QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial.

BACKGROUND: This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative. METHODS: Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32. RESULTS: Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups. CONCLUSIONS: QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer. TRIAL REGISTRATION: Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

Real-world treatment patterns and outcomes of pyrotinib-based therapy in patients with HER2-positive advanced breast cancer (PRETTY): A nationwide, prospective, observational study.

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential.

DFusion: Denoised TSDF Fusion of Multiple Depth Maps with Sensor Pose Noises.

The truncated signed distance function (TSDF) fusion is one of the key operations in the 3D reconstruction process. However, existing TSDF fusion methods usually suffer from the inevitable sensor noises. In this paper, we propose a new TSDF fusion network, named DFusion, to minimize the influences from the two most common sensor noises, i.e., depth noises and pose noises. To the best of our knowledge, this is the first depth fusion for resolving both depth noises and pose noises. DFusion consists of a fusion module, which fuses depth maps together and generates a TSDF volume, as well as the following denoising module, which takes the TSDF volume as the input and removes both depth noises and pose noises. To utilize the 3D structural information of the TSDF volume, 3D convolutional layers are used in the encoder and decoder parts of the denoising module. In addition, a specially-designed loss function is adopted to improve the fusion performance in object and surface regions. The experiments are conducted on a synthetic dataset as well as a real-scene dataset. The results prove that our method outperforms existing methods.

miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression.

Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC.