Breast Cancer Experts Spotlight Practice-Informing and Thought-Provoking Data From ASCO 2026

Throughout the 2026 ASCO Annual Meeting, OncLive® spoke with leading breast oncologists to capture their perspectives on potentially practice-changing presentations that may soon translate into clinical practice.

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).

Findings from study 2 of the VIKTORIA-1 trial (NCT05501886) showed that multi-PAM inhibition with gedatolisib (PF-05212384) plus fulvestrant (Faslodex) with or without palbociclib (Ibrance) significantly improved progression-free survival (PFS) outcomes vs alpelisib (Piqray) plus fulvestrant in patients with hormone receptor–positive, HER2-negative, PIK3CA-mutant advanced breast cancer.¹

At a median follow-up of 12.8 months (interquartile range, 7.5-19.9), patients who received the gedatolisib-based triplet (n = 155) achieved a median PFS of 11.1 months (95% CI, 9.0-16.7) vs 5.6 months (95% CI, 5.2-7.4) in the control arm (n = 155; adjusted HR, 0.50; 95% CI, 0.37-0.68; P < .0001). Additionally, the median PFS in the gedatolisib doublet arm (n = 52) was 11.3 months (95% CI, 9.1-22.1; HR vs control arm, 0.51; 95% CI, 0.33-0.79; P = .0013).

Virginia Kaklamani, MD, DSc

UT Health San Antonio MD Anderson Cancer Center

“The data from VIKTORIA-1 were interesting. Gedatolisib is a novel mTOR/PI3K inhibitor. We had data already [from this trial] in the patient population that did not have PIK3CA mutations. Now we have data in the PIK3CA-mutated subset, showing that gedatolisib outperformed alpelisib. This agent is likely going to get approved. The issue is toxicity. Stomatitis [is associated with gedatolisib]. [It is also an] intravenous [formulation, given for] 3 weeks on and 1 week off. However, this is something that is going to help give us more options for our patients.”

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.

Primary results from the phase 3 OPTIMA trial (ISRCTN42400492) showed that adjuvant treatment guided by the 50-gene Prosigna assay was noninferior to the standard treatment approach of chemotherapy followed by endocrine therapy in patients with estrogen receptor (ER)–positive, HER2-negative early breast cancer at high clinical risk.² Based on these outcomes, investigators determined that the genomic assay can accurately identify patients who do not receive a meaningful survival benefit from adjuvant chemotherapy.

In the per-protocol population, the 5-year invasive breast cancer–free survival (IBCFS) rate was 90.3% (95% CI, 88.5%-91.8%) in the test-directed arm (n = 2094). In the control arm (n = 2059), the 5-year IBCFS rate was 91.8% (95% CI, 90.1%-93.2%). The trial successfully met its pre-established 3% noninferiority margin (adjusted HR, 1.03; 90% CI, 0.85-1.25; P = .006).

“We already have other genomic assays. We have the 21-gene recurrence score and the 70-gene recurrence score, and so forth. [Prosigna] is a newer one. How are we going to use it? There are a couple things on that trial that were interesting. One is the fact that all patients who were premenopausal received ovarian suppression, and there was no chemotherapy benefit, which points to the importance of ovarian suppression in that patient population. Trials like the phase 3 OFSET trial [NCT05879926] that are evaluating that makes it even more important that we accrue to these trials as quickly as we can. [OPTIMA] evaluated patients with 4 or more positive lymph nodes. If those patients want to try to avoid chemotherapy, then [OPTIMA] has the data [to support] that.”

Paolo Tarantino, MD, PhD

Dana-Farber Cancer Institute

“This is a trial testing a new biomarker to try to de-escalate chemotherapy in patients who do not benefit from it. The results are promising. The follow-up is a bit short, so we need longer follow-up, but if the data are confirmed, we may be doing less unnecessary chemotherapy in the future, even for patients with multiple positive nodes, and for younger patients. That brings a lot of hope with this new biomarker, PAM50. Fingers crossed for these data to hold when we have longer follow-up.”

Frederick Howard, MD

University of Chicago Medicine

“[These data] answer key questions from discussions that I have frequently with both premenopausal women about the utility of chemotherapy—hopefully we’ll be able to de-escalate there, as well as for patients who have more than 3 [positive] lymph nodes involved.”

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.

Findings from the overall survival (OS) analysis of the SENOMAC trial (NCT02240472) showed that in patients with breast cancer and 1 to 2 sentinel lymph node macrometastases, the omission of complete axillary dissection did not worsen survival outcomes or relapse rates and should be the standard of care.³ The OS and recurrence rates in the omission arm were noninferior to those in patients who underwent compete axillary lymph node dissection.

Among patients who underwent compete axillary lymph node dissection (n = 1205), the 5-year OS rate was 93.4% (95% CI, 91.9%-94.9%); this rate was 94.4% (95% CI, 93.1%-95.7%) among patients in whom complete axillary lymph node dissection was omitted (n = 1335; HR, 0.89; 95% CI, 0.67-1.17; P < .001). In the compete axillary lymph node dissection arm, the rates of local recurrence, regional recurrence, distant recurrence, death from any cause, and death from breast cancer were 1.2%, 0.6%, 5.5%, 8.3%, and 3.2%, respectively. These respective rates in the omission arm were 1.3%, 0.7%, 4.9%, 7.7%, and 2.6%.

Robert Stein, MA, MB BChir, PhD, FRCP

University College London

“[One] study that’s been important for breast cancer is SENOMAC, because I think that is going to change how surgeons operate. [Between OPTIMA and SENOMAC], we’ve shown that we can do significantly less treatment for a lot of our patients and get the same results.”

First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer (ABC): Final progression-free survival 2 (PFS2) from the phase III SERENA-6 trial.

Final time to second progression (PFS2) data from the phase 3 SERENA-6 trial (NCT04964934) showed a significant benefit with switching to camizestrant and continuing to receive a CDK4/6 inhibitor vs continuing standard aromatase inhibition plus a CDK4/6 inhibitor in patients with ER-positive, HER2-negative advanced breast cancer who developed emergent ESR1 mutations prior to radiographic progression.⁴

Patients in the camizestrant arm (n = 157) achieved a median PFS2 of 25.7 months (95% CI, 20.4-30.3), whereas those in the control arm (n = 158) had a median PFS2 of 19.1 months (95% CI, 16.8-21.0; HR, 0.63; 95% CI, 0.46-0.86; P = .00373). At the 30-month interval, the PFS2 rates were 41.5% for the camizestrant arm and 29.7% for the aromatase inhibitor arm. These findings were supported by a supplementary analysis using RECIST 1.1 criteria, which showed a similar PFS2 advantage for camizestrant (HR, 0.64; 95% CI, 0.46-0.90; nominal P = .0094).

Mabel Mardones, MD

Rocky Mountain Cancer Centers

“SERENA-6 has been contentious, but the PFS and circulating tumor DNA data are thought-provoking in the post–CDK4/6 inhibitor setting.”

Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-03 study of participants (pts) with previously untreated metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) vs chemotherapy (chemo).

A post hoc analysis of the phase 3 ASCENT-03 trial (NCT05382299) revealed that first-line treatment with sacituzumab govitecan-hziy (Trodelvy) significantly extended median PFS2 compared with standard chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic TNBC who are not candidates for PD-(L)1 inhibition.⁵

With a median follow-up of 13.2 months (range, <0.1-29.2), the median PFS2 in the sacituzumab govitecan arm (n = 279) was 18.2 months (95% CI, 15.9-not reached). In contrast, patients in the control arm (n = 143), who received chemotherapy, had a median PFS2 of 14.0 months (95% CI, 12.5-17.4; HR, 0.70; 95% CI, 0.55-0.90). This benefit was evident despite a high crossover rate from the control arm to the investigational arm.

Nan Chen, MD

University of Chicago Medicine

“The PFS2 data from ASCENT-03 were interesting. One of the concerns we had about the ASCENT-03 data initially was that there wasn’t a benefit of OS in comparison with chemotherapy. However, despite the significant crossover of patients from the chemotherapy arm to receiving sacituzumab govitecan, there was still a benefit in PFS2, suggesting that we probably should be moving up sacituzumab govitecan to earlier lines.”

References

1. 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
2. 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
3. de Boniface J, Txedskov TF, Rydén 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 16):LBA503. doi:10.1200/JCO.2026.44.16_suppl.LBA503
4. 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
5. Hurvitz SA, Cortes J, Tolaney SM et al. Progression-free survival after next line of treatment (PFS2) and subsequent therapies (subs tx) in the ASCENT-03 study of participants (pts) with previously untreated metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) vs chemotherapy (chemo). J Clin Oncol. 2026;44(suppl 17):1001. doi:10.1200/JCO.2026.44.17_suppl.1001