Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer

Abstract

Therapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).

Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer

“…The mOS was 19.2 months in the atezolizumab group vs . 22.8 months in the placebo group; this clinical activity was consistent with that in another clinical trial (paclitaxel as the backbone of chemotherapy plus durvalumab) showing an mPFS and mOS of 5.0 and 20.7 months, respectively ( 35 ). In IMpassion131, paclitaxel was probably chosen as the backbone of chemotherapy and a steroid was administered together with paclitaxel during chemotherapy, leading to the limited therapeutic effect of atezolizumab.…”

Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis

“…Paclitaxel (PR) is one of the active chemotherapeutic drugs commonly used to treat metastatic breast cancer [ 8 , 9 ]. Paclitaxel, a class of taxanes, is an anti-tumor drug that binds to β-tubulin and prevents mitosis through microtubule hyperstabilization [ 9 ].…”

“…Chemotherapy has generally been regarded as a standard treatment even if the disease is operable [ 6 ]. The most commonly used anti-cancer drugs for breast cancer are tamoxifen (Nolvadex), doxorubicin (Adriamycin), and paclitaxel (Taxol) [ 7 , 8 , 9 , 10 ]. However, as previously mentioned, chemoresistance that occurs through alteration to drug targets by either innate or acquired abilities has emerged as a major issue that limits the chemotherapy for cancer patients [ 11 ].…”

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice

“…Despite the paucity of participants (n = 24), encouraging a results have been registered in a small phase I/II single arm trial (NCT02628132) evaluating the safety and the efficacy of durvalumab in combination with paclitaxel (5 and 20.7 months for the PFS and OS, respectively) [85].…”