FDA Flashback: Breast Cancer Decisions and News From May 2026

Catch a glimpse of the breast cancer–related FDA decisions granted in May 2026, including several drug approvals and an updated Prescription Drug User Fee Act (PDUFA) target action date.

What is notable about the FDA approval of vepdegestrant (Veppanu) for estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced breast cancer?

On May 1, 2026, the FDA approved vepdegestrant for the treatment of adult patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-approved test, who have disease progression after 1 or more lines of endocrine therapy.¹

This regulatory decision was supported by findings from the phase 3 VERITAC-2 trial (NCT05654623). In the trial, patients with disease harboring ESR1 mutations who received vepdegestrant (n = 136) achieved a median progression-free survival (PFS) of 5.0 months (95% CI, 3.7-7.4) vs 2.1 months (95% CI, 1.9-3.5) among those who received fulvestrant (Faslodex; n = 134; HR 0.57; 95% CI, 0.42-0.77; P = 0.0001).^1,2 The respective overall response rates in these arms were 19% (95% CI, 12%-27%) vs 4% (95% CI, 1.6%-10%).

“The approval…is currently based on [status of] ESR1 mutations, which are activating mutations in the ER that develop as a resistance mutation to aromatase inhibitors,” Kelly E. McCann, MD, PhD, of the University of California San Diego, said in an interview with OncLive^®. “The most important thing going forward is going to be the combination therapy trials. Those clinical trials are important because hopefully at some point, we’ll be able to replace fulvestrant with these oral therapies that are well tolerated per patient preference.”

Watch McCann’s full commentary on the approval here:

Is there a companion diagnostic for vepdegestrant use in breast cancer?

On May 4, 2026, the FDA approved the Guardant360 CDx liquid biopsy as a companion diagnostic for vepdegestrant use in the treatment of patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer.³ Guardant360 CDx is a blood-based, non-invasive assay that is used to identify ESR1 mutations, the presence of which is required for vepdegestrant use.

What is the regulatory status of RPTR-1-201 in breast cancer?

On May 7, 2026, the FDA granted fast track designation to the T-cell receptor bispecific antibody RPTR-1-201 for the treatment of adult patients with HLA-A*02:01–positive unresectable or metastatic triple-negative breast cancer (TNBC) who have progressed on or are intolerant to available standard therapies.⁴ This agent is currently under evaluation as monotherapy and in combination with PD-1 inhibitors in patients with advanced solid tumors in the phase 1/2 RaPTR-101 trial (NCT07293754). The first patient was dosed as of April 23, 2026.⁵

What is important to note about the most recent indications for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in early-stage HER2-positive breast cancer?

On May 15, 2026, the FDA approved neoadjuvant T-DXd for the treatment of adult patients with HER2-positive stage II or III breast cancer, as determined by an FDA-authorized test, followed by a taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP).⁶ The regulatory agency simultaneously granted approval to T-DXd for the treatment of adult patients with HER2-positive breast cancer and residual invasive disease following neoadjuvant HER2-directed therapy.

The neoadjuvant indication was supported by findings from the phase 3 DESTINY-Breast11 trial (NCT05113251), in which patients who received T-DXd followed by THP (n = 321) experienced a pathological complete response (pCR) rate of 67.3% (95% CI, 61.9%-72.4%) vs 56.3% (95% CI, 50.6%-61.8%) in those who received doxorubicin and cyclophosphamide followed by THP (n = 320; P = .003). The post-neoadjuvant indication was supported by findings from the phase 3 DESTINY-Breast05 trial (NCT04622319), in which T-DXd (n = 818) generated a 3-year invasive disease-free survival rate of 92.4% (95% CI, 89.7%-94.4%) compared with 83.7% (95% CI, 80.2%-86.7%) with ado-trastuzumab emtansine (Kadcyla; T-DM1; n = 817; HR, 0.47; 95% CI, 0.34-0.66; P < .0001).

“DESTINY-Breast05 represents the culmination of years of work,” Charles E. Geyer, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania, said in an interview with OncLive. “We’ve always had that recognition that maybe non-pCR patients need better therapy and more therapy, but we didn’t have novel drugs with new mechanisms of actions until we had the antibody-drug conjugates. They made a huge difference, and we took a big step with T-DM1 and another big step with T-DXd. Now, T-DXd has pretty much replaced T-DM1 in this setting. The FDA could have said, ‘[T-DXd is] only approved in the patients [we] included [in the trial], and the patients [we] didn’t include should still get T-DM1.’ However, they didn’t; they left that to the discretion of the physicians with this approval. The neoadjuvant approval was a bit of a surprise, but it has some advantages. It is going to cause some confusion, though, as to what we do.”

What are the highlights of the FDA approval of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for unresectable/metastatic TNBC?

On May 22, 2026, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic TNBC who are not eligible to receive PD-1/PD-L1–directed treatment. This regulatory decision was supported by data from the phase 3 TROPION-Breast02 trial (NCT05374512).⁷ In the trial, treatment with Dato-DXd generated a statistically significant and clinically meaningful improvement in overall survival (OS) vs investigator’s choice of chemotherapy in patients with metastatic TNBC who were not candidates for PD-1/PD-L1 inhibitor therapy (HR, 0.79; 95% CI, 0.64-0.98; P = .0290).

“If a patient recurs 1 year or 9 months after [prior lines of chemotherapy and immunotherapy], we’re not going to be inclined to give them the same chemotherapy or similar chemotherapy again,” Rena D. Callahan, MD, of the David Geffen School of Medicine at UCLA in Los Angeles, California, said in an interview with OncLive. “We want a different option, and Dato-DXd presents us with that option.”

Watch Callahan’s full commentary on the approval here:

What is the regulatory status of camizestrant in hormone receptor–positive advanced breast cancer with an emergent ESR1 mutation?

On May 27, 2026, the FDA announced the extension of the PDUFA target action date for review of the new drug application (NDA) seeking the approval of first-line camizestrant in combination with a CDK4/6 inhibitor for the treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutation.⁸ The NDA is backed by data from the phase 3 SERENA-6 trial (NCT04964934). Data presented at the 2025 ASCO Annual Meeting demonstrated that among patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors had an emergent ESR1 mutation, switching to camizestrant in combination with a CDK4/6 inhibitor (n = 157) yielded a median PFS of 16.0 months (95% CI, 12.7-18.2) per investigator assessment compared with 9.2 months (95% CI, 7.2-9.5) in patients who continued treatment with an aromatase inhibitor plus a CDK4/6 inhibitor (n = 158; HR, 0.44; 95% CI, 0.31-0.60; P < .00001).⁹ Updated findings shared at the 2025 San Antonio Breast Cancer Symposium showed that the median PFS was 16.6 months (95% CI, 14.7-19.4) in the camizestrant arm compared with 9.2 months (95% CI, 7.2-9.7) in the control arm (HR, 0.46; 95% CI, 0.34-0.62; P < .00001).¹⁰

Following these data readouts, on April 30, 2026, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 6-3 against the clinically meaningful benefit of switching to camizestrant in combination with a CDK4/6 inhibitor after detecting an ESR1 mutation in circulating tumor DNA (ctDNA) before radiographic progression.¹¹

Looking for additional commentary on the ODAC decision? Pedram Razavi, MD, PhD, and Dara S. Ross, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, discussed the news as part of an OncLive On Air^® podcast episode about the evolution of ESR1 mutation–directed breast cancer management.¹²

Most recently, additional data from the trial were presented at the 2026 ASCO Annual Meeting.¹³ Notably, the trial met its time to second progression (PFS2) end point, with the switch to camizestrant eliciting a median PFS2 of 25.7 months (95% CI, 20.4-30.3) vs 19.1 months (95% CI, 16.8-21.0) with continuation of an aromatase inhibitor in combination with a CDK4/6 inhibitor (n = 158; HR, 0.63; 95% CI, 0.46-0.86; P = .00373). Additionally, the exploratory ctDNA analysis showed that the rate of total ctDNA clearance was higher among evaluable patients in the camizestrant arm (n = 98), at 51.0% compared with 1.9% among evaluable patients in the control arm (n = 108). ctDNA clearance was also associated with an OS benefit when data were pooled across arms (HR, 0.39; 95% CI, 0.19-0.73).

“If [the FDA does] approve it, [this will] end up changing the paradigm of what we do for patients,” Jane L. Meisel, MD, FASCO, of the Emory University School of Medicine in Atlanta, Georgia, said in an interview with OncLive. “It would mean we should be presumably checking for ESR1 [mutations] on many of these patients at baseline as they start their treatment for metastatic disease, and then potentially making a switch based on these molecular markers, as opposed to imaging, if [imaging is] saying [the patient is] not ready [for a switch in therapy]. That changes things, and we don’t yet have that option.”

References

1. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. FDA. May 1, 2026. Accessed June 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast
2. Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. J Clin Oncol. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000
3. Guardant Health receives FDA approval for Guardant360 CDx as a companion diagnostic for Arvinas and Pfizer’s Veppanu (vepdegestrant) for patients with ER+/HER2- advanced breast cancer with ESR1 mutations. News release. Guardant Health. May 4, 2026. Accessed June 9, 2026. https://investors.guardanthealth.com/press-releases/press-releases/2026/Guardant-Health-Receives-FDA-Approval-for-Guardant360-CDx-as-a-Companion-Diagnostic-for-Arvinas-and-Pfizers-VEPPANU-vepdegestrant-for-Patients-with-ERHER2--Advanced-Breast-Cancer-with-ESR1-Mutations/default.aspx
4. Repertoire Immune Medicines announces FDA fast track designation for its investigational immune medicine, RPTR-1-201. News release. Repertoire. May 7, 2026. Accessed June 9, 2026. https://www.repertoire.com/about/press-releases/repertoire-immune-medicines-announces-fda-fast-track-designation-for-its-investigational-immune-medicine-rptr-1-201
5. Repertoire Immune Medicines announces first participant dosed in phase 1/2 trial of RPTR-1-201, a T cell-targeted immune medicine for advanced solid tumors. News release. Repertoire. April 23, 2026. Accessed June 9, 2026. https://www.repertoire.com/about/press-releases/repertoire-immune-medicines-announces-first-participant-dosed-in-phase-1-2-trial-of-rptr-1-201-a-t-cell-targeted-immune-medicine-for-advanced-solid-tumors
6. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. FDA. May 15, 2026. Accessed June 9, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage
7. Datroway approved in the U.S. as first TROP2 directed antibody drug conjugate for first-line treatment of patients with metastatic triple negative breast cancer who are not PD-1/PD-L1 inhibitor candidates. News release. Daiichi Sankyo. May 22, 2026. Accessed June 9, 2026. https://daiichisankyo.us/web/dsi/press-releases/-/article/datroway-approved-in-the-us-as-first-trop2-directed-antibody-drug-conjugate-for-first-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-pd-1pd-l1-inhibitor-candidates
8. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed June 9, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html
9. Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4
10. Bidard FC, Mayer EL, Park YH, et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA dynamics from SERENA-6, a phase 3 trial of camizestrant + CDK4/6 inhibitor for emergent ESR1m during first-line endocrine-based therapy and ahead of disease progression in patients with HR+/HER2– advanced breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF7-03.
11. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed June 9, 2026. https://www.youtube.com/live/taCx7enN7hk
12. Razavi P, Ross DS. Evolving ESR1 mutation testing directions complicate the future of metastatic breast cancer management: with Pedram Razavi, MD, PhD; and Dara S. Ross, MD. OncLive.com. May 20, 2026. Accessed June 9, 2026. https://www.onclive.com/view/evolving-esr1-mutation-testing-directions-complicate-the-future-of-metastatic-breast-cancer-management-with-pedram-razavi-md-phd-and-dara-s-ross-md
13. Bidard F-C, Mayer E, Park YH, et al. First-line camizestrant for emergent ESR1mutations in advanced breast cancer: final progression-free survival results 2 from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 17):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007