patient-reported outcome results from the phase 3 CAPItello-291 trial. The SABCS 2023 results are encouraging from both an efficacy and safety perspective.
The phase 3 Mammo-50 trial evaluated the US screening recommendations for patients following curative surgery for early breast cancer. The study presented at SABCS 2023 found that patients who reduced screening frequency–to every two years for those who received breast conservation surgery and every three years for those who had mastectomies–had similar outcomes to patients who had annual mammograms. Researchers hope these findings will help lessen the burden of follow-up screenings on patients.
This study offers preliminary insight that a specific type of PET imaging can detect TNBC lesions (that may resist chemotherapy). More investigation must be done, but this development is something to watch given the aggressive nature of TNBC.