Analyzing Outcomes With T-DXd in HER2+ Breast Cancer With Brain Metastases

Dr Cortés on Analyzing Outcomes With T-DXd in HER2+ Breast Cancer With Brain Metastases

Javier Cortés, MD, PhD, head, International Breast Cancer Center, clinical investigator, Breast Cancer Research Program, Vall d’Hebron Institute of Oncology, discusses the rationale for analyzing outcomes with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive metastatic breast cancer who have brain metastases. Findings from this pooled analysis were presented at the 2023 ESMO Congress based on data derived from the phase 3 DESTINY-Breast01 (NCT03248492), DESTINY-Breast02 (NCT03523585), and DESTINY-Breast03 (NCT03529110) trials.

The efficacy of T-DXd in HER2-positive metastatic breast cancer is tempered by the prevalence of brain metastases, which can significantly impact patient outcomes, Cortés begins. To shed light on the potential of T-DXd in patients with HER2-positive metastatic breast cancer with either stable or unstable brain metastases, investigators delved into an exploration of this agent’s efficacy and role within the framework of the DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03 trials, he states. However, the variability in inclusion and exclusion criteria across these trials adds complexity to the understanding of these pooled analysis outcomes, Cortés explains.

DESTINY-Breast01 exclusively enrolled heavily pretreated patients who had previously received ado-trastuzumab emtansine (T-DM1; Kadcyla). In this single-arm trial, all patients received T-DXd. In DESTINY-Breast02, patients previously treated with T-DM1 were randomized to receive either T-DXd or physician's choice of therapy, Cortés notes. Finally, DESTINY-Breast03 included patients with a treatment history involving a taxane and trastuzumab (Herceptin), and randomly assigned patients to receive either T-DXd or T-DM1, he explains.

The pooled analysis considered the nuances between these trial designs, Cortés continues. Initially, DESTINY-Breast02 and DESTINY-Breast03 permitted limited numbers of patients with previously untreated and asymptomatic brain metastases, as did DESTINY-Breast01. However, amendments to the DESTINY-Breast02 and DESTINY-Breast03 enrollment criteria restricted the inclusion of patients with unstable brain metastases, he emphasizes. Although most patients enrolled in these trials exhibited stable brain metastases, a minority presented with unstable brain metastases, adding depth to the exploration of T-DXd's impact across different metastatic scenarios, Cortés concludes.

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Javier Cortés, MD, PhD, discusses the rationale for analyzing outcomes with trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer who have brain metastases.

Findings From a Pooled Analysis of Trastuzumab Deruxtecan in HER2+ Breast Cancer

Dr Cortés on Findings From a Pooled Analysis of Trastuzumab Deruxtecan in HER2+ Breast Cancer

Javier Cortés, MD, PhD, head, International Breast Cancer Center, clinical investigator, Breast Cancer Research Program, Vall d’Hebron Institute of Oncology, discusses primary outcomes and safety findings from a pooled analysis of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive metastatic breast cancer who have brain metastases. These data were derived from the phase 3 DESTINY-Breast01 (NCT03248492), DESTINY-Breast02 (NCT03523585), and DESTINY-Breast03 (NCT03529110) trials.

Findings from the pooled analysis were presented at the 2023 ESMO Congress and showed that T-DXd exhibited strong intracranial responses in patients with treated/stable and active brain metastases vs the comparator agents. In patients with stable brain metastases, T-DXd generated an intracranial objective response rate (IC-ORR) of 45.2%, along with a median intracranial duration of response (IC-DOR) of 12.3 months (range, 9.1-17.9), compared with 27.6% and 11.0 months (range, 5.6-16.0), respectively, in the comparator groups.

In patients with untreated or active brain metastases, T-DXd elicited an IC-ORR of 45.5% and a median IC-DOR of 17.5 months (range, 13.6-31.6) vs 12.0% and an undefined duration, respectively, in the comparator groups. Additionally, T-DXd yielded a numerically longer median central nervous system progression-free survival (CNS-PFS) in patients with both stable and active brain metastases and maintained an acceptable and manageable safety profile consistent with that seen in the overall patient population.

A total of 44 patients with untreated or active brain metastases received T-DXd, and 25 patients received the standard of care (SOC), Cortés begins. Conversely, 104 patients with stable or treated brain metastases received T-DXd, and 58 patients were treated with physician's choice of SOC, he explains. The IC-ORR and IC-DOR outcomes in these cohorts indicate T-DXd's superior activity vs SOC, Cortés emphasizes.

An exploratory CNS-PFS analysis conducted in the subgroup of patients with untreated active brain metastases demonstrated a median CNS-PFS of 4.0 months (95% CI, 2.7-5.7) with SOC vs18.5 months (95% CI, 13.6-23.3) with T-DXd, again emphasizing the activity of T-DXd in this patient group, Cortés continues. In terms of safety, adverse events (AEs) in patients with brain metastases were comparable with those observed in the overall population, with T-DXd–related serious treatment-emergent AEs reported in 13.0% of patients with brain metastases compared with 12.4% of patients in the overall population, respectively, he notes. Overall, T-DXd exhibited an acceptable and manageable safety profile in the overall population, with no significant differences in toxicity observed in patients with altered brain metastases, Cortés concludes.

Javier Cortés, MD, PhD, discusses primary outcomes and safety findings from a pooled analysis of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer who have brain metastases. 


Dr Cortés on Pooled Data for Trastuzumab Deruxtecan in HER2+ Breast Cancer With Brain Metastases

Javier Cortés, MD, PhD, head of breast cancer and gynecological cancers at Hospital Universitario Ramón y Cajal, as well as a clinical investigator in the breast cancer research program at Vall d’Hebron Institute of Oncology, discusses the incidence and management of male patients with breast cancer in Spain.

For every 100 women diagnosed with breast cancer in Spain, there is 1 man diagnosed, according to Cortés. Approximately 33,000 new cases of breast cancer are being diagnosed on an annual basis in the country and about 350 of them are male, Cortés adds.

Male and female patients receive similar treatments; however, if aromatase inhibitors are used in male patients, they must be combined with luteinizing hormone-releasing hormone analogues, according to Cortés. Overall treatment strategies should not differ greatly between male and female patients, Cortés concludes.

Javier Cortés, MD, PhD, discusses the incidence and management of male patients with breast cancer in Spain.

Dr. Cortés on the Incidence and Management of Male Breast Cancer in Spain

Javier Cortes, MD, PhD, head of breast cancer program at IOB Institute of Oncology, Madrid and Barcelona, discusses updated progression-free survival (PFS) data on the 

 with pembrolizumab plus chemotherapy in previously untreated patients with locally recurrent, inoperable or metastatic triple-negative breast cancer (TNBC).

, investigators presented the first co-primary end point of PFS and safety from the KEYNOTE-355 study, says Cortes. Firstly, in patients who are PD-L1—positive with a CPS score of ≥10, the primary end point was met with a hazard ratio (HR) of 0.65, which is both statistically significant and of great clinical importance, adds Cortes. The median PFS was 9.7 months with pembrolizumab and chemotherapy versus 5.6 months with placebo and chemotherapy (range, 0.49-0.86; 95% CI; 

Once this primary end point was achieved, investigators looked at the PFS data in patients with a CPS score of ≥1, adds Cortes. The trend was very clear, with a HR of 0.74; however, the 

value of 0.0014 did not reach statistical significance. The median PFS was 7.6 months in the pembrolizumab arm and 5.6 months in the placebo arm. The PFS data in the intent-to-treat population was not formally tested. Pembrolizumab plus chemotherapy improved PFS in patients with PD-L1—positive disease and a CPS score of ≥10 or more, concludes Cortes.

Javier Cortes, MD, PhD, discusses updated progression-free survival data from the phase 3 KEYNOTE-355 study with pembrolizumab plus chemotherapy in previously untreated patients with locally recurrent, inoperable or metastatic triple-negative breast cancer.

Javier Cortes, MD, PhD

Articles

Dr Cortés on Analyzing Outcomes With T-DXd in HER2+ Breast Cancer With Brain Metastases

Dr Cortés on Pooled Data for Trastuzumab Deruxtecan in HER2+ Breast Cancer With Brain Metastases

Dr. Cortés on the Incidence and Management of Male Breast Cancer in Spain

Dr. Cortes on Updated PFS Data From KEYNOTE-355 in PD-L1-High TNBC