Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Brigham and Women's Hospital, director of surgical research, director of Breast Immuno-Oncology Program, and co-director of the Breast Cancer Clinical Research Program at Dana-Farber Cancer Institute, discusses patient-reported quality of life (QoL) associated with neoadjuvant atezolizumab (Tecentriq) plus chemotherapy in early triple-negative breast cancer (TNBC).

The patients-reported outcomes from the phase 3 IMpassion031 study (NCT03197935) helped to clarify the QoL for those undergoing treatment with the atezolizumab/chemotherapy regimen, says Mittendorf. 

Importantly, when examining domains detailed in the report, such as treatment-related symptoms, symptom bother, role function, physical function, emotional and social function, and health-related quality of life, a decrease in baseline QoL was observed; however, this increased again as patients completed treatment, adds Mittendorf.

This appears to be comparable in both arms of the trial, which may indicate that patients who received the immunotherapy agent did not experience a significant decrease in QoL, concludes Mittendorf.

Videos

Elizabeth A. Mittendorf, MD, PhD, discusses patient-reported quality of life associated with neoadjuvant atezolizumab plus chemotherapy in early triple-negative breast cancer.

Dr. Mittendorf on QoL With Neoadjuvant Atezolizumab/Chemo in Early TNBC

Elizabeth A. Mittendorf, MD, PhD, director of the Breast Immuno-Oncology Program at Dana-Farber/Brigham and Women's Cancer Center, discusses the frontline approval of atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) in patients with locally advanced or metastatic PD-L1-positive triple-negative breast cancer.

This anticipated approval is based on findings from the phase III IMpassion130 trial, in which the addition of atezolizumab to nab-paclitaxel led to a 40% reduction in the risk of progression or death compared with nab-paclitaxel alone in this patient population. The coprimary endpoints were progression-free and overall survival (OS).

When the data were presented and published, Mittendorf notes that there was a statistically significant improvement in PFS, which was most pronounced in patients who were PD-L1 positive. Additionally, an interim analysis of OS showed that, in the intent-to-treat population, although that there was a benefit with the combination, it was not found to be statistically significant. However, the OS benefit increased to 25 months in the PD-L1-positive population, which Mittendorf said garnered enthusiasm among physicians and patients.

Although this marks a tremendous advance in TNBC treatment, she adds that it now needs to be determined which patients will not respond to this regimen, or which patients initially respond and then progress on treatment. This approval will continue the enthusiasm for immunotherapy research in other breast cancer subtypes, she concludes.

Elizabeth A. Mittendorf, MD, PhD, director of the Breast Immuno-Oncology Program at Dana-Farber/Brigham and Women's Cancer Center, discusses the frontline approval of atezolizumab in combination with nab-paclitaxel in patients with locally advanced or metastatic PD-L1

Dr. Mittendorf on FDA Approval of Frontline Atezolizumab/Nab-Paclitaxel in PD-L1+ TNBC

Elizabeth A. Mittendorf, MD, PhD, Robert and Karen Hale Distinguished Chair in Surgical Oncology, director, Breast Immuno-Oncology Program, Director of Research, Breast Surgical Oncology, Dana-Farber/Brigham and Women’s Cancer Center, discusses immunotherapy efforts in breast cancer.

Mittendorf says that there is some interesting neoantigen work being done at Dana-Farber Cancer Institute, specifically antigen discovery. The goal of antigen discovery is to identify targets for vaccination.

Another area of interest is evaluating the impact of current standard therapies for breast cancer on the immune microenvironment. This is work that Mittendorf plans to continue with the help of collaborators and new technology. Research will focus on both lymphoid and myeloid cells, Mittendorf says.

Elizabeth A. Mittendorf, MD, PhD, Robert and Karen Hale Distinguished Chair in Surgical Oncology, director, Breast Immuno-Oncology Program, Director of Research, Breast Surgical Oncology, Dana-Farber/Brigham and Women’s Cancer Center, discusses immunotherapy efforts in breast cancer.
 

Dr. Mittendorf Discusses Immunotherapy Efforts in Breast Cancer

Elizabeth A. Mittendorf, MD, PhD, associate professor in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center, discusses the impact of pertuzumab (Perjeta) on the treatment landscape of HER2-positive breast cancer.

In December 2017, the FDA approved pertuzumab in combination with trastuzumab (Herceptin) and chemotherapy as an adjuvant treatment for patients with HER2-positive breast cancer, based on the results from the APHINITY trial.

In the phase III trial, adjuvant treatment with pertuzumab, trastuzumab, and chemotherapy demonstrated a 3-year invasive disease-free survival (iDFS) rate of 94.1% versus 93.2% for those who received trastuzumab plus chemotherapy and placebo. This represented an 18% reduction in the risk of developing invasive disease or death (HR, 0.82; 95% CI, 0.67-1.00,

 = .047). The 4-year iDFS rates were 92.3% versus 90.6%, respectively.

The most common grade 3/4 adverse events (AEs) in the pertuzumab and placebo groups, respectively, were neutropenia (16% vs 16%), febrile neutropenia (12% vs 11%), diarrhea (10% vs 4%), and anemia (7% vs 5%). Fatal AEs occurred in 0.8% of patients in each group. AEs led to dose discontinuations for 7.3% of patients in the pertuzumab group versus 6.4% with placebo.

APHINITY is getting a lot of attention, but neratinib (Nerlynx) has also been approved, making the HER2-positive setting more interesting and exciting, explains Mittendorf.

Dr. Mittendorf on the Impact of Pertuzumab in HER2+ Breast Cancer

Elizabeth A. Mittendorf, MD, PhD, associate professor, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, discusses a clinical trial examining nelipepimut-S plus GM-CSF vaccine therapy as a treatment for patients with breast cancer.

This HER2-derived peptide vaccine is immunogeneic and aimed to prevent disease recurrence, explains Mittendorf. In combination with GM-CSF, the strategy is to inoculate patients who are rendered disease-free with their standard therapy. The goal is to stimulate an immune response to help prevent recurrence.

Earlier phase studies show that the vaccine strategy has decreased recurrence rates by approximately 50%. This could potentially lead to an FDA approval of the combination.

View more from the 33rd Annual Miami Breast Cancer Conference

Elizabeth A. Mittendorf, MD, PhD,  associate professor, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, discusses a clinical trial examining nelipepimut-S plus GM-CSF vaccine therapy as a treatment for patients with breast cancer. 

Dr. Mittendorf on Nelipepimut-S Plus GM-CSF in Breast Cancer

Elizabeth A. Mittendorf, MD, PhD, associate professor, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, discusses nelipepimut-S (NeuVax) and a proposed trial for patients with ductal carcinoma in situ (DCIS).

Mittendorf has been involved with the development of nelipepimut-S, an immunodominant nonapeptide that will now be examined in the phase III PRESENT trial for patients with low to intermediate HER2 expression.

Nelipepimut-S was also tested in phase I/II studies and was found to be safe and effective, eliciting an immune response, Mittendorf explains. The vaccine was administered to patients with breast cancer who were found to be disease-free with standard of care therapy, with a purpose to prevent disease recurrence. Enrolled patients, who were at a 20% risk of disease recurrence, were at a 10% risk following treatment with nelipepimut-S.

A proposed trial will examine nelipepimut-S in the adjuvant setting for patients with DCIS. Patients will be vaccinated prior to surgery, and a blood test will determine if patients have an appropriate immune response, Mittendorf says.

View more from the 2015 AACR Annual Meeting

Elizabeth A. Mittendorf, MD, PhD, associate professor, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, discusses nelipepimut-S (NeuVax) and a proposed trial for patients with ductal carcinoma in situ (DCIS).  

Elizabeth A. Mittendorf, MD, PhD

Articles

Dr. Mittendorf on QoL With Neoadjuvant Atezolizumab/Chemo in Early TNBC

Dr. Mittendorf on FDA Approval of Frontline Atezolizumab/Nab-Paclitaxel in PD-L1+ TNBC

Dr. Mittendorf Discusses Immunotherapy Efforts in Breast Cancer

Dr. Mittendorf on the Impact of Pertuzumab in HER2+ Breast Cancer

Dr. Mittendorf on Nelipepimut-S Plus GM-CSF in Breast Cancer

Dr. Mittendorf on Nelipepimut-S in Breast Cancer