From Abemaciclib to Trastuzumab Deruxtecan: Highlights From the 2024 San Antonio Breast Cancer Symposium

For 47 years, the San Antonio Breast Cancer Symposium (SABCS) has showcased presentations on experimental biology, etiology, prevention, diagnostics, and therapies for patients with breast cancer. Following are some of the notable clinical trial results from the 2024 SABCS meeting.

OlympiA Trial

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Findings from the phase 3 OlympiA trial (NCT02032823) showed that 1 year of treatment with the targeted drug olaparib (Lynparza; AstraZeneca) improved long-term survival in women with high-risk, early-stage breast cancer with BRCA1 or BRCA2 mutations.¹

The first patient was recruited into the OlympiA trial 10 years ago. The findings presented at 2024 SABCS showed that adding olaparib to standard treatment cut the risk of recurrence by 35% and the risk of death by 28%. After 6 years, 87.5% of patients who were treated with olaparib were still alive compared with 83.2% of those who were given placebo.¹

DESTINY-Breast06 Trial

Findings from a new analysis of the phase 3 DESTINY-Breast06 clinical trial (NCT04494425) showed that trastuzumab deruxtecan (T-DXd; Enhertu; Daiichi Sankyo) significantly outperformed chemotherapy in patients with hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer (mBC) who experienced rapid disease progression after prior endocrine-based therapy. The results highlight the potential role of T-DXd as an early-line treatment after 1 or more lines of endocrine-based therapy for patients with hormone receptor–positive, HER2-low/HER2-ultralow mBC.²

Across all subgroups, T-DXd demonstrated improved progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) compared with the physician’s choice of chemotherapy. For patients with the most rapid progression (< 6 months of time to progression [TTP]), the median PFS was 14 months with T-DXd vs 6.5 months with chemotherapy (HR, 0.38; 95% CI, 0.25-0.59). The PFS benefit was also seen in the 6- to 12-month TTP subgroup (13.2 vs 6.9 months; HR, 0.69; 95% CI, 0.43-1.12) and in the TTP beyond 12 months subgroup (12.9 vs 8.2 months; HR, 0.67; 95% CI, 0.51-0.88).²

The ORR also was higher for T-DXd in each subgroup. Among patients with less than 6 months TTP, the ORR was 67.7% for T-DXd compared with 25.4% for the chemotherapy group. For patients who received 6 to 12 months of chemotherapy, the ORR was 60% for T-DXd and 28.8% for chemotherapy. In the TTP beyond 12 months subgroup, the ORR was 59.5% for T-DXd and 33.1% for chemotherapy. DOR similarly favored T-DXd, with a median of 11.1 months for patients with less than 6 months TTP compared with 7.3 months for patients receiving chemotherapy.²

EMBER-3 Trial

Results from the open-label, randomized, phase 3 EMBER-3 trial (NCT06016738) showed that imlunestrant (Eli Lilly and Company), a next-generation selective estrogen receptor degrader, may offer significant protection against disease progression for patients with ESR1-mutated, estrogen receptor–positive, HER2-negative (HER2–) advanced breast cancer (ABC) that has become resistant to standard hormone therapy. The EMBER-3 trial included 874 patients whose disease had recurred or progressed following treatment with an aromatase inhibitor with or without a CDK4/6 inhibitor. No prior therapy for ABC was permitted beyond those treatments.³

Participants were randomly assigned 1:1:1 to receive monotherapy with imlunestrant once daily, a physician’s choice of standard-of-care fulvestrant (Faslodex; AstraZeneca) or exemestane (Aromasin; Pfizer Inc) or a combination of imlunestrant plus abema-ciclib (Verzenio; Eli Lilly and Company). The study’s primary end points included investigator-assessed PFS.³

Among the 256 patients with ESR1 mutations, imlunestrant demonstrated a significant PFS benefit over standard therapy, with a median PFS of 5.5 months compared with 3.8 months (HR, 0.62; 95% CI, 0.46-0.82; P < .001).³ The addition of abemaciclib to imlunestrant yielded a marked PFS improvement across all patients, regardless of ESR1 or PI3K mutation status. The median PFS for the combination group was 9.4 months compared with 5.5 months for imlunestrant alone (HR, 0.57; 95% CI, 0.44-0.73; P < .001).³

PADMA Trial

Palbociclib (Ibrance; Pfizer Inc) plus endocrine therapy (ET) significantly outperforms standard chemotherapy monotherapy as a first-line treatment for women with high-risk, hormone receptor–positive, HER2– mBC who have an indication for chemotherapy. Findings from the phase 4 PADMA clinical trial (NCT03355157) demonstrated that after a median follow-up of 36.8 months, the primary end point of time to treatment failure (TTF) was significantly longer in the palbociclib/ET group than in the chemotherapy group. The median TTF was 17.2 months with palbociclib/ET compared with 6.1 months for chemotherapy (HR, 0.46; 80% CI, 0.35-0.60; P = .0002).⁴

The median PFS was 18.7 months with palbociclib/ET compared with 7.8 months with chemotherapy (HR, 0.45; 95% CI, 0.29-0.70; P = .0002). Time to first subsequent treatment was longer with palbociclib/ET at 19.9 months vs 8 months with chemotherapy (HR, 0.52; 95% CI, 0.34-0.80; P = .0028).⁴

INAVO120 Trial

The combination of inavolisib (GDC-0077; Genentech, Inc), palbociclib, and fulvestrant improved PFS in advanced PIK3CA-mutated, hormone receptor–positive, HER2– breast cancer, according to SABCS presenters of the randomized, double-blind phase 3 INAVO120 trial (NCT04191499). With this trial, investigators introduced a potential new triplet therapy to this patient population.⁵

At a data cutoff date of September 29, 2023, and a median follow-up of 21.3 months, the triplet reduced the risk for progression or death by 57% compared with the doublet (HR, 0.43; 95% CI, 0.32-0.59; P < .0001). Median PFS was 15 months for the triplet compared with 7.3 months for palbociclib and fulvestrant. In addition, the confirmed ORRs were 58.4% and 25%, respectively.⁶

AFT-38 PATINA Trial

The investigators of the open-label phase 3 AFT-38 PATINA trial (NCT02947685) randomly assigned 518 patients 1:1 to 125 mg of oral palbociclib daily plus anti-HER2 therapy of trastuzumab (Herceptin; Genentech, Inc) or trastuzumab plus pertuzumab (Perjeta; Genentech, Inc) every 3 weeks plus ET of letrozole (Femara; Novartis), anastrozole (Arimidex; AstraZeneca), exemestane, or fulvestrant (n = 261) vs the combination without palbociclib (n = 257) until progressive disease or toxicity. Patients had to complete induction chemotherapy and have no evidence of disease progression prior to enrollment.⁷

The confirmed ORR by investigator assessment was 29.9% with palbociclib compared with 22.2% in the control arm (P = .046). Similarly, the clinical benefit rate was also slightly higher with palbociclib at 89.3% vs 81.3%, respectively (P = .01).⁷

A statistically significant and clinically meaningful median PFS improvement was demonstrated with palbociclib plus standard-of-care therapy in patients with hormone receptor–positive, HER2-positive mBC as first-line maintenance therapy. Palbociclib plus anti-HER2 therapy and ET showed median PFS of 44.3 months (95% CI, 32.4-60.9) vs 29.1 months (95% CI, 23.3-38.6) with only anti-HER2 and ET (HR, 0.74; 95% CI, 0.58-0.94; unstratified 1-sided P = .0074). There was a median follow-up of 52.6 months in patients who were disease free.⁷

REFERENCES

1. Major trial shows prolonged benefit of olaparib in early-stage inherited breast cancer. The Institute of Cancer Research. December 12, 2024. Accessed December 12, 2024. https://www.icr.ac.uk/about-us/icr-news/detail/major-trial-shows-prolonged-benefit-of-olaparib-in-early-stage-inherited-breast-cancer

2. Rddad Y. Trastuzumab deruxtecan outperforms chemo in PFS for HER2-low metastatic breast cancer.Oncology News Central. December 13, 2024. Accessed December 15, 2024. https://www.oncologynewscentral.com/breast-cancer/trastuzumab-deruxtecan-outperforms-chemo-in-pfs-for-her2-low-metastatic-breast-cancer

3. Rddad Y. Imlunestrant combo improves PFS in advanced breast cancer. Oncology News Central. December 11, 2024. Accessed December 15, 2024. https://www.oncologynewscentral.com/breast-cancer/imlunestrant-combo-improves-pfs-in-advanced-breast-cancer

4. Rddad Y. Palbociclib plus endocrine therapy beats chemo in HR+/HER2− metastatic breast cancer. Oncology News Central. December 11, 2024. Accessed December 15, 2024. https://www.oncologynewscentral.com/breast-cancer/palbociclib-plus-endocrine-therapy-beats-chemo-in-metastatic-breast-cancer

5. Gerlach A. Ribociclib and inavolisib approvals highlight advances in breast cancer care. Pharmacy Times. December 11, 2024. Accessed December 15, 2024. https://www.pharmacytimes.com/view/fda-approval-of-ribociclib-inavolisib-address-diversity-and-fertility-in-breast-cancer-therapy

6. Tallent A. “I was impressed”: new triplet in PIK3CA-mutated, HR+/HER2-advanced breast cancer. Oncology News Central. December 9, 2023. Accessed December 15, 2024. https://www.oncologynewscentral.com/article/i-was-impressed-new-triplet-in-pik3ca-mutated-hr-her2-advanced-breast-cancer

7. Cohn-Emery D. Palbociclib combo shows benefit to PFS in HR+, HER2+breast cancer. Targeted Oncology. December 12, 2024. Accessed December 15, 2024. https://www.targetedonc.com/view/palbociclib-combo-shows-benefit-to-pfs-in-hr-her2-breast-cancer