FDA Flashback: Breast Cancer Decisions and News From February 2026

Catch a glimpse of the breast cancer–related FDA decisions granted in February 2026, including imminent decisions to watch, earlier pipeline developments to keep an eye on, and Risk Evaluation and Mitigation Strategy (REMS) updates.

What does the regulatory timeline look like for datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) in metastatic triple-negative breast cancer (TNBC)?

On February 3, 2026, the FDA announced the granting of priority review to a supplemental biologics license application (sBLA) seeking the approval of frontline Dato-DXd for the treatment of adult patients with unresectable or metastatic TNBC who are ineligible for PD-1– or PD-L1–directed immunotherapy.¹ This sBLA submission was backed by findings from the phase 3 TROPION-Breast02 trial (NCT05374512), in which patients who received Dato-DXd (n = 323) experienced a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.64-0.98; P = .0291) and a 43% reduction in the risk of disease progression or death (HR, 0.57; 95% CI, 0.47-0.69; P < .0001) vs those who received investigator’s choice of chemotherapy (n = 321).^1,2 The median overall survival was 23.7 months (95% CI, 19.8-25.6) in the Dato-DXd arm vs 18.7 months (95% CI, 16.0-21.8) in the chemotherapy arm. The median progression-free survival (PFS) values by blinded independent central review in these respective arms were 10.8 months (95% CI, 8.6-13.0) and 5.6 months (95% CI, 5.0-7.0).

Notably, the Prescription Drug User Fee Act (PDUFA) target action date for the sBLA is in the second quarter of 2026.¹

Will giredestrant (GDC-9545) plus everolimus (Afinitor) be FDA approved for ESR1-mutated, estrogen receptor (ER)–positive advanced breast cancer?

On February 20, 2026, the FDA accepted for review a new drug application (NDA) seeking the approval of giredestrant plus everolimus for the treatment of patients with ESR1-mutated, ER-positive, HER2-negative locally advanced or metastatic breast cancer who have disease recurrence or progression on a prior endocrine therapy–based regimen.³ The NDA was backed by data from the phase 3 evERA Breast Cancer trial (NCT05306340), in which the combination of giredestrant and everolimus (n = 102) elicited a median PFS of 9.99 months (95% CI, 8.08-12.94) compared with 5.45 months (95% CI, 3.75-5.62) with standard-of-care (SOC) endocrine therapy plus everolimus (n = 105) among patients with ESR1-mutated disease (HR, 0.38; 95% CI, 0.27-0.54; P < .0001).^3,4

The PDUFA target action date for this decision is December 18, 2026.³

“At the 2025 San Antonio Breast Cancer Symposium, we presented data from evERA Breast Cancer looking at important subgroups, showing that not only, as we showed previously at the 2025 ESMO Congress, giredestrant has consistent benefit across all key clinical pathologic subgroups, but it also has benefit regardless of PI3K status,” Erica L. Mayer, MD, MPH, said in an interview with OncLive^®. Mayer is director of Breast Cancer research at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts. “Patients with co-mutations in ESR1 and PIK3CA derive substantial benefit from the use of giredestrant plus everolimus. This [benefit] is also independent of prior duration on CDK4/6 inhibitors. Patients who had perhaps a shorter duration on CDK4/6 inhibitors are still getting benefit from giredestrant plus everolimus, as are those with longer durations. These are exciting data, and we hope this combination of an oral selective estrogen receptor degrader and a targeted partner may become a new SOC for a broad group of patients post-CDK4/6 inhibition.”

What is the regulatory status of polymerase DNA theta inhibition in BRCA-mutated, HER2-negative breast cancer?

On February 23, 2026, the FDA granted fast track designation to the combination of the polymerase theta inhibitor ART6043 and the PARP inhibitor olaparib (Lynparza) for the treatment of adult patients with germline BRCA-mutated, HER2-negative, locally advanced or metastatic breast cancer who have not received prior therapy with a PARP inhibitor.⁵ This designation was based on findings from an ongoing, first-in-human phase 1/2a trial (NCT05898399) investigating the combination in patients with advanced solid tumors harboring DNA damage response pathway mutations, including patients with germline BRCA-mutated, HER2-negative breast cancer. Among patients in the total population who received ART6043 plus olaparib (n = 42), grade 3 or higher treatment-related adverse effects occurred in 23.8%, the most common being anemia (11.9%) and nausea (4.8%).⁶ Of the 4 patients with breast cancer treated in the study, 3 were ongoing treatment at the time of data presentation, and 2 were expected to benefit with the combination.

What breast cancer regimen received breakthrough therapy designation from the FDA in February 2026?

On February 3, 2026, the FDA granted breakthrough therapy designation to zovegalisib (RLY-2608) plus fulvestrant (Faslodex) for the treatment of adult patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer following disease progression or recurrence on or after treatment with a CDK4/6 inhibitor.⁷ This decision was backed by findings from the phase 1/2 ReDiscover trial (NCT05216432), in which the combination elicited a median PFS of 11.0 months (95% CI, 7.3-22.0) among patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who were treated in the second-line setting with zovegalisib at the recommended phase 3 dose of 600 mg twice daily administered in the fasted state, plus fulvestrant (n = 64).^7,8

What updated FDA REMS news is important to note?

In February, the FDA issued safety updates under the REMS program for the biosimilars denosumab-qbde (Enoby) and denosumab-dssb (Ospomyv), which both reference denosumab (Prolia).^9,10 The updates for each of these biosimilars emphasize the increased risk for severe hypocalcemia following treatment in patients with advanced chronic kidney disease, including those who are dependent on dialysis. Notably, Enoby and Ospomyv are both indicated for use in all indications of reference denosumab, which include increasing bone mass in women receiving adjuvant aromatase inhibitors for the treatment of breast cancer who are at high risk for fracture.^11,12

That’s a wrap!

Want more news? Check out our breast cancer page for the latest updates and expert insights across the field. We’ve got HER2-positive breast cancer treatment developments covered, too!

References

1. Datroway (datopotamab deruxtecan-dlnk) granted priority review in the US as 1st-line treatment for patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. News release. AstraZeneca. February 3, 2026. Accessed March 3, 2026. https://www.astrazeneca-us.com/media/press-releases/2026/DATROWAY-datopotamab-deruxtecan-dlnk-granted-Priority-Review-in-the-US-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-candidates-for-immunotherapy.html
2. Dent RA, Shao Z, Schmid P, et al. First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: primary results from the randomised, phase 3 TROPION-Breast02 trial. Ann Oncol. 2025;36(suppl 2):S1566-S1567. doi:10.1016/j.annonc.2025.09.031
3. FDA accepts new drug application for Roche’s giredestrant in ESR1-mutated, ER-positive advanced breast cancer. News release. Roche. February 19, 2026. Accessed March 3, 2026. https://www.roche.com/media/releases/med-cor-2026-02-20
4. Rugo HS, Tolaney SM, Jhaveri KL, et al. Clinical and biomarker subgroup analysis of evERA Breast Cancer: a phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, Texas. Abstract GS3-09.
5. Artios Receives U.S. FDA fast track designation for DNA polymerase theta (Polθ) inhibitor ART6043 for treatment of gBRCA-mutated HER2-negative breast cancer. News release. Artios Pharma Limited. February 23, 2026. Accessed March 3, 2026. https://www.artios.com/press-release/artios-receives-u-s-fda-fast-track-designation-for-dna-polymerase-theta-pol%CE%B8-inhibitor-art6043-for-treatment-of-gbrca-mutated-her2-negative-breast-cancer/
6. Yap TA, Lakhani N, Barve M, et al. 924MO First data disclosure of the first-in-class DNA polymerase theta inhibitor, ART6043, as monotherapy and in combination with olaparib, in patients with molecularly-selected advanced solid tumors. Ann Oncol. 2025;36(suppl 2):S566-S567. doi:10.1016/j.annonc.2025.08.1493
7. Relay Therapeutics announces zovegalisib granted breakthrough therapy designation by U.S. FDA for PIK3CA-mutant, HR+/HER2- advanced breast cancer. News Release. Relay Therapeutics, Inc. February 3, 2026. Accessed March 3, 2026. https://ir.relaytx.com/news-releases/news-release-details/relay-therapeutics-announces-zovegalisib-granted-breakthrough
8. Sammons SL, Manich CS, Italiano A, et al. Updated efficacy of mutant-selective PI3Kα inhibitor RLY-2608 in combination with fulvestrant in patients with PIK3CA-mutant HR+HER2- advanced breast cancer: ReDiscover trial. J Clin Oncol. 2025;43(suppl 16):1086. doi:10.1200/JCO.2025.43.16_suppl.1086
9. Enoby REMS FDA required REMS safety information. News release. Hikma Pharmaceuticals USA Inc. January 2026. Accessed March 3, 2026. https://syneoshealth4.my.salesforce.com/sfc/p/#5f000001BTYC/a/Ka0000015lsX/3GldqJ6UgqU44rYrvig5Pv5uOSHq.ZiOdOAy7aFO0pU
10. FDA-required REMS safety information / important safety notice. Samsung Bioepis Co., Ltd. Accessed March 3, 2026. https://syneoshealth4--ospomyvdev.sandbox.my.salesforce.com/sfc/p/#Dg0000001rel/a/Dg0000004vVM/D11SKkbu3lf8x8M2aiKEKjAMqn_b64mEsDVBLiN64Y4
11. Enoby. Prescribing information. FDA. September 2025. Accessed March 3, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761439s000lbl.pdf
12. FDA approves Samsung Bioepis’ Ospomyv, Xbryk (denosumab-dssb), a biosimilar to Prolia and Xgeva. News release. Samsung Bioepis Co., Ltd. February 16, 2025. Accessed March 3, 2026. https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=435&currentPage=1