Atezolizumab May Help Combat Some Breast Cancers

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Atezolizumab was approved for treating patients with metastatic non–small-cell lung cancer who experienced disease progression during or following platinum-containing chemotherapy. Now, it turns out this agent may have a role in combating breast cancer.

Recently, atezolizumab was approved for treating patients with metastatic non–small-cell lung cancer (NSCLC) who experienced disease progression during or following platinum-containing chemotherapy. Now, it turns out this agent may have a role in combating breast cancer.

Researchers at Fox Chase Cancer Center in Philadelphia are beginning a phase II immunotherapy clinical trial for newly diagnosed, locally recurrent, or metastatic human epidermal growth factor receptor (HER2)-overexpressing breast cancer. The investigators are hoping to learn how this anti-programmed death ligand 1 (anti-PD-L1) immunotherapy agent works when used in combination with the standard of care regimen of paclitaxel, pertuzumab, and trastuzumab.

The clinical trial will study both the safety and efficacy of the drug combination in treating HER2-overexpressing breast cancer. The team will also examine biomarkers to better understand how effective this combination may be at attacking the cancer on a molecular level.

“The study is planned to enroll 50 patients in four national cancer centers in the US. We expect to have our results in 2 years. Our results are expected to lead into a randomized phase III clinical trial looking at the efficacy of adding immune checkpoint inhibition to standard of care HER2-targeting regimen for metastatic HER2-overexpressing breast cancer to potentially improve outcomes for patients with HER2-positive breast cancer,” study investigator Lori Goldstein, MD, who is a medical oncologist at Fox Chase Cancer Center, told OncoTherapy Network.

The US Food and Drug Administration (FDA) on October 18, 2016, approved atezolizumab for patients with metastatic NSCLC. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinas (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. Atezolizumab prior to this approval had received FDA accelerated approval for the treatment of locally advanced or metastatic urothelial carcinoma that progresses after platinum-containing chemotherapy.

The approval of this agent for NSCLC patients was based on two international, randomized, open-label clinical trials (OAK and POPLAR) that demonstrated consistent results in efficacy and safety in a total of 1,137 patients with NSCLC. The median overall survival (OS) in the OAK trial was 13.8 months in the atezolizumab arm compared to 9.6 months in the docetaxel arm. The median OS in the POPLAR trial was 12.6 months for the atezolizumab arm and 9.7 for docetaxel arm.

The most common adverse reactions in the primary safety analysis population (POPLAR trial) in patients treated with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. The most common grade 3/4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included pneumonitis, hepatitis, colitis, and thyroid disease.

On May 9, 2017, Genentech announced that the phase III IMvigor211 study that evaluated atezolizumab in patients with locally advanced or metastatic urothelial cancer whose disease progressed during or after treatment with a platinum-based chemotherapy did not meet its primary endpoint of OS compared to chemotherapy. Chief medical officer and head of Global Product Development for Genentech Sandra Horning, MD, said these results were not what the company had been expecting. However, she said Genentech believes that this agent will continue to play an important role in the treatment of people with advanced bladder cancer. 

The atezolizumab breast cancer trial at Fox Chase will open to enrollment soon.

                                                        

 

 

 

 

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