Exciting Advances in HR+ Breast Cancer: Top 5 Picks From SABCS

Myles Starr

December 12, 2022

SAN ANTONIO — A wide range of research on hormone receptor (HR)–positive breast cancer was presented last week at the San Antonio Breast Cancer Symposium (SABCS) 2022.

Medscape Medical News spoke with SABCS program director Virginia Kaklamani, MD, leader of the Breast Cancer Program at UT Health, San Antonio, and Jason A. Mouabbi, MD, of the University of Texas MD Anderson Cancer Center, Houston, about their top five picks on HR-positive disease — the research they were most excited about and what the findings could mean for clinical practice and patient outcomes.

1. Addressing an Unmet Need

Data from the phase 3 CAPItello-291 clinical trial, which were presented at general session (GS) 3-04, showed that the addition of the investigational AKT inhibitor capivasertib to fulvestrant resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) among 708 patients with HR-positive, HER2-negative advanced breast cancer compared with those who received placebo plus fulvestrant.

For patients treated with capivasertib plus fulvestrant, median PFS was 7.2 months, compared with 3.6 months for those who received placebo plus fulvestrant (hazard ratio [HR], 0.60). Among patients assigned to the capivasertib group, 41% had tumors with AKT pathway mutations. In this group, the median PFS was 7.3 months, vs 3.1 months in the placebo cohort. The objective response rate among patients with measurable disease was 23% overall in the capivasertib group, compared with 12.2% in the placebo arm; it was 28.8%, vs 9.7%, among the patients with AKT alterations.

Mouabbi noted that the study "met its primary endpoint" and that, importantly, it "addresses an area of unmet need."

"The study's treatment targets the PI3K/AKT/mTOR pathway, which is a very active pathway in hormone-positive metastatic breast cancer," Mouabbi explained. He noted, "We've always wanted to tackle that pathway effectively, and it looks like this drug can do that."

2. Next-Generation SERD

Data from the phase 2 SERENA-2 trial offers evidence that camizestrant, a next-generation selective estrogen receptor degrader (SERD), improved PFS compared with fulvestrant for patients with HR-positive, HER2-negative breast cancer (GS3-02).

Overall, 240 patients were randomly assigned to receive camizestrant monotherapy at various doses or fulvestrant at 500 mg. Among patients who received camizestrant 75 mg, median PFS was 7.2 months; among those who received camizestrant 150 mg, PFS was slightly longer, at 7.7 months, vs 3.7 months for patients treated with fulvestrant. Compared with fulvestrant, camizestrant reduced the risk of disease progression by 42% at 75 mg (HR, 0.58) and by 33% at 150 mg (HR, 0.67). In a subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression by 67% in the group that received 75 mg and by 45% in the group that received 150 mg compared with fulvestrant (median PFS, 6.3, 9.2, and 2.2 months, respectively).

"In this trial, camizestrant looks like a more beneficial treatment in the target group," said Kaklamani. "This is significant because it means that camizestrant could be used in the future in HR-positive metastatic breast cancer instead of fulvestrant." In addition, "camizestrant is taken orally and is much more convenient for patients, unlike fulvestrant, which is taken intramuscularly."

3. Pregnancy Risks

Can endocrine therapy be safely interrupted for women with breast cancer who wish to become pregnant? That's what researchers tried to glean in a recent prospective trial presented at the meeting (GS4-09).

The study enrolled over 500 women for whom endocrine therapy had been stopped in the hopes of their becoming pregnant. Almost all (93.4%) had stage I/II HR-positive breast cancer. The primary objective was to determine the risk of breast cancer relapse associated with interrupting therapy for about 2 years. The authors defined no more than 46 breast cancer–free interval (BCFI) events as the safety threshold. A BCFI event was defined as local, regional, or distant recurrence or a new invasive contralateral breast cancer.

Among 497 women, 368 (74%) had at least one pregnancy and 317 (64%) had at least one live birth, for a total of 365 babies born. At a median follow-up of 41 months, 44 participants experienced a BCFI event, in line with the safety threshold. The 3-year BCFI failure rate was 8.9%, similar to the 9.2% rate in an external control cohort from the SOFT/TEXT trials. In addition, 76.3% of patients resumed endocrine therapy; 15.4% had not yet resumed therapy.

"This trial is more confirmatory but an extremely important step for young women who want to get pregnant after diagnosis and recovery from HR-positive breast cancer," Kaklamani said. "It seems that stopping endocrine therapy to become pregnant did not cause any adverse outcomes or increase the risk of reoccurrence of cancer in the women in the study."

Mouabbi agreed, noting, "Many of our patients are afraid that they will miss the window to get pregnant because they have to be on treatment for so long. This is the first study that let us know pregnancy and safety outcomes in patients who took a break from endocrine therapy to get pregnant. The results are promising and will be exciting for many of our patients."

4. Assay Identifies OFS Benefit

A genomic assay was able to distinguish premenopausal patients with early-stage HR-positive breast cancer who benefited from the addition of ovarian function suppression to adjuvant endocrine therapy, according to new data presented at the meeting (GS1-06).

In the study, investigators analyzed 1717 patient tumor samples from the landmark Suppression of Ovarian Function Trial (SOFT) trial. The Breast Cancer Index identified 58% of women who benefited from the addition of ovarian function suppression to tamoxifen or exemestane therapy. They experienced an absolute benefit of 11.6% (42% did not benefit), compared with those with received tamoxifen alone. The predictive benefit was observed regardless of age, lymph node involvement, and receipt of chemotherapy.

Kaklamani highlighted this study's importance, saying, "Ovarian suppression is associated with severe adverse events for patients. Obviously, the women who will get a benefit should continue, but this research is important because it will hopefully show us who to recommend ovarian suppression to while not exposing patients who are likely to get little benefit to unneeded toxicity."

5. Optimizing Elacestrant PFS

Last year, data from the Emerald trial showed that elacestrant is superior to standard-of-care therapy for HR-positive metastatic breast cancer. An update that Kaklamani presented at SABCS (GS3-01) explored whether the duration of a prior CDK4/6 inhibitor affects PFS.

The study was a randomized, open-label, phase 3 trial in which 478 patients with ER-positive/HER2-negative metastatic breast cancer received either elacestrant or standard of care. These patients had previously received one or two lines of endocrine therapy, a CDK4/6 inhibitor, and ≤1 line of chemotherapy.

Overall, the duration of prior CDK4/6 inhibitor in the metastatic setting was positively associated with PFS — the longer the duration of prior CDK4/6 inhibitor therapy, the longer the PFS with elacestrant. PFS outcomes were even stronger among patients with ESR1 mutations.

"What we found was that the women who benefit most from elacestrant had previously received a CDK4/6 inhibitor for at least 6 months," Kaklamani said. This data can help us determine who may do best on the drug, she added.

San Antonio Breast Cancer Symposium (SABCS) 2022: General sessions 1-06, 3-01, 3-02, 3-04, and 4-09. Presented December 6–9, 2022.

Myles Starr is medical journalist based in New York.

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