Late-Breaking Breast Cancer Data at ESMO 2026 Highlight ADCs and Ribociclib

Five phase 3 analyses presented as late-breaking abstracts at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid reported progression-free survival (PFS) improvements with 3 antibody-drug conjugates (ADCs) in advanced breast cancer, a 6-year overall survival (OS) benefit with adjuvant ribociclib (Kisqali) in early breast cancer, and a PFS gain without an OS difference for pembrolizumab (Keytruda) plus chemotherapy.¹⁻⁵

In each of the 3 ADC trials, led by investigators in China, median PFS more than doubled vs physician’s choice of chemotherapy while OS data remained immature.¹⁻³

Trastuzumab Rezetecan Improves PFS in HER2-Low Disease

In the open-label phase 3 HORIZON-Breast06 trial (NCT05814354), 551 patients with HER2-low advanced breast cancer and no more than 1 prior line of chemotherapy for metastatic disease were randomly assigned 1:1 to trastuzumab rezetecan (SHR-A1811), a HER2-directed ADC, at 6.4 mg/kg every 3 weeks (n = 277) or physician’s choice of chemotherapy (n = 274; taxanes, eribulin, capecitabine, or gemcitabine).¹ Overall, 81.5% were chemotherapy-naive for metastatic disease, 73.0% had hormone receptor–positive disease, and 64.8% had received a prior CDK4/6 inhibitor.

The coprimary end points were PFS by blinded independent central review (BICR) in chemotherapy-naive patients and in the overall population. At a median follow-up of 18.0 months, median PFS in chemotherapy-naive patients was 16.6 vs 6.8 months (HR, 0.25; 95% CI, 0.19-0.33; P < .0001). In the overall population, median PFS was 16.4 vs 6.8 months (HR, 0.27; 95% CI, 0.21-0.34; P < .0001).

The benefit was consistent across prespecified subgroups, including hormone receptor–negative disease (16.5 vs 6.8 months; HR, 0.34) and hormone receptor–positive disease (16.4 vs 6.7 months; HR, 0.24). The objective response rate (ORR) was 75.5% vs 41.2%. OS was immature, with 66 events (23.8%) vs 77 events (28.1%). Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 84.1% vs 67.9% of patients, and interstitial lung disease (ILD) occurred in 7 patients (2.5%) receiving trastuzumab rezetecan.

TQB2102 Extends PFS in HER2-Low Disease

In the phase 3 APEX-Breast01 trial (NCT06561607), 543 patients with HER2-low (IHC 1+ or 2+/ISH–) recurrent or metastatic breast cancer and no prior chemotherapy for advanced disease were randomly assigned 1:1 to TQB2102, a biparatopic HER2-targeting ADC, at 7.5 mg/kg every 3 weeks (n = 269) or physician’s choice of capecitabine, paclitaxel, or nab-paclitaxel (n = 274).² Most patients (n = 461) had hormone receptor–positive disease and had progressed after endocrine therapy; 91.3% had received a prior CDK4/6 inhibitor. The primary end point was BICR-assessed PFS in hormone receptor–positive/HER2-low patients.

At the interim analysis (data cutoff, May 31, 2026), median PFS in hormone receptor–positive/HER2-low patients was 16.4 vs 5.5 months (HR, 0.29; 95% CI, 0.22-0.39; P < .0001), with the same medians and HR in all patients with HER2-low disease. In the 82 patients with hormone receptor–negative disease, median PFS was 8.5 vs 5.4 months (HR, 0.27; 95% CI, 0.13-0.56).

OS data were immature, with HRs of 0.47 (95% CI, 0.26-0.87) in hormone receptor–positive patients and 0.44 (95% CI, 0.25-0.79) in all patients with HER2-low disease. The most common grade 3 or higher TRAEs were decreased neutrophil count (30.1% vs 23.3%) and decreased white blood cell count (21.6% vs 14.0%). TRAEs led to discontinuation in 1.5% of patients in each arm, and TQB2102-related ILD occurred in 6 patients (2.2%; grade 3, 1.1%).

Iza-Bren Improves PFS After Endocrine Therapy and Chemotherapy

In the phase 3 PANKU-Breast01 trial (NCT06343948), 383 patients with unresectable locally advanced or metastatic hormone receptor–positive/HER2-negative breast cancer were randomly assigned and treated with izalontamab brengitecan (iza-bren), a first-in-class bispecific ADC targeting EGFR and HER3, at 2.5 mg/kg on days 1 and 8 every 3 weeks (n = 190) or physician’s choice of eribulin, capecitabine, gemcitabine, or vinorelbine (n = 193).³ All had progressed after at least 1 line of endocrine therapy and 1 or 2 lines of chemotherapy and had previously received CDK4/6 inhibitors and taxanes.

At the prespecified final PFS analysis (data cutoff, July 21, 2026), median PFS by BICR was 8.18 vs 4.01 months (HR, 0.41; 95% CI, 0.33-0.53; P < .0001). The confirmed ORR was 40.5% vs 20.2%, and median duration of response was 6.93 vs 4.21 months. OS was immature, with no detrimental effect observed. Grade 3 or higher TRAEs were predominantly hematologic, 1.6% of patients discontinued iza-bren because of TRAEs, and adjudicated ILD occurred in 2 patients (1.1%; grade 1 or 2).

Adjuvant Ribociclib Shows Sustained iDFS and OS Benefit

In the phase 3 NATALEE trial (NCT03701334), patients with hormone receptor–positive/HER2-negative stage II or III early breast cancer were randomly assigned 1:1 to 3 years of ribociclib 400 mg daily (3 weeks on, 1 week off) plus a nonsteroidal aromatase inhibitor (NSAI) for 5 years, or NSAI alone.⁴ The FDA approved ribociclib with an aromatase inhibitor for high-risk early breast cancer in 2024, and a 5-year analysis presented at the 2025 ESMO Congress showed an invasive disease–free survival (iDFS) HR of 0.716 (95% CI, 0.618-0.829).⁶

At the May 15, 2026, data cutoff, all patients had been off ribociclib for a median of 38 months. With a median OS follow-up of 66.5 months, ribociclib plus NSAI reduced the risk of death vs NSAI alone (HR, 0.809; 95% CI, 0.661-0.989; nominal 1-sided P = .019). The absolute OS benefit increased from 1.2% at 5 years (93.89% vs 92.73%) to 2.1% at 6 years (91.86% vs 89.73%) and was consistent across key subgroups. Breast cancer–specific survival was supportive (HR, 0.706; 95% CI, 0.559-0.890).

At a median iDFS follow-up of 66.3 months, the iDFS benefit persisted (HR, 0.741; 95% CI, 0.646-0.849; nominal 1-sided P < .0001), with the absolute benefit growing from 4.1% at 5 years (85.32% vs 81.24%) to 5.3% at 6 years (83.23% vs 77.92%). Distant disease–free survival (HR, 0.744) and distant recurrence–free survival (HR, 0.738) benefits were maintained, and no new safety signals were observed.

Pembrolizumab Plus Chemotherapy Improves PFS but Not OS

In the phase 3 KEYNOTE-B49 trial (NCT04895358), 342 patients with locally recurrent inoperable or metastatic hormone receptor–positive/HER2-negative breast cancer, a PD-L1 combined positive score (CPS) of 1 or higher, and prior endocrine therapy who were candidates for first-line chemotherapy were randomly assigned to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus chemotherapy (paclitaxel, nab-paclitaxel, liposomal doxorubicin, or capecitabine).⁵ The sample size was reduced after a protocol amendment because of low PD-L1 prevalence, and nearly all patients had prior CDK4/6 inhibitor exposure.

The primary end point was BICR-assessed PFS in patients with a CPS of 1 or higher. At the primary analysis (data cutoff, September 22, 2025), median PFS was 6.7 vs 6.0 months (HR, 0.74; 95% CI, 0.58-0.95; P = .0089). In patients with a CPS of 10 or higher, the PFS HR was 0.59 (95% CI, 0.35-0.98).

At the final analysis (data cutoff, March 16, 2026; median follow-up, 34.9 months), the PFS benefit was maintained (HR, 0.74; 95% CI, 0.58-0.95), but OS did not differ significantly (median, 21.0 vs 22.2 months; HR, 1.04; 95% CI, 0.81-1.33; P = .6185). Grade 3 or higher TRAEs occurred in 37.6% vs 32.7% of patients, and 11.2% vs 5.4% discontinued treatment because of TRAEs.

REFERENCES

1. Fan Y, Liu Y, Wang Y, et al. Trastuzumab rezetecan (SHR-A1811) in HER2-low advanced breast cancer (BC): a randomized phase 3 study (HORIZON-Breast06). Presented at: 2026 ESMO Congress; October 23-27; Madrid, Spain. Abstract LBA13.

2. Wang S, Zhang Q, Shi Y, et al. APEX-Breast01: TQB2102 vs chemotherapy in HER2-low recurrent or metastatic breast cancer (r/m BC) - results from a randomized phase 3 study. Presented at: 2026 ESMO Congress; October 23-27; Madrid, Spain. Abstract LBA27.

3. Lan B, Shi Y, Shao X, et al. PANKU-Breast01: randomized phase 3 study of izalontamab brengitecan (iza-bren) in previously treated unresectable locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Presented at: 2026 ESMO Congress; October 23-27; Madrid, Spain. Abstract LBA50.

4. Slamon DJ, Hortobagyi GN, Stroyakovskiy D, et al. Adjuvant ribociclib + nonsteroidal aromatase inhibitor in patients with HR+/HER2- early breast cancer: NATALEE 6-y overall survival and efficacy outcomes. Presented at: 2026 ESMO Congress; October 23-27; Madrid, Spain. Abstract LBA25.

5. Rugo HS, Kok M, Gonçalves A, et al. Results from KEYNOTE-B49: a phase 3, randomized, double-blind study of pembrolizumab vs placebo plus chemotherapy in HR+/HER2- advanced breast cancer. Presented at: 2026 ESMO Congress; October 23-27; Madrid, Spain. Abstract LBA51.

6. Crown J, Stroyakovskii D, Yardley D, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR+/HER2– early breast cancer: NATALEE 5-year outcomes. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA14.