Anticipated Data and Practice-Changing Trials: An ASCO 2026 Breast Cancer Preview

The upcoming 2026 American Society of Clinical Oncology (ASCO) Annual Meeting is poised to showcase pivotal data that could reframe treatment paradigms across the breast cancer spectrum, from early-stage de-escalation strategies to novel therapeutics for advanced disease. Ahead of the meeting, MinhTri Nguyen, MD, and Nerea Lopetegui, MD, shared their insights with CancerNetwork® on the specific clinical trials, regulatory debates, and emerging modalities generating the most significant professional anticipation.

Key discussions at the conference will center around the clinical utility of early therapeutic switching upon biomarker detection vs waiting for radiographic progression, as well as the ongoing integration of novel bispecific antibodies and antibody-drug conjugates (ADCs). From highly debated regulatory decisions to practice-changing "underdog" studies evaluating the omission of standard chemotherapy and axillary dissections, these presentations represent crucial milestones in the pursuit of more personalized, patient-centered oncology care.

Nguyen is a breast medical oncologist and Lopetegui-Lia is a breast medical oncologist at The Ohio State University Comprehensive Cancer Center. Both are part of the editorial advisory board for ONCOLOGY®.

SERENA-6: Camizestrant in ESR1-Mutated Breast Cancer

Nguyen believes this study is going to “make a big splash” at 2026 ASCO, even after the vote from the FDA’s Oncology Drugs Advisory Committee (ODAC), which voted 6 to 3 against the new drug application for camizestrant for adult patients with hormone receptor (HR)–positive, HER2-negative locally advanced or metastatic breast cancer with emerging ESR1 mutations.¹

The phase 3 SERENA-6 trial (NCT04964934) findings showed a median progression-free survival (PFS) of 16.0 months (95% CI, 12.7-18.2) in the camizestrant group vs 9.2 months (95% CI, 7.2-9.5) in the aromatase inhibitor (AI) group (HR, 0.44; 95% CI, 0.31-0.60; P <.00001).² The median time to deterioration was 23.0 months (95% CI, 13.8-not calculable) vs 6.4 months (95% CI, 2.8-14.0) in the AI arm (HR, 0.53; 95% CI, 0.33-0.82; P <.001). Additionally, the PFS2 results were sustained through the next line of therapy (HR, 0.52; 95% CI, 0.33-0.81; P = .0038).

“The trial was successful [statistically]. The primary end points were met, but it lands itself in this weird regulatory environment where the ODAC meeting was explicitly questioning the trial design. The question is for the community, and the buzz about it––and [what] the FDA correctly identified––is, whether early switching at ESR1 mutation detection genuinely is better than waiting for radiographic progression, and I don’t think SERENA-6 answers that question,” Nguyen said.

Francois Clement Bidard, MD, PhD, will present the results on June 2^nd from 11:57 to12:09 pm CDT.³

Bispecifics in the Breast Cancer Space

Izalontamab brengitecan (iza-bren) an EGFRxHER2 bispecific antibody drug conjugate is being studied in patients with unresectable locally advanced or metastatic triple-negative breast cancer who have disease progression after taxane therapy.⁴

Results are to be presented as part of a phase 3 trial (NCT06382142). The pre-specified interim analysis showed a statistically significant and clinically meaningful improvement in the PFS and overall survival (OS) vs physician’s choice of therapy. Additionally, the primary end points were met.

“Other cancer subtypes, such as multiple myeloma, uveal melanoma, lung cancer, and others have been using bispecifics with promising results, so it’s nice to see a bispecific agent moving towards translation, and potentially commercialization in the breast cancer space, especially in triple-negative breast cancer, where there’s a high unmet need for better treatments,” Lopetegui-Lia said.

Jiong Wu, MD, PhD, will present results on June 2^nd from 10:45 to 10:57 am CDT.⁵

Additionally, the use of rilvegostomig plus fam-trastuzumab deruxtecan-nxki (Enhertu) will be assessed in the phase 2 I-SPY 2.2 trial (NCT01042379). Patients with high-risk HER2-negative breast cancer were included in this trial. Rilvegostomig is an investigational bispecific monoclonal antibody that simultaneously targets the PD-1 and TIGIT pathways.

The detailed efficacy data, including the pathological complete response and biomarker responses will be presented during 2026 ASCO.

“The rationale is dual immune checkpoint inhibition will potentially have greater T cell activation than PD-1 blockade alone. It is a novel immunotherapy combined with an ADC, which is T-DXd, which we’re all familiar with. Excited to see the results of this study as well,” Lopetegui-Lia said.

Ciara Catherine O’Sullivan, MBBCh, will present the trials on June 1^st from 10:45 to 10:51 am CDT.⁶

The Standout Stars

“The story with giredestrant is one of the most interesting in breast oncology right now, and persevERA is an abstract that attempts to add to that story, but ultimately makes us ponder a bit more, and maybe even confused a bit more,” Nguyen said.

In a press release from March 2026, the phase 3 trial (NCT04546009) did not meet the primary end point of statistically significant improvement in PFS for the intent-to-treat population vs letrezole plus palbociclib (Ibrance) for patients with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer.⁷ Of note, a numerical improvement was observed, and the adverse effect profile was manageable and consistent with other safety profiles for each individual agent.

“I am hopeful we can better understand why the results did not meet its primary end point, particularly [considering] the positive results in the adjuvant setting from the lidERA trial. Clarifying where oral SERDs truly fit within our treatment paradigm, identifying which patients derive the greatest benefit, and how to best combine and sequence them with CDK4/6 inhibitors and PIK3/AKT-targeting agents will be key in optimizing outcomes,” Lopetegui-Lia said.

“Maybe it’s not very good with that comparator arm, but what we know so far is that it’s not ready to, or at least oral SERDs aren’t ready to displace this combination of frontline setting just yet. Combination strategies continue to be planned; they’re continuing to push the field forward. I look forward to those future studies, and hopefully that will complete the picture for us,” Nguyen said.

Nicholas C. Turner, MD, PhD, will present the results on June 2^nd from 11:45 to 11:57 am CDT.⁸

The Underdogs of ASCO Breast

OPTIMA and SENOMAC

The phase 3 OPTIMA trial (ISRCTN42400492) compared chemotherapy decisions made with Prosigna gene expression tests with standard treatment for patients who had node-positive breast cancer. A total of 280 invasive breast cancer-free survival events occurred with 66% being distant recurrences. The 5-year IBCFS rate was 91.5% (95% CI, 89.7%-92.9%) in the control arm and 90.4% (95% CI, 88.6%-92.0%) in the test-directed arm (HR, 0.99; 90% CI, 0.81-1.20; P = .013).

“OPTIMA attempts to complete this roadmap that we use for de-escalation in the hormone positive for HER2-negative early breast cancer situation… if the results of this study were positive, and we are able to guide patients through chemotherapy emission with the genetic testing or genomic testing, this could be practice changing for these patient populations that we currently just give chemotherapy by default, because we don’t have the data,” Nguyen said.

Lopetegui-Lia also noted, “The investigators explicitly acknowledge that existing genomic assay data carry greater uncertainty in premenopausal patients. While prior randomized trials demonstrated a chemotherapy benefit in premenopausal women, ovarian function suppression was used inconsistently across those studies. As a result, it remains unclear whether the observed benefit reflects a direct cytotoxic effect or is largely attributable to chemotherapy-induced ovarian suppression. By OPTIMA incorporating contemporary endocrine therapy, including OFS for premenopausal women, it is uniquely positioned to better understand these effects. I believe this is one of the most clinically relevant aspects of the study.”

Robert C. Stein, PhD, MBBCir, FRCP, will present the results on May 30^th from 1:15 to 1:27 pm CDT.⁹

The SENOMAC trial (NCT02240472) looked at omission of complete axillary lymph node dissection for patients with clinically node-negative breast cancer who have sentinel lymph node metastases who have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data with relevant subgroups.

Previous results showed that the 5-year recurrence-free survival was 89.7% (95% CI, 87.5%-91.9%) in the sentinel lymph node biopsy group and 88.7% (95% CI, 86.3%-91.9%) in the dissection group (HR, 0.89; 95% CI, 0.66-1.19; P <.001).¹⁰

“This was already read out and published in the New England Journal Medicine in April 2024, but the new data that we’re getting from ASCO is the overall survival data and the comorbidity outcomes data. They have mature OS data, which was the primary analysis point, it was the primary end point in which the trial was powered for, and then also patient-reported and clinician-reported morbidity data, which I would argue is probably clinically more meaningful,” Nguyen said.

Jana de Boniface, MD, PhD, will report these results on May 30^th from 2:15 to 2:27 pm CDT.¹¹

References

1. April 30, 2026 meeting of the Oncologic Drug Advisory Committee (ODAC). YouTube. Accessed May 22, 2026. https://tinyurl.com/5cry64pu
2. Turner NC, Mayer EL, 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
3. Bidard FC, Mayer EL, Park YH, et al. First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer (ABC): final progression-free survival 2 (PFS2) from the phase 3 SERENA-6 trial. J Clin Oncol. 2026;44(supl 17):LBA1007. doi:10.1200'JCO.2026.44.17_suppl.LBA1007
4. SystImmune and Bristol Myers Squibb highlight positive phase III interim topline results for izalontamab brengitecan (iza-bren) in previously treated unresectable locally advanced or metastatic triple-negative breast cancer. News release. Bristol Myers Squibb. February 26, 2026. Accessed May 22, 2026. https://tinyurl.com/6dtzawca
5. Wu J, Zhang J, Ouyang Q, et al. Izalontamab brengitecan (iza-bren) versus physician's choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC): a randomized phase III study. J Clin Oncol. 2026;44(suppl 17):LBA1003. doi:10.1200/JCO.2026.44.17_suppl.LBA1003
6. O'Sullivan CC, Kalinsky K, Yau C, et al. Neoadjuvant rilvegostomig (R) + trastuzumab deruxtecan (T-DXd) in high-risk HER2 negative breast cancer: results from the I-SPY 2.2 trial. J Clin Oncol. 2026. 44(suppl 17):LBA514. doi:10.1200'JCO.2026.44.17_suppl.LBA514
7. Genentech provides update on phase III persevERA Study in ER-positive advanced breast cancer. News release. March 8, 2026. Accessed May 22, 2026. https://tinyurl.com/372k3x9v
8. Turner NC, Jhaveri KL, Bardia A, 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
9. Stein RC, Makris A, Macpherson IR, et al. Final 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. J Clin Oncol. 2026;44(suppl 16):500. doi: 10.1200/JCO.2026.44.16_suppl.500
10. de Boniface J, Filtenborg Tvedskov T, Rydén L, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024;390(13):1163-1175. doi:10.1056/NEJMoa2313487
11. Boniface JD, Tvedskov TF, Ryden L, et al. Omission of completion axillary dissection in patients with breast cancer and sentinel lymph node macrometastases: overall survival and patient-reported arm morbidity from the randomized SENOMAC trial. J Clin Oncol. 2026; 44(suppl 17):LBA503. doi:10.1200/JCO.2026.44.17_suppl.LBA503