Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

A randomized, double-blind, placebo-controlled investigation of BCc1 nanomedicine effect on survival and quality of life in metastatic and non-metastatic gastric cancer patients.

BACKGROUND: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. METHODS: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. RESULTS: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days [95% confidence interval (CI) 82.37-265.62]) than in placebo (62 days [95% CI 0-153.42]); hazard ratio (HR): 0.5 [95% CI 0.25-0.98; p = 0.046]. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days [95% CI 393.245-664.75]) than in placebo (345 days [95% CI 134.85-555.14]); HR: 0.324 [95% CI 0.97-1.07; p = 0.066]. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. CONCLUSION: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1.

Pharmaceutical and clinical studies of celecoxib topical hydrogel for management of chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) can be categorized as a frequent dose-limiting side effect following administration of chemotherapeutic agents, which needs an effective medication to avoid dose reduction or discontinuation. Oral celecoxib has been proved to be the best pharmacological intervention to ameliorate the skin lesions. However, due to reported gastrointestinal and cardiovascular toxicity following its long-term administration, celecoxib topical application would be a safe alternative for skin disorders. In this work, first, we formulated and optimized a topical hydrogel of celecoxib (1%) and then we investigated its efficacy in the management of chemotherapy-induced HFS in cancer patients. Optimized hydrogel showed acceptable results for drug content, pH, rheology, and stability. Analyzing in vitro drug release study by various mathematical models, the optimized hydrogel showed a zero-order release pattern with 93.27 ± 1.56% cumulative celecoxib release within 8 h. Ex vivo permeation studies across Wistar rat skin indicated suitable skin retention of celecoxib for topical delivery. Twenty-nine patients suffering from HFS were randomized to receive celecoxib and the placebo hydrogels 2 times a day for 3 weeks. At the baseline and at the end of the trial, HFS grades were determined. No serious adverse events occurred in patients who completely followed the instructions. No statistically significant differences between two arms were observed at the baseline (p value = 0.38). By contrast, Wilcoxon signed-rank test showed significant differences when secondary grades (p value = 0.05) and grade differences (p values < 0.001) were analyzed. Overall, the study proved that celecoxib hydrogel could be a promising intervention to manage HFS side effect.