FDA Flashback: Breast Cancer Decisions and News From August 2026

Catch a glimpse of the breast cancer–related FDA decisions and announcements from August 2026, including the submission of a supplemental new drug application (sNDA) for a pan-class I PI3K and mTOR inhibitor in PIK3CA-mutant disease and the granting of fast track designation to a first-in-class PARG inhibitor. Additionally, read a preview of anticipated regulatory decisions in estrogen receptor (ER)–positive breast cancer that are expected over the coming months.

What is the significance of the submission of the sNDA to the FDA for gedatolisib (Revtorpyk) in PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer?

On August 26, 2026, an sNDA was submitted to the FDA seeking the approval of gedatolisib in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for the treatment of adult patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer harboring a PIK3CA mutation, following progression on or after treatment with at least 1 line of endocrine therapy.¹ An approval for the combination in this indication would expand gedatolisib’s label beyond its current indication in patients with hormone receptor–positive, HER2-negative disease without a PIK3CA mutation, which the FDA approved in July 2026.

The sNDA was supported by data from the PIK3CA-mutant cohort of the phase 3 VIKTORIA-1 trial (NCT05501886; Study 2), which were presented at the 2026 ASCO Annual Meeting (ASCO 2026).² The trial enrolled 362 patients who were randomly assigned 3:3:1 to receive the gedatolisib triplet of gedatolisib plus fulvestrant and palbociclib (n = 155), alpelisib (Vijoice) plus fulvestrant (n = 155), or the gedatolisib doublet of gedatolisib plus fulvestrant (Arm F; n = 52), following progression on a CDK4/6 inhibitor and a nonsteroidal aromatase inhibitor. At a data cutoff of March 9, 2026, and a median follow-up of 12.8 months (IQR, 7.5-19.9), the gedatolisib triplet produced a median progression-free survival (PFS) by blinded independent central review of 11.1 months (95% CI, 9.0-16.7) compared with 5.6 months (95% CI, 5.2-7.4) for alpelisib plus fulvestrant, representing a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.37-0.68; P < .0001). The safety profile in the PIK3CA-mutant cohort included stomatitis, hyperglycemia, and rash, and was generally consistent with that previously reported in the PIK3CA wild-type cohort.

What is the regulatory status of ETX-19477 in BRCA-mutated, hormone receptor–positive, HER2-negative breast cancer?

On August 18, 2026, the FDA granted fast track designation to ETX-19477, an oral, potent, and selective inhibitor of poly(ADP-ribose) glycohydrolase (PARG), for the treatment of adult patients with BRCA-mutated, hormone receptor–positive, HER2-negative unresectable or metastatic breast cancer.³ ETX-19477 is being evaluated as monotherapy in the ongoing phase 1/2 ERADIC8 trial (NCT06395519), which is enrolling phase 2 cohorts of patients with BRCA-mutated ovarian cancer and BRCA-mutated, hormone receptor–positive, HER2-negative breast cancer. The designation was supported by preclinical findings and clinical data from the study. Initial results from the phase 1 dose-escalation portion presented at ASCO 2026 showed that ETX-19477 monotherapy generated an objective response rate of 57% and a disease control rate of 100% among evaluable phase 2–eligible patients.^3,4

What anticipated FDA approvals might alter the breast cancer treatment paradigm over the next couple of months?

Two regulatory decisions for the oral selective estrogen receptor degrader (SERD) giredestrant are anticipated before the end of 2026.

In the early-stage setting, the FDA granted priority review to an NDA seeking the approval of adjuvant giredestrant for the treatment of adult patients with ER-positive, HER2-negative, stage I to III breast cancer, assigning a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2026.⁵ The NDA is supported by data from the phase 3 lidERA Breast Cancer trial (NCT04961996), which enrolled patients with medium- or high-risk stage I to III disease and showed that adjuvant giredestrant reduced the risk of invasive disease recurrence or death by 30% vs standard-of-care (SOC) endocrine therapy (HR, 0.70; 95% CI, 0.57-0.87; P = .0014). At the 3-year analysis, 92.4% of patients who received giredestrant were alive and free of invasive disease vs 89.6% of those who received SOC endocrine therapy.

In the advanced setting, the FDA accepted for review an NDA seeking the approval of giredestrant in combination with everolimus (Afinitor) for the treatment of patients with ESR1-mutated, ER-positive, HER2-negative locally advanced or metastatic breast cancer following recurrence or progression on a prior endocrine therapy–based regimen; the agency assigned a PDUFA target action date of December 18, 2026.⁶ The NDA was supported by data from the phase 3 evERA Breast Cancer trial (NCT05306340), in which the combination met its coprimary end points of investigator-assessed PFS in the ESR1-mutated and intention-to-treat (ITT) populations. In the ESR1-mutated population, giredestrant plus everolimus produced a median PFS of 9.99 months (95% CI, 8.08-12.94) vs 5.45 months (95% CI, 3.75-5.62) with SOC endocrine therapy plus everolimus, representing a 62% reduction in the risk of disease progression or death (HR, 0.38; 95% CI, 0.27-0.54; P < .0001).⁷ In the ITT population, the median PFS was 8.77 months (95% CI, 6.60-9.59) vs 5.49 months (95% CI, 4.01-5.59), representing a 44% reduction (HR, 0.56; 95% CI, 0.44-0.71; P < .0001).

References

1. Celcuity submits sNDA to FDA for Revtorpyk (gedatolisib) for HR+/HER2-, PIK3CA mutant locally advanced or metastatic breast cancer. News release. Celcuity Inc. August 26, 2026. Accessed September 22, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuity-submits-snda-fda-revtorpyktm-gedatolisib-hrher2-pik3ca
2. Hurvitz SA, Curigliano G, Andre F, et al. A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2-/PIK3CA-mutant advanced breast cancer (VIKTORIA-1 Study 2). J Clin Oncol. 2026;44(suppl 17):LBA1008. doi:10.1200/JCO.2026.44.17_suppl.LBA1008
3. 858 Therapeutics announces FDA fast track designation for PARG inhibitor ETX-19477 for the treatment of patients with BRCA-mutated HR+/HER2- unresectable or metastatic breast cancer. News release. 858 Therapeutics. August 18, 2026. Accessed September 22, 2026. https://www.businesswire.com/news/home/20260818624165/en/858-Therapeutics-Announces-FDA-Fast-Track-Designation-for-PARG-Inhibitor-ETX-19477-for-the-Treatment-of-Patients-with-BRCA-Mutated-HRHER2--Unresectable-or-Metastatic-Breast-Cancer
4. Rosen E, Advani PP, Banda K, et al. First-in-human phase 1/2 study of ETX-19477, an oral, potent, and selective PARG inhibitor in patients with advanced solid tumors (ERADIC8). J Clin Oncol. 2026;44(suppl 16):3109. doi:10.1200/JCO.2026.44.16_suppl.3109
5. FDA accepts new drug application for Roche’s giredestrant in ER-positive early-stage breast cancer, the first and only oral SERD with positive phase III results in the curative setting. News release. Roche. June 2, 2026. Accessed September 22, 2026. https://www.roche.com/media/releases/med-cor-2026-06-02
6. FDA accepts new drug application for Roche’s giredestrant in ESR1-mutated, ER-positive advanced breast cancer. News release. Roche. February 19, 2026. Accessed September 22, 2026. https://www.roche.com/media/releases/med-cor-2026-02-20
7. 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, TX. Abstract GS3-09.