Best of ASCO Las Vegas 2026: Metastatic Breast Cancer Updates
Presenter: Lee Schwartzberg, MD, FACP
Conference: Best of ASCO Las Vegas
The Bottom Line
At the 2026 Best of ASCO Las Vegas conference presented by Total Health, Dr Lee Schwartzberg reviewed an evolving metastatic breast cancer (MBC) landscape in which many of the most informative presentations were not necessarily new primary analyses, but longer-term follow up and subgroup evaluations addressing whether an initial treatment benefit persists beyond first progression. This placed a particular emphasis on the endpoints like progression-free survival 2 (PFS2), time to subsequent therapy, and/or the ability to delay chemotherapy or use of antibody-drug conjugates (ADCs). Across the spectrum of hormone receptor (HR)-positive/HER2-negative (HR+/HER2−), HER2-positive, and triple-negative breast cancer (TNBC), an emerging theme was the use of increasingly effective treatment earlier in the disease course, coupled with a more patient-specific, molecularly informed selection of treatment. The most immediately practice-changing data presented by Dr Schwartzberg, however, came from supportive care: specifically, reduced-frequency denosumab administered every 12 weeks was noninferior to every-4-week treatment for preventing symptomatic skeletal events (SSEs), with notably less toxicity and a substantially lower treatment burden and cost.
HR+/HER2− MBC: Treating Molecular Progression Before Radiographic Progression
The SERENA-6 trial provided perhaps the clearest example of a changing treatment paradigm. In this study, patients receiving first-line aromatase inhibitor (AI) plus a CDK4/6 inhibitor underwent serial circulating tumor DNA (ctDNA) testing. Those who developed an ESR1 mutation without radiographic disease progression were randomized to switch the AI to the oral SERD camizestrant while continuing their existing CDK4/6 inhibitor, or to continue AI plus CDK4/6 inhibition. With longer follow-up, median PFS was 16.8 months with camizestrant versus 9.2 months with continued AI (hazard ratio [HR] = 0.45). Importantly, Dr Schwartzberg noted that the treatment advantage persisted beyond first progression: median PFS2 was 25.7 versus 19.1 months (HR = 0.63; P=.00373). Camizestrant also prolonged chemotherapy/ADC-free survival (22.6 vs 18.7 months; HR = 0.64) and reduced deterioration in several patient-reported measures. Overall survival (OS) data were immature and not different between groups, however, the molecular effect was striking as well: total ctDNA clearance occurred in 51% versus 2% of patients receiving camizestrant versus the continued AI. Dr Schwartzberg emphasized that delaying chemotherapy or an ADC is increasingly a clinically meaningful endpoint: “Patients are very interested in this [endpoint]: ‘Do I have to go on to chemotherapy?’ And we’re seeing this more in trials now, and I think it’s a good thing because it relates to real-world practice.” Taken together, he believes the findings support a potentially important shift away from waiting for radiographic progression and toward detecting emerging endocrine resistance molecularly and further, intervening before conventional progression occurs.
Dr Schwartzberg also highlighted two giredestrant studies which added some nuance in this setting. In persevERA BC, he noted that first-line giredestrant plus palbociclib produced a numerical but statistically nonsignificant improvement in PFS versus letrozole plus palbociclib (33.1 versus 28.2 months; HR = 0.89; P=.1553). ORR and clinical benefit rate were also similar, although duration of response favored giredestrant numerically (38.5 versus 30.4 months). Dr Schwartzberg therefore characterized persevERA as a negative trial despite the numerical differences.
By contrast, he noted a follow-up from the evERA BC study, evaluating giredestrant plus everolimus after prior CDK4/6 inhibition, which reinforced the previously reported efficacy of this combination. The PFS2 and chemotherapy-free survival endpoints favored giredestrant plus everolimus, with the largest numerical effects among patients with ESR1-mutated disease. These analyses suggested that the benefit achieved before first progression was maintained into subsequent therapy, supporting continued investigation of giredestrant-based strategies after CDK4/6 inhibitor resistance.
HER2-Positive MBC: Expanding Maintenance Therapy
Dr Schwartzberg then reviewed findings from HER2CLIMB-05 which evaluated adding tucatinib to trastuzumab plus pertuzumab (HP) maintenance after 4 to 8 cycles of first-line taxane plus HP. Tucatinib improved median investigator-assessed PFS from 16.3 to 24.9 months, a gain of 8.6-months (HR = 0.641; P<.0001). The ASCO analysis also explored whether that benefit extended across clinically important subgroups. Benefit was observed in both HR-positive and HR-negative disease, in patients with or without baseline/history of brain metastases, and in both de novo and recurrent metastatic disease. Dr Schwartzberg noted that the magnitude appeared particularly substantial in those with HR-negative disease, while the HR-positive subgroup also benefited. The safety profile remained similar across subgroups. The findings support tucatinib plus HP as a potential maintenance strategy across a broad HER2-positive MBC population, with Dr Schwartzberg highlighting patients with HR-negative tumors, or a history of brain metastases as groups of particular clinical interest in this trial.
TNBC: ADCs Continue Their Move Into the First Line
Perhaps the strongest therapeutic theme was the rapid movement of ADCs into first-line metastatic TNBC. For patients who are not candidates for PD-(L)1 inhibition, Dr Schwartzberg noted results from the ASCENT-03 trial which compared first-line sacituzumab govitecan (SG) with chemotherapy. SG had previously reduced the risk of progression or death by 38%, and the newly reported analysis demonstrated that its advantage extended through subsequent therapy. Median PFS2 was 18.2 versus 14.0 months (HR = 0.70), a result seen despite an unusually high crossover rate: 82% of patients initially receiving chemotherapy subsequently received SG. Twelve-month PFS2 rates were 71% versus 59%, and 18-month rates were 52% versus 41%. Dr Schwartzberg considered the crossover particularly informative because real-world patients do not invariably reach subsequent treatment. In his view, the results strengthen the argument for using the most effective therapy early, rather than reserving it for later lines.
TROPION-Breast02 similarly evaluated first-line datopotamab deruxtecan (Dato-DXd) against investigator’s-choice chemotherapy in patients for whom immunotherapy was not an option. Previously reported dual-primary endpoint results showed median PFS of 10.8 versus 5.6 months (HR = 0.57; P<.0001), a median OS of 23.7 versus 18.7 months (HR = 0.79; P=.029) and ORR was 63% versus 29%. At ASCO, Dr Schwartzberg noted improved PFS2 and time to subsequent therapies which further demonstrated that the initial Dato-DXd benefit was maintained beyond first progression.
Lastly, for PD-L1–positive TNBC, Dr Schwartzberg noted results from ASCENT-04 which evaluated SG plus pembrolizumab versus chemotherapy plus pembrolizumab. The previously reported median PFS was 11.2 versus 7.8 months (HR = 0.65). He cited new exploratory analyses which show that the advantage of SG plus pembrolizumab was observed across Trop-2 expression quartiles, tumor BRCA-mutated and wild-type disease, and both HER2 IHC 0 and HER2-low tumors. Although he cautioned that many subgroup sample sizes were small and the analyses were descriptive, the consistency of results argue against using these biomarkers to identify patients who should or should not receive SG.
Taken together Dr Schwartzberg views these trials as establishing an increasingly ADC-centered first-line approach to metastatic TNBC: “We should generally not be giving chemotherapy to our first-line metastatic triple-negative patients anymore. We have ADCs now that do the job better.”
A Practice-Changing Supportive-Care Finding: Less-Frequent Denosumab
In the final portion of his presentation, Dr Schwartzberg discussed what he considered this year’s ASCO most immediately practice-changing result. The phase III REDUSE 96/12 trial enrolled 1,380 patients with bone metastases from metastatic breast cancer or metastatic castration-resistant prostate cancer and compared denosumab 120 mg, administered every 4 weeks with every 12 weeks, following an induction phase. Notably, every-12-week denosumab was noninferior for time to first SSE (HR = 1.023; 90% CI = 0.874–1.197), while producing significantly less hypocalcemia and fewer osteonecrosis of the jaw/tooth-infection events. OS was also equivalent, and the less-frequent schedule reduced drug costs by 53% per patient. Dr Schwartzberg also highlighted the long follow-up which provided a useful reminder that skeletal risk persists: SSEs continued to occur as late as 5 years, emphasizing the need for long-term bone-directed management in patients living longer with MBC. As such, he strongly recommended moving appropriate patients to 12-week dosing, citing equivalent skeletal protection alongside lower toxicity, financial burden, and associated disruption to patients’ lives.
Conclusions and Faculty Insights
The 2026 ASCO metastatic breast cancer data as highlighted by Dr Schwartzberg illustrate a broader evolution from simply asking whether a therapy delays first progression to asking how long its benefit persists, whether it delays more a burdensome treatment, and whether treatment can be adapted before radiographic progression occurs. SERENA-6 may ultimately establish serial ctDNA monitoring for emergent ESR1 mutations as a new therapeutic decision point in HR+/HER2− MBC. HER2CLIMB-05 suggests that tucatinib can further strengthen first-line HER2-directed maintenance, while ASCENT-03, TROPION-Breast02, and ASCENT-04 collectively accelerate the movement of ADCs into first-line TNBC.
Dr Schwartzberg appropriately distinguished investigational strategies from what clinicians could change immediately: at the time of his presentation, he noted that camizestrant and giredestrant were not yet FDA approved for the uses discussed. By contrast, he viewed reduced-frequency denosumab as actionable now, concluding that every-12-week administration provides comparable protection from skeletal events with meaningful advantages for toxicity, cost, and patient convenience.
Speaker Disclosure Information: Dr Schwartzberg reported no relevant disclosures for this presentation.