Clinical trial investigators studying advanced and metastatic breast cancer presented their newest results—largely focused on emerging targeted and immunotherapies—at this year’s San Antonio Breast Cancer Symposium (SABCS).
Read on for highlights from those trial updates, many of which involved BCRF investigators or were supported directly by BCRF.
Dr. Adrienne Waks of the Dana-Farber Cancer Institute presented the first results from the phase 2 AVIATOR clinical trial, funded in part by BCRF (TBCRC 045, NCT03414658). In patients who had previously been treated for HER2-positive metastatic breast cancer (MBC), significant improvement in progression-free survival was observed—3.8 months with the addition of immune checkpoint inhibitor avelumab (Bavencio®) to chemotherapy and trastuzumab (Herceptin®) compared to two months with chemotherapy and trastuzumab alone. Results presented as part of this trial indicate that additional investigation of immune checkpoint blockade in pre-treated HER2-positive metastatic breast cancer is warranted.
This study was chosen for a Rapid-fire Mini-Oral Presentation, a new session at this year’s SABCS that highlights thought-provoking studies in their early stages and allows other researchers to provide guidance on shaping future clinical trials.
HER2CLIMB-02 (NCT03975647) is only the second randomized study after the HER2CLIMB trial led by BCRF investigator Dr. Nancy Lin that includes patients with active or progressing brain metastases. In HER2CLIMB, researchers found that adding tucatinib (Tukysa®) to trastuzumab and capecitabine resulted in better progression-free survival and overall survival in patients with HER2-positive MBC. In the follow-up HER2CLIMB-02 trial, researchers are investigating if the addition of tucatinib to ado-trastuzumab emtansine (T-DM1) results in better outcomes for patients compared to T-DM1 alone.
A primary analysis of this phase 3 trial was presented by Dr. Sara Hurvitz of Fred Hutchinson Cancer Center at the University of Washington, whose research team reported a 24 percent likelihood of reducing disease progression or death by adding tucatinib to T-DM1 in patients previously treated for HER2-positive locally advanced or MBC (9.5 months median time to disease progression or death for combination therapy versus 7.4 months with T-DM1 alone). For those patients with brain metastasis (40 percent of trial participants), a 36 percent reduction in disease progression or death was observed in the combined therapy (7.8 months median time to disease progression or death versus 5.7 months with T-DM1 alone). These results further support the use of the highly selective tyrosine kinase inhibitor tucatinib in patients with HER2-positive locally advanced or MBC.
BCRF investigator Dr. Luca Gianni presented an update to the phase 3 APTneo trial (NCT03595592) in a late-breaking abstracts oral session. The study tested the role of adding the immune checkpoint inhibitor atezolizumab (Tecentriq®) to targeted HER2 treatments and chemotherapy with and without anthracyclines in HER2-positive, early high-risk, and locally advanced breast cancer.
While the study investigators found that the addition of atezolizumab to targeted treatments and chemotherapy did not statistically increase pathologic complete response rates (pCR), adding atezolizumab to anthracyclines followed by the targeted treatments and chemotherapy did increase pCR by a statistically significant 9.9 percent compared to patients who only received targeted treatments and chemotherapy.
Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center presented the primary analysis of the phase 1 INAVO120 trial (NCT04191499). INAVO120 compared inavolisib, a highly potent and selective inhibitor of the tumor marker PI3KC⍺, plus CDK 4/6 inhibitor palbociclib (Ibrance®) and fulvestrant to palbociclib and fulvestrant alone in patients with PIK3C⍺-mutated hormone receptor (HR)–positive, HER2-negative advanced breast cancer.
This drug combination may represent a new standard of care for patients with the PI3KC⍺ mutation facing resistance to palbociclib and fulvestrant. The addition of inavolisib demonstrated a significant improvement in progression-free survival within 12 months of adjuvant endocrine therapy. Median progression-free survival was 15 months with inavolisib versus 7.3 months with palbociclib and fulvestrant alone.
The efficacy of the newly-FDA approved capivasertib (Truqap™) was evaluated in the trial CAPItello-291 (NCT04305496) and an update on patient-reported outcomes was presented by BCRF investigator Dr. Mafalda Oliveira in a poster spotlight session at this year’s meeting. Dr. Oliveira presented significantly improved progression-free survival in patients treated with capivasertib and fulvestrant as well as a manageable safety profile of the drug combination.
Patients reported no statistically significant change in functional or symptom scores in the capivasertib plus fulvestrant group with the exception of diarrhea. These data further support a positive risk-benefit profile for capivasertib and highlight the importance of assessing quality of life in new treatments for advanced breast cancer.
Dr. Michail Ignatiadis of Institut Jules Bordet presented findings from the phase 3 ALEXANDRA/IMpassion030 trial (NCT03498716). The study investigates the value of adding immune checkpoint inhibitor atezolizumab to standard anthracycline and taxane-based adjuvant chemotherapy in TNBC. The conclusions of their interim analysis do not support the addition of atezolizumab to the chemotherapy regimen in patients who have undergone primary surgery for early TNBC.
The knowledge gained from this research, despite the negative results, helps the research community design future studies and define the most appropriate settings for treatments. In this case, immunotherapies such as atezolizumab may work better in the neoadjuvant setting when more tumor is present.
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