Research Rewind: Phase 3 Breast Cancer Data Highlights From Q2 2026

Recent months have been filled with breast cancer research highlights from major conferences and more. Need a refresher? We’ve got you covered with this recap of pivotal phase 3 data announcements and highlights, many of which have already changed the breast cancer treatment paradigm across disease subtypes.

What updated data from DESTINY-Breast11 are important to note?

The neoadjuvant use of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) reduced the extent of residual cancer burden (RCB) vs dose-dense doxorubicin and cyclophosphamide followed by THP in patients with high-risk, HER2-positive early-stage breast cancer.¹ Data from an analysis of the phase 3 DESTINY-Breast11 trial (NCT05113251) presented at the 2026 ESMO Breast Cancer Congress showed a combined rate of RCB-0 and RCB-I of 81.3% with the T-DXd–based combination (n = 321) vs 69.1% with the comparator regimen (n = 320). Investigators saw RCB-0/RCB-I rate improvements across all prespecified patient subgroups. Additionally, the respective RCB-0 rates were 68.8% and 57.5%.

Notably, in May 2026, earlier data from DESTINY-Breast11 supported the FDA approval of neoadjuvant T-DXd followed by THP for the treatment of adult patients with HER2-positive stage II or III breast cancer, as determined by an FDA-authorized test.²

“[The RCB analysis] indicates that T-DXd/THP benefited even patients who have not achieved a pCR, and this pattern of RCB shift in previous trials was strongly associated with subsequent improvements in recurrence-free survival,” lead study author Lajos Pusztai, MD, DPhil, of the Yale School of Medicine in New Haven, Connecticut, told OncLive^®.

What were the findings from the final analysis of CAPItello-291?

Although the addition of capivasertib (Truqap) to fulvestrant (Faslodex) generated a numerical trend toward improved overall survival (OS) vs placebo plus fulvestrant in patients with PIK3CA/AKT1/PTEN–altered, hormone receptor–positive, HER2-negative advanced breast cancer, the trial was underpowered to show a statistically significant difference on OS in this subgroup, according to the final data readout of the phase 3 CAPItello-291 trial (NCT04305496) presented at ESMO Breast 2026.³ Among patients with PIK3CA/AKT1/PTEN–altered disease (n = 289), the median OS was 28.5 months with capivasertib plus fulvestrant vs 30.4 months with placebo plus fulvestrant (HR, 0.83; 95% CI, 0.63-1.10; P = .201). In the overall population (n = 708), the investigators saw no meaningful numerical difference in the risk of death, with respective median OS values of 29.4 months and 28.6 months (HR, 1.00; 95% CI, 0.83-1.19).

How has giredestrant performed across subgroups of patients with ER-positive, HER2-negative early breast cancer?

Adjuvant giredestrant produced a benefit in invasive disease-free survival (iDFS) vs standard-of-care (SOC) endocrine therapy in both premenopausal and postmenopausal patients with estrogen receptor (ER)–positive, HER2-negative early breast cancer.⁴ Findings from a prespecified subgroup analysis of the phase 3 lidERA Breast Cancer trial (NCT04961996), which were presented at the 2026 ASCO Annual Meeting, showed that giredestrant reduced the risk of invasive disease or death by 35% in the premenopausal patients (n = 1687) vs SOC endocrine therapy (HR, 0.65; 95% CI, 0.44-0.95). The respective 3-year iDFS rates were 94.0% and 91.5%. Among the postmenopausal patients (n = 2456), adjuvant giredestrant also reduced the risk of invasive disease or death vs SOC endocrine therapy (HR, 0.74; 95% CI, 0.57-0.96), with 3-year iDFS rates of 91.3% vs 88.3%, respectively.

Notably, in June 2026, the FDA granted priority review to a new drug application (NDA) seeking the approval of adjuvant giredestrant for the treatment of adult patients with ER-positive, HER2-negative, stage I to III breast cancer.⁵ The NDA was based on data from lidERA Breast Cancer. The Prescription Drug User Fee Act target action date is November 30, 2026.

How has giredestrant plus everolimus performed in post-progression ER-positive, HER2-negative advanced breast cancer?

The combination of giredestrant and everolimus (Afinitor) improved progression-free survival after next of line therapy (PFS2) and prolonged chemotherapy-free survival vs SOC endocrine therapy plus everolimus in patients with ER-positive, HER2-negative advanced breast cancer who had previously received a CDK4/6 inhibitor.⁶Exploratory post-progression analyses from the phase 3 evERA BC trial (NCT05306340) presented at ASCO 2026 demonstrated that in the overall study population, the median PFS2 was 19.02 months (95% CI, 15.51-not estimable) with giredestrant/everolimus (n = 183) compared with 13.17 months (95% CI, 11.70-15.57) with SOC endocrine therapy/everolimus (n = 190; HR, 0.69; 95% CI, 0.51-0.92). Additionally, the median chemotherapy-free survival was 11.10 months (95% CI, 9.50-12.59) in the giredestrant arm vs 7.89 months (95% CI, 6.53-9.49) in the SOC arm (HR, 0.61; 95% CI, 0.47-0.79).

What were the efficacy outcomes with giredestrant plus palbociclib in ER-positive, HER2-negative locally advanced or metastatic breast cancer?

Giredestrant plus palbociclib (Ibrance) did not elicit a statistically significant improvement in investigator-assessed progression-free survival (PFS) compared with letrozole plus palbociclib in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer.⁷ Findings from the primary analysis of the phase 3 persevERA BC trial (NCT04546009) presented at ASCO 2026 showed a median investigator-assessed PFS of 33.1 months (95% CI, 30.2-38.2) among patients who received giredestrant (n = 495) compared with 28.2 months (95% CI, 25.0-33.1) among those who received letrozole (n = 497; HR, 0.89; 95% CI, 0.76-1.05; P = .1553). The respective 12-, 24-, and 36-month PFS rates in the giredestrant arm were 77.8%, 59.7%, and 45.8%. These rates in the letrozole arm were 77.3%, 57.3%, and 41.9%, respectively.

What new data support potential chemotherapy de-escalation for high-risk, ER-positive, HER2-negative early breast cancer?

Prosigna assay–directed adjuvant treatment was shown to be noninferior to standard chemotherapy followed by endocrine therapy for invasive breast cancer–free survival (IBCFS) in patients with high clinical risk, ER-positive/HER2-negative early breast cancer.⁸

First results from the phase 3 OPTIMA trial (ISRCTN42400492) presented at ASCO 2026 showed that in the per-protocol population, the 5-year IBCFS rate was 90.3% (95% CI, 88.5%-91.8%) in the test-directed arm (n = 2094) compared with 91.8% (95% CI, 90.1%-93.2%) in the control arm (n = 2059), translating to a 1.5% absolute difference favoring chemotherapy and meeting the trial’s prespecified 3% noninferiority margin (adjusted HR, 1.03; 90% CI, 0.85-1.25; P = .006).

“We divided our patients into subgroups, and this is where [data] get particularly interesting,” Robert Stein, MBBS, PhD, of UCL Cancer Institute in London, United Kingdom, stated in an interview with OncLive. “We treated everybody, all premenopausal women, [including those who underwent] ovarian function suppression for 3 years or more, and unlike any of the previous trials, we showed no difference in recurrence risks between the 2 trial arms.”

See more of Stein’s commentary below:

What is notable about the final KEYNOTE-522 data readout?

Data from the final analysis of the phase 3 KEYNOTE-522 trial (NCT03036488) presented at ASCO 2026 showed that at a median follow-up of 93.8 months (range, 84.7-102.8), neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by definitive surgery and adjuvant pembrolizumab (n = 784) generated a 7-year event-free survival (EFS) rate of 78.3% (95% CI, 75.3%-81.1%) compared with 69.8% (95% CI, 65.0%-74.2%) with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo (n = 390; HR, 0.68; 95% CI, 0.54-0.86).⁹ The 7-year OS rates were 85.1% (95% CI, 82.5%-87.5%) vs 77.2% (95% CI, 72.7%-81.1%), respectively (HR, 0.64; 95% CI, 0.49-0.85).

“Sometimes when we continue follow-up, the impressive results we observed in the beginning start to decrease; after 7 or 8 years, the benefit is [often] much lower,” Javier Cortés, MD, of the International Breast Cancer Center in Spain, said in an interview with OncLive. “[In KEYNOTE-522], the good news is that the benefit is not worse; it is even numerically better. We have seen clearly and consistently that adding pembrolizumab improves pathological response, EFS, improves distant disease–free survival, and OS.”

What were the PFS2 outcomes from SERENA-6?

The switch to camizestrant plus a CDK4/6 inhibitor upon the emergence of an ESR1 mutation detection in circulating tumor DNA (ctDNA) before radiographic disease progression extended PFS2 vs continued treatment with an aromatase inhibitor plus a CDK4/6 inhibitor in patients with ER-positive, HER2-negative advanced breast cancer.¹⁰

Final PFS2 data from the phase 3 SERENA-6 trial(NCT04964934) presented at ASCO 2026 demonstrated that patients in the camizestrant arm (n = 157) achieved a median PFS2 of 25.7 months (95% CI, 20.4-30.3) vs 19.1 months (95% CI, 16.8-21.0) for those in the control arm (n = 158; HR, 0.63; 95% CI, 0.46-0.86; P = .00373). The respective 30-month PFS2 rates were 41.5% vs 29.7%.

What exploratory analysis data have been seen with sacituzumab govitecan in TNBC?

Findings from an exploratory post hoc analysis of the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) presented at ASCO 2026 showed that at a median follow-up of 14.0 months (range, 0.1-28.6), patients with previously untreated, locally advanced unresectable or metastatic PD-L1–positive triple-negative breast cancer (TNBC) who received first-line sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (n = 221) achieved a median PFS2 that was not reached (NR; 95% CI, NR-NR) vs 21.0 months (95% CI, 16.0-NR) among those who received chemotherapy plus pembrolizumab (n = 222; stratified HR, 0.67; 95% CI, 0.48-0.95).¹¹

“This [PFS2] end point was exploratory,” Kevin Kalinsky, MD, MS, FASCO, of the Winship Cancer Institute of Emory University in Atlanta, Georgia, stated in an interview with OncLive. “In totality, even when we look at time to first subsequent therapy or time to second subsequent therapy, we’re seeing that sacituzumab govitecan plus pembrolizumab is offering clinical benefit for our patients. [When giving] an antibody-drug conjugate [ADC] plus a checkpoint inhibitor, there’s been this hypothesis that there’s an immunogenic cell death, and it’s affecting the immune milieu; these data support that. Also, given that for PD-L1–negative patients, we’re now giving an ADC in the frontline setting, [these data] reiterate the fact that ADCs are frontline therapy, both for patients with PD-L1–positive as well as PD-L1–negative tumors.”

Another prespecified exploratory analysis of this trial showed that sacituzumab govitecan plus pembrolizumab elicited PFS benefits vs chemotherapy plus pembrolizumab across biomarker subgroups.¹²

“When we looked across different levels of TROP2 [expression], sacituzumab govitecan plus pembrolizumab always did better than chemotherapy plus pembrolizumab,” Sara Tolaney, MD, MPH, of Dana-Farber Cancer Institute in Boston, Massachusetts, said in another interview with OncLive. “Additionally, when we looked at BRCA mutation status, we similarly saw that sacituzumab govitecan plus pembrolizumab did better than chemotherapy plus pembrolizumab, and we saw that…irrespective of HER2 expression status. Overall, the combination of sacituzumab govitecan plus pembrolizumab is always doing better than chemotherapy plus pembrolizumab. Overall, [these data] support the use of sacituzumab govitecan plus pembrolizumab, irrespective of biomarker status, in patients who have previously untreated metastatic TNBC that is PD-L1 positive.”

Additionally, data from a prespecified exploratory analysis of the phase 3 ASCENT-03 trial (NCT05382299) showed that among patients with previously untreated TNBC who were not eligible to receive PD-(L)1 inhibition, sacituzumab govitecan monotherapy generated improved PFS vs chemotherapy across all subgroups, regardless of TROP2 expression, BRCA mutation status, and HER2 status.¹³

What is the efficacy of gedatolisib in PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer?

Gedatolisib (PF-05212384) elicited statistically significant and clinically meaningful improvements in PFS when combined with fulvestrant and palbociclib, as well as in combination with fulvestrant alone, vs alpelisib (Piqray) plus fulvestrant in the cohorts of patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer.¹⁴

Topline results from the phase 3 VIKTORIA-1 trial (NCT05501886) showed that among patients in the gedatolisib arm (n = 155), the median PFS was 11.1 months (95% CI, 9.0-16.7) vs 5.6 months (95% CI, 5.2-7.4) in the alpelisib arm (n = 155; HR, 0.50; 95% CI, 0.37-0.68; P < .0001).

“From an efficacy standpoint, these results are real,” Sara A. Hurvitz, MD, FACP, of Fred Hutchinson Cancer Center in Seattle, Washington, said in an interview with OncLive. “We have moved the needle in terms of efficacy, but what I would say is almost more important is we’ve substantially moved the needle in terms of toxicity. Maybe because of [gedatolisib’s] intravenous formulation, we’re seeing a much better safety profile in terms of gastrointestinal adverse effects, hyperglycemia, and rash, and that’s a big win for patients when you put all the evidence together.”

What secondary end point data from TROPION-Breast02 are important to highlight?

Datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) generated statistically significant improvements in time to first subsequent therapy or death (TFST), PFS2, and time to second subsequent therapy or death (TSST) compared with investigator’s choice of chemotherapy in patients with locally recurrent inoperable or metastatic TNBC who were not eligible to receive immunotherapy.¹⁵

Data from the phase 3 TROPION-Breast02 trial (NCT05104866) presented at ASCO 2026 showed that a median follow-up of 27.5 months (range, 13.3-38.7), the median TFST was 10.9 months (95% CI, 9.5-12.1) in the Dato-DXd arm (n = 323) compared with 5.6 months (95% CI, 4.9-6.3) in the chemotherapy arm (n = 321; HR, 0.49; 95% CI, 0.41-0.59). The median PFS2 values were 15.6 months (95% CI, 13.3-17.4) and 11.8 months (95% CI, 10.9-12.8), respectively (HR, 0.61; 95% CI, 0.50-0.74). The median TSST values were 16.7 months (95% CI, 15.2-19.5) vs 12.6 months (95% CI, 11.3-13.6), respectively (HR, 0.67; 95% CI, 0.55-0.81).

Previously, in May 2026, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic TNBC who are not eligible for PD-1/PD-L1 inhibitor therapy; this approval was backed by data from TROPION-Breast02.¹⁶

What is the prognostic value of ctDNA status in early TNBC?

Post-surgery ctDNA status was found to be highly prognostic for distant recurrence in patients with early TNBC, and measuring this status with a whole-genome sequencing (WGS) assay outperformed pathologic complete response (pCR) status for stratifying prognostic risk.¹⁷Data from a prospective sub-study of the phase 2/3 PARTNER trial (NCT03150576) presented at ASCO 2026 demonstrated a post-surgery positive predictive association of 100% between WGS and whole-exome sequencing assays.

“ctDNA status at that 2-to-4–week post-surgery time point gave better prognostic information than pCR [status], so this was a significant predictor for distant relapse–free interval,” Ruta D. Rao, MD, of the RUSH University Cancer Center in Chicago, Illinois, said in an interview with OncLive.

Watch Dr Rao’s full commentary below:

What were the long-term outcomes with T-DXd plus pertuzumab in HER2-positive advanced/metastatic breast cancer?

Patients with HER2-positive advanced or metastatic breast cancer who achieved a complete response (CR) or deep partial response (PR) with T-DXd plus pertuzumab achieved long-term outcome improvements vs patients who achieved less deep responses.¹⁸ Findings from an exploratory analysis of the phase 3 DESTINY-Breast09 trial (NCT04784715) presented at ASCO 2026 showed that among patients who received T-DXd/pertuzumab (n = 377), the 24-month PFS rate was 85.1% (95% CI, 72.2%-92.3%) in patients who achieved a CR (n = 58), 80.0% (95% CI, 71.7%-86.1%) in those who achieved a deep PR (n = 141), 64.3% (95% CI, 54.3%-72.8%) in those who achieved a PR of less than 80% (n = 127), and 35.5% (95% CI, 21.1%-50.2%) in those with best responses of stable disease (SD) or progressive disease (PD; n = 51).

“Depth of response does matter in terms of trying to understand long-term efficacy,” Tolaney stated in another interview with OncLive. “Deep responses matter because [they are] associated with good PFS.”

Watch more of Tolaney’s commentary below:

References

1. Pusztai L, Harbeck N, Boileau J, et al. Residual cancer burden (RCB) following neoadjuvant treatment (NAT) with trastuzumab deruxtecan (T-DXd) followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in highrisk HER2+ early-stage breast cancer (eBC). Presented at: 2025 ESMO Breast Cancer Congress. May 6-8, 2026; Berlin, Germany. Abstract LBA1.
2. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. FDA. May 15, 2026. Accessed July 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage
3. Rugo HS, Oliveira M, Howell S, et al. Capivasertib (C) and fulvestrant (F) for patients (pts) with HR+/HER2_ advanced breast cancer (ABC): final overall survival (OS) results from the phase 3 CAPItello-291 trial. Presented at: 2025 ESMO Breast Cancer Congress. May 6-8, 2026; Berlin, Germany. Abstract 417O.
4. Schmid P, Geyer CE Jr, Martín M, et al. Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+, HER2- eBC) in the phase III lidERA BC clinical trial: results by menopausal status. J Clin Oncol. 2026;44(suppl 16):502. doi:10.1200/JCO.2026.44.16_suppl.502
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 July 13, 2026. https://www.roche.com/media/releases/med-cor-2026-06-02
6. Jhaveri KL, Rugo HS, Tolaney SM, et al. Post-progression treatment analyses of evERA Breast Cancer (BC): a phase III trial of giredestrant (GIRE) + everolimus (E) in patients with ER-positive, HER2-negative advanced BC previously treated with a CDK4/6 inhibitor. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 1016.
7. Turner N, et al. Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): primary analysis of the phase III persevERA BC trial. J Clin Oncol. 2026;44(suppl 17):LBA1006. doi:10.1200/JCO.2026.44.17_suppl.LBA1006
8. Stein RC, Makris A, Macpherson IR, et al. First results from the OPTIMA phase III randomized non-inferiority trial of test-directed chemotherapy in patients with high clinical risk ER-positive HER2-negative early breast cancer: a pre-planned time-driven analysis. J Clin Oncol. 2026;44(suppl 16):500. doi:10.1200/JCO.2026.44.16_suppl.500
9. Schmid P. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: final analysis results from the phase 3 KEYNOTE-522 study. J Clin Oncol. 2026;44(suppl 16):507. doi:10.1200/JCO.2026.44.16_suppl.507
10. 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
11. Kalinsky K, Schmid P, de Azambuja E, et al. Progression-free survival after next line of treatment (PFS2) and subsequent therapies in the ASCENT-04 study of participants with previously untreated PD-L1+ metastatic triple-negative breast cancer treated with sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract LBA1000.
12. Tolaney SM, Schmid P, de Azambuja E, et al. ASCENT-04: Analysis of efficacy by biomarker subgroups with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in participants (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2026;44(suppl 16):1013. doi:10.1200/JCO.2026.44.16_suppl.1013
13. Barrios C, Hurvitz SA, Tolaney SM, et al. ASCENT-03: Efficacy by biomarker subgroup with sacituzumab govitecan (SG) vs chemotherapy (chemo) in participants (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors (PD-[L]1i). J Clin Oncol. 2026;44(suppl 16):1014. doi:10.1200/JCO.2026.44.16_suppl.1014
14. 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 (MT) advanced breast cancer (VIKTORIA-1 study 2). J Clin Oncol. 2026;44(suppl 17):LBA1008. doi:10.1200/JCO.2026.44.17_suppl.LBA1008
15. Cescon DW, Traina TA, 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: additional efficacy endpoints from the TROPION-Breast02 study. J Clin Oncol. 2026;44(suppl 16):1002. doi:10.1200/JCO.2026.44.16_suppl.1002
16. 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 May 22, 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
17. Dooley A, Fontenele RS, Grasse G, et al. Evaluation of whole-exome and whole-genome sequencing tumor-informed circulating tumor DNA MRD assays in patients with early triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy (NAC) with or without olaparib: a prospective sub-study of the PARTNER trial. J Clin Oncol. 2026;44(suppl 16):570. doi:10.1200/JCO.2026.44.16_suppl.570
18. Park YH, Tolaney SM, Saura C, et al. A DESTINY-Breast09 analysis of treatment duration and clinical outcomes by best response to trastuzumab deruxtecan (T-DXd) + pertuzumab (P). Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, Illinois. Abstract 1021.