Data presented at the European Society for Medical Oncology (ESMO) 2018 Congress, held October 19 – 23, 2018 in Munich, Germany and simultaneously published in the New England Journal of Medicine (NEJM) on October 20, 2018, confirms the positive results from the Phase III IMpassion130 study of atezolizumab (MPDL3280A; Tecentriq?; Genentech/Roche), an engineered anti-PD-L1 antibody, plus nab-paclitaxel (albumin-bound paclitaxel; Abraxane?; Abraxis Bioscience, a wholly owned subsidiary of Celgene Corporation) for the initial (first-line) treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC).
Breast cancer is the most common cancer among women worldwide.
According to the American Cancer Society, approximately 269,000 people in the United States will be diagnosed with breast cancer, and more than 41,000 will die from the disease in 2018. Breast cancer is not one, but many diseases based on the biology of each tumor. For example, in triple-negative breast cancer, tumor cells lack hormone receptors and do not have excess HER2 protein. Approximately 15% of breast cancers are triple-negative based on the results of diagnostic tests. mTNBC is an aggressive form of the disease with only a few treatment options.
One of the potential treatment options is atezolizumab. This novel agent is designed to bind with a protein called PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the re-activation of T cells.
The IMpassion130 study (NCT02425891) is a Phase III, multicenter, randomized, double-blind study evaluating the efficacy, safety and pharmacokinetics of atezolizumab plus nab-paclitaxel compared with placebo plus nab-paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer.
The study enrolled 902 people who were randomized equally (1:1).
The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS. PFS and OS were assessed in all randomized patients (ITT) and in the PD-L1-positive population. Secondary endpoints include objective response rate (ORR), duration of response and time to deterioration in Global Health Status/Health-Related Quality of Life.
The combination of atezolizumab and chemotherapy significantly reduced the risk of disease worsening or death (progression-free survival; PFS) compared with chemotherapy alone in all randomized patients (intention-to-treat; ITT) (median PFS=7.2 vs. 5.5 months; hazard ratio [HR]=0.80, 95% CI: 0.69-0.92, p=0.0025) and the PD-L1-positive population (median PFS=7.5 vs. 5.0 months; HR=0.62, 95% CI: 0.49-0.78, p<0.0001), a subgroup determined by PD-L1 biomarker testing.
At this interim analysis, statistical significance was not met for overall survival (OS) in the ITT population (median OS=21.3 vs. 17.6 months; HR=0.84, 95% CI: 0.69-1.02, p=0.0840), but showed a clinically meaningful 9.5-month OS improvement in the PD-L1-positive population (median OS=25.0 vs. 15.5 months; HR=0.62, 95% CI: 0.45-0.86). Due to the hierarchical statistical design, results in the PD-L1-positive population were not formally tested. Follow-up will continue until the next planned analysis.
Safety in the atezolizumab plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.
?These important results in people with metastatic triple-negative breast cancer whose disease expresses the PD-L1 protein are highly encouraging and represent a significant step forward in the treatment of this challenging disease,? noted Sandra Horning, M.D., chief medical officer and head of Global Product Development.
?We have shared the IMpassion130 results with global health authorities with the hope of bringing this [atezolizumab] combination to people with PD-L1-positive, metastatic triple-negative breast cancer as soon as possible.?
Currently, Genentech has seven ongoing Phase III studies investigating atezolizumab in TNBC, including early and advanced stages of the disease.
The nature and incidence of severe adverse events (SAEs) and Grade 3-4 adverse events (AEs) were consistent with the known safety profile of the individual study drugs or the underlying disease.
Severe adverse events were reported in 23% of people receiving atezolizumab plus nab-paclitaxel compared to 18% of people receiving chemotherapy alone.
SAEs occurring in one percent or more of people receiving atezolizumab plus nab-paclitaxel were pneumonia (2%), urinary tract infection (1%), dyspnea (difficulty breathing; 1%) and pyrexia (fever; 1%).
Grade 3-4 adverse events were reported in 49% of people receiving atezolizumab plus nab-paclitaxel compared to 42% of people receiving chemotherapy alone. The most common Grade 3-4 adverse event in people receiving atezolizumab plus nab-paclitaxel were an abnormal low count of neutropenia (a certain type of white blood cell; 8%); decreased neutrophil count (5%); peripheral neuropathy (numbness, tingling or pain in the hands or feet; 6%); fatigue (4%); and anemia (decrease in red blood cells; 3%).
Peripheral neuropathy was the only Grade 3-4 adverse event reported with a two percent or higher incidence in people receiving atezolizumab plus nab-paclitaxel compared to people receiving chemotherapy alone (6% vs. 3%).
 A Study of Atezolizumab in Combination With Nab-Paclitaxel Compared With Placebo With Nab-Paclitaxel for Participants With Previously Untreated Metastatic Triple-Negative Breast Cancer (IMpassion130) | NCT02425891
 TECENTRIQ? (atezolizumab) injection, for intravenous use | Initial U.S. Approval: 2016
 TECENTRIQ? (atezolizumab) Summary of Product Characteristics | EMA | Date of first authorization: 21 September 2017
Last Editorial Review: October 20, 2018
Featured Image: ESMO 2018 Congress | October 19 – 23, 2018, Munich, Germany . Courtesy: ? 2018 European Society for Medical Oncology | ESMO. Used with permission.
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