FDA Approval Summary: Atezolizumab Plus Paclitaxel Protein-bound for the Treatment of Patients with Advanced or Metastatic TNBC Whose Tumors Express PD-L1

Abstract

On March 8, 2019, the FDA granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 [PD-L1 stained tumor-infiltrating immune cells (IC) of any intensity covering ≥1% of the tumor area], as determined by an FDA-approved test. Approval was based on data from IMpassion130, which randomized patients to receive atezolizumab or placebo in combination with paclitaxel protein-bound. Investigator-assessed progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1-positive populations were coprimary endpoints. After 13-month median follow-up, the estimated median PFS in the PD-L1-positive population was 7.4 months in the atezolizumab arm and 4.8 months in the placebo arm [HR ¼ 0.60; 95% confidence interval (CI), 0.48-0.77]. Overall survival (OS) results were immature with 43% deaths in the ITT population, representing 59% of the OS events required to perform the final OS analysis. Adverse reactions occurring in ≥20% of patients receiving atezolizumab with paclitaxel protein-bound were alopecia, peripheral neuropathies, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite. Accelerated approval was appropriate taking into account the unmet medical need along with the immaturity of the OS results and potential for PFS in the PD-L1-expressing population to predict clinical benefit.

Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring

“…The prognosis of triple negative breast cancer (TNBC) remains poor, and due to a lack of targetable biomarkers, chemotherapy is the only systemic therapy widely available ( Waks and Winer, 2019 ). Recently, atezolizumab with nab-Paclitaxel was approved as a combinatorial therapeutic for metastatic TNBC for a subpopulation of programed cell death ligand 1 (PD-L1)-positive patients with advanced metastatic breast cancer ( Heimes and Schmidt, 2019 ; Narayan et al, 2020 ; Reddy et al, 2020 ). However, chemotherapeutic agents are often associated with a relatively low response rate ( Lebert et al, 2018 ) and adverse side effects, such as cardiotoxicity in the case of Dox ( Zhao et al, 2018 ; Cranmer, 2019 ; Zhang et al, 2020 ).…”

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

“…The programmed cell death-1 (PD-1) signal pathway has a ligand called 1 (PD-L1) [223]; both can lead to programmed death on malignant cells [224], especially for TNBC [225]. Atezolizumab helps in the therapeutics in TNBC patients with advanced or metastatic cancer [226]. Nevertheless, in order to prevent disease progression or avoid side effects such as alopecia, thrombocytopenia, anemia and neutropenia, the FDA recommends atezolizumab dose is 840 mg intravenous (IV) infusion over 60 min, followed by 100 mg/m 2 paclitaxel for 28-day cycle.…”

Quantifying PD-L1 Expression to Monitor Immune Checkpoint Therapy: Opportunities and Challenges

“…To date, all approved PD-L1 drugs have been mAbs. Atezolizumab (non-glycosylated IgG1κ, t 1/2 27 d) is approved for liver cancer [160], metastatic NSCLC [2], extensive stage small-cell lung cancer, metastatic TNBC [161] and advanced urothelial cancers [162]. Avelumab (IgG1λ, t 1/2 6.1 d) is approved to treat metastatic Merkel-cell carcinoma [163] and advanced or metastatic urothelial carcinoma [164].…”