Nusayba Bagegni, MD, assistant professor of medicine, Division of Medical Oncology, Washington University School of Medicine, medical oncologist, Siteman Cancer Center, discusses the prevalence of interstitial lung disease (ILD) in patients with HER2-positive breast cancer treated with fam-trastuzumab deruxtecan-nxki (Enhertu).

Although trastuzumab deruxtecan has been a transformative treatment option approved for select patients with metastatic HER2-positive and HER2-low breast cancer, ILD is a toxicity linked with the antibody-drug conjugate (ADC).

Bagegni notes that she has treated patients who have developed grade 1 ILD following treatment with trastuzumab deruxtecan. These patients received routine scans that detected ground-glass opacities, and in these cases, trastuzumab deruxtecan needed to be interrupted. Patients with grade 1 ILD may also be offered corticosteroids, Bagegni says.

Trastuzumab deruxtecan should be stopped for symptomatic patients with ILD, and they should also receive corticosteroids immediately, Bagegni explains. These patients should also be examined by a pulmonologist, who can conduct pulmonary function tests and evaluate for infectious disease, Bagegni adds.

In her experience managing patients with grade 1 ILD, Bagegni says a chest computed tomography (CT) scan approximately 4 weeks following the onset of toxicity is used to reassess the ILD and determine if the patient can resume treatment with trastuzumab deruxtecan. However, in symptomatic patients with grade 2 or higher ILD, if the adverse effect is determined to be related to trastuzumab deruxtecan, it is recommended that those patients discontinue therapy with the ADC, Bagegni explains. More investigations are needed to better understand which patients are at a higher risk for ILD and which patients could potentially be rechallenged with trastuzumab deruxtecan, Bagegni concluded.

Videos

Nusayba Bagegni, MD, discusses the prevalence of interstitial lung disease in patients with HER2-positive breast cancer treated with trastuzumab deruxtecan.

Dr Bagegni on the Prevalence of ILD With Trastuzumab Deruxtecan in HER2+ Breast Cancer

Nusayba Bagegni, MD, assistant professor of medicine, Division of Medical Oncology, Washington University School of Medicine, medical oncologist, Siteman Cancer Center, discusses updated efficacy and biomarker data from the phase 2 APT (NCT00542451) and ATEMPT (NCT01853748) trials in early-stage HER2-positive breast cancer.

The APT trial investigated the administration of adjuvant paclitaxel over the course of 3 months,followed by treatment with trastuzumab (Herceptin) for 9 months in patients with small, node-negative, HER2-positive breast cancer. According to the final 10-year analysis, the regimen produced an invasive disease-free survival (iDFS) rate of 91.3% and a recurrence-free interval (RFI) of 96.3%. Overall, the trial confirmed the regimen's ability to provide long-term survival benefit.

The ATEMPT trial compared the toxicity of ado-trastuzumab emtansine (Kadcyla; T-DM1) with adjuvant paclitaxel plus trastuzumab in patients with stage 1 HER2-positive breast cancer. In this trial, T-DM1 failed to demonstrate superior safety over the combination regimen. Alongside results from APT, these findings have solidified this regimen as the standard of care in stage I HER2-positive breast cancer.

Correlative analyses using the prognostic and predictive HER2DX assay were performed in both the APT and ATEMPT trials, Bagegni states. In the APT trial, HER2DX as a continuous variable was associated with a higher risk of disease recurrence. A HER2DX risk-score of 32 was identified as the optimal cutoff for low vs high risk status. Similarly, patients with HER2DX low-risk disease had a more favorable 5-year RFI and numerically improved 5-year DFS vs those with HER2DX high-risk disease. These data could be used to better predict patient benefit, Bagegni says. For example, patients who initially score worse may be eligible for more aggressive therapy in the future, while those who meet certain cutoffs for the HER2DX scoring system may have a better prognosis, Bagegni explains.

Moreover, PAM50 gene expression analysis indicated that patients with luminal B HER2-positive breast cancer are associated with worse disease-specific outcomes, Bagegni adds. Accordingly, future research efforts should focus on modifying approaches to treatment for this specific subgroup, Bagegni concludes.

: Dr. Bagegni reports receiving institutional research funding from Sermonix Pharmaceuticals, Inc, Xcovery Holding Company, LLC, Seattle Genetics, Inc, Ambrx, Inc, Novartis Pharmaceuticals Incorporation, Atossa Therapeutics, Inc, Daiichi Sankyo, AstraZeneca Pharmaceuticals LP, Pfizer Inc, Sarah Cannon Development Innovations, LLC

Nusayba Bagegni, MD, discusses updated efficacy and biomarker data from the phase 2 APT and ATEMPT trials in early-stage HER2-positive breast cancer.
 

Dr Bagegni on Updated APT and ATEMPT Results in Early-stage HER2+ Breast Cancer

Nusayba Bagegni, MD, assistant professor of medicine, Division of Medical Oncology, Washington University School of Medicine, medical oncologist, Siteman Cancer Center, discusses the safety profile of ado-trastuzumab emtansine (T-DM1; Kadcyla) in early-stage HER2-positive breast cancer.

In May 2019, the FDA approved T-DM1 for the adjuvant treatment of patients with early-stage HER2-positive disease who have residual invasive disease after neoadjuvant taxane and trastuzumab (Herceptin)-based therapy. 

Data from the phase 3 KATHERINE trial, which led to the regulatory decision, indicated that the toxicities with T-DM1 were similar to what has been observed in the metastatic space, says Bagegni. 

Specifically, T-DM1 can cause thrombocytopenia and neuropathy; however, these toxicities tended to be low grade in the KATHERINE trial, Bagegni explains.

Five cardiac events occurred in patients on the KATHERINE study, says Bagegni. Four of these events occurred in the trastuzumab group and 1 occurred in the T-DM1 group.

Radiation pneumonitis, which is a potentially concerning toxicity, was observed in 1.5% of patients treated with T-DM1 in the KATHERINE study, says Bagegni. 

Taken collectively, these results indicate that T-DM1 is an effective and well-tolerated option for this patient population.

Nusayba Bagegni, MD, discusses the safety profile of ado-trastuzumab emtansine in early-stage HER2-positive breast cancer.  



Nusayba Bagegni, MD

Articles

Dr Bagegni on the Prevalence of ILD With Trastuzumab Deruxtecan in HER2+ Breast Cancer

Dr Bagegni on Updated APT and ATEMPT Results in Early-stage HER2+ Breast Cancer

Dr. Bagegni on the Safety Profile of T-DM1 in Early-Stage HER2+ Breast Cancer