New Trials in Breast Cancer: Could Your Patient Benefit?

Helen Leask, PhD

May 16, 2023

Several new clinical trials in breast cancer have opened in recent months. Maybe one of your patients could benefit from enrolling.

Locally advanced unresectable or metastatic HR-positive, HER2-negative, PIK3CA-mutated breast cancer. Adults with this type of breast cancer whose disease has progressed despite treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) are eligible to participate in a randomized, open-label, phase 3 clinical trial comparing two PI3K inhibitors ― the investigational agent inavolisib (from Hoffmann-La Roche) and alpelisib (Piqray). For approximately 5 years or until disease progression or death, participants will take daily tablets of either inavolisib or alpelisib. Everyone will also receive 500 mg of fulvestrant (Faslodex) every 4 weeks. Recruitment for the trial's 400 participants will start in late May 2023 at sites in Oregon and Texas. The primary outcome measure is progression-free survival (PFS). Overall survival (OS) and quality of life (QoL) are secondary measures. More details at

Medscape contributor Kathy Miller, MD, professor of oncology and medicine at the Indiana University School of Medicine, Indianapolis, said that this was the "first direct comparison in the most common second-line group we face ― those who progressed after CDKi therapy."

Stage I–III hormone receptor–positive breast cancer (women only). Women in this situation who report new or worsening musculoskeletal pain while taking aromatase inhibitors (AIs) are being recruited for a randomized, placebo-controlled phase 3 National Cancer Institute (NCI) study to see whether web-based training can improve pain, sleep, and poor adherence to AIs. Over a period of 9 to 10 months, participants in the experimental group will take part in eight interactive online sessions of a pain-coping skills training program and will be encouraged to practice these skills daily. They will also receive usual medical care and an educational booklet about AIs. The control group will receive only usual care and the AI booklet. The study opened in January 2023 at centers in Illinois and North Carolina. Investigators are planning to recruit 452 participants. The primary outcome is change in pain. QoL is a secondary outcome, and OS will not be tracked. More details at

Miller commented that "musculoskeletal pain on aromatase inhibitors is a common reason for nonadherence or early discontinuation. A web-based intervention could reduce barriers to access that limit widespread adoption of other interventions."

Locoregional recurrent or metastatic ER-positive, HER2-negative breast cancer not amenable to surgery or radiation therapyPeople with this type of breast cancer who have received one line of CDK4/6 inhibitors and one or more endocrine treatments for advanced disease can join a randomized, open-label, phase 3 study comparing the investigational agent ARV-471 (from Arvinas and Pfizer) to fulvestrant. Fulvestrant is a selective estrogen–receptor degrader (SERD), while the new drug ARV-471 is a PROTAC estrogen receptor (ER) degrader. It works by directly recruiting the ubiquitin-proteosome system (UPS) by enabling interactions between an E3 ligase (cereblon) and the ER resulting in the destruction of the ER, whereas SERDs indirectly recruit the UPS to eliminate the ER (secondary to conformational changes and/or immobilization of the ER).  

Participants in the experimental group will take oral ARV-471 every day for approximately 2 years or until disease progression or death. Over the same period, individuals in the control group will receive one intramuscular injection of fulvestrant every 28 days. The trial started recruiting 560 participants in March 2023 at sites in California, Florida, New York, Oklahoma, and Texas, as well as five other countries. Centers in Virginia, China, and South Korea are gearing up. The primary outcome measure is PFS. OS and QoL are secondary outcomes. More details at

Miller commented, "More options for endocrine therapy are always welcome."

Early-stage, low-risk HER2-positive breast cancer. Men and women aged 40 or older with this type of breast cancer who have had surgery and are taking HER2-directed therapy may be interested in an NCI-sponsored phase 3 study to see whether such patients still need standard adjuvant radiation therapy. For up to approximately 10 years, all participants will continue to receive standard-of-care HER2 therapy. One group of people will also undergo usual adjuvant breast radiation therapy, while a control group will not. Study centers in 12 states started recruiting 1300 people in March 2023. Time to recurrence (recurrence-free interval) is the primary endpoint. OS over 10.5 years is a secondary endpoint. Apart from patient-reported pain and worry about recurrence, QoL measures will not be tracked. More details at

Miller said, "As systemic therapy becomes more effective, the overall risk of distant and local recurrence goes down; especially in patients with limited disease burden at diagnosis, the risk of local recurrence may be so low that radiation adds little." Miller viewed this trial as "an important next step in asking what treatment component we no longer need to consider a mandate."

Residual invasive triple-negative breast cancer. Individuals in this situation after neoadjuvant therapy and surgery can enroll in a randomized, open-label, phase 3 study testing whether the antibody-drug conjugate sacituzumab govitecan-hzly (Trodelvy) plus pembrolizumab (Keytruda) is more effective than standard of care. Participants in the experimental group will receive weekly intravenous (IV) sacituzumab 2 weeks out of 3 plus IV pembrolizumab every 3 weeks. Individuals in the control group will be given physician's choice of either pembrolizumab alone or a combination of IV pembrolizumab and oral capecitabine. Treatment will continue for approximately 6 months or until disease recurrence, untenable toxicity, trial withdrawal, or death, whichever occurs first., Research sites in 11 states started recruiting 1514 participants in December 2022. The primary endpoint is invasive disease–free survival. OS and QoL are secondary outcomes. More details at

"Patients with residual disease have a high risk of recurrence. There is proven benefit from capecitabine. Can sacituzumab do better?" asked Miller.

Early-stage resected, ER-positive, HER2-negative breast cancer with high/intermediate risk of recurrence. Adults with this type of breast cancer may be eligible for a phase 3 randomized, open-label study comparing camizestrant, an experimental SERD from AstraZeneca, to standard hormone therapy. For up to 5 years, participants will either take camizestrant tablets or continue with investigator's choice of standard endocrine therapy (tamoxifen, anastrozole, letrozole, or exemestane). Cancer centers in New Mexico and Tennessee started recruiting 4300 participants in March 2023; sites in Utah and 10 other countries are gearing up. Invasive breast cancer–free survival is the primary outcome; OS and QoL are secondary outcomes. More details at

Miller commented that this trial gives her "déjà vu," reminding her of the "early move to the adjuvant setting for an oral SERD [and] the early AI switching studies."

All trial information is from the National Institutes of Health US National Library of Medicine (online at Miller is not involved with any of these trials; she writes a regular column on Medscape Oncology ― Miller on Oncology.

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