ABSTRACT
OBJECTIVE: To establish clinical biosimilarity of BevaciRel™ bevacizumab biosimilar (study bevacizumab) with the reference innovator bevacizumab in terms of pharmacokinetics, efficacy, and safety in metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A total of 119 patients with mCRC were enrolled across 20 centers and randomized to receive study and reference bevacizumab in this Phase III clinical study. Of these, 116 patients were administered bevacizumab 5 mg/kg intravenously every 2 weeks with folinic acid, fluorouracil, and irinotecan regimen. The primary endpoint of the study was objective response rate (ORR) at week 25, and the secondary endpoints assessed were progression-free survival (PFS), overall survival (OS), and assessment of pharmacokinetics and safety along with immunogenicity in both treatment arms. RESULTS: The ORR was 60.53% in study bevacizumab and 66.67% in reference arm. The proportions of subjects showing CR and PR were comparable in both the arms. The median PFS at 1 year was 3.83 months in test arm and 4.6 months in reference arm. The mean OS was 10.91 months in test arm and 14.68 months in reference arm. The difference in ORR, median PFS, and OS was not statistically significant (P > 0.05). The median Tmaxwas 6.00 h in both the arms. The median t½ was 330.63 h and 226.14 h, respectively, for test and reference bevacizumab. The adverse event profile of both products was in line with the known profile of bevacizumab. CONCLUSION: The study biosimilar bevacizumab was found to be noninferior and clinically biosimilar to the reference bevacizumab, thereby meeting an unmet medical alternative need in mCRC.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab/administration & dosage , Biosimilar Pharmaceuticals/administration & dosage , Colorectal Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , Bevacizumab/adverse effects , Bevacizumab/pharmacokinetics , Biosimilar Pharmaceuticals/adverse effects , Biosimilar Pharmaceuticals/pharmacokinetics , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Capecitabine/administration & dosage , Capecitabine/adverse effects , Colorectal Neoplasms/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , India/epidemiology , Irinotecan , Male , Middle Aged , Neoplasm Metastasis , Treatment OutcomeABSTRACT
INTRODUCTION: The present study for biosimilar trastuzumab was a multicentric, randomized, two-arm parallel-group, comparative phase III study in patients with metastatic breast cancer. MATERIALS AND METHODS: Stage I of the study was conducted among 42 participants with equal distribution in the study and reference arm. After a loading dose of 8 mg/kg trastuzumab was administered intravenously on day 1 of the first cycle; serum samples were obtained at 0, 1.5 (end of IP infusion), 3, 6, 8, 24, 96, 168, and 336 h after the first infusion for the first cycle only. Cmax and AUC0-336 were calculated for a single dose. Stage II enrolled a total of 106 patients across 20 centers who were randomized to receive biosimilar trastuzumab (study trastuzumab) or the reference trastuzumab with paclitaxel. The primary endpoint of the objective response rate (ORR) was analyzed after last the dosed participant had completed 25-week evaluation. The secondary outcome measures included time to tumor progression, progression-free survival and overall survival at week 48, and safety evaluation. RESULTS: For reference and study trastuzumab products, mean Cmax of 229.02 and 210.68 µg/mL and AUC0-336 of 24298.29 and 25809.33 (µg × h/mL), respectively, were obtained. The efficacy results demonstrated that study trastuzumab and reference trastuzumab had comparable ORR (48.44% vs. 44.44%). The proportions of participants showing complete response and partial response in each arm were found to be comparable. There were 56 (68.29%) participants in the study arm and 13 (59.09%) participants in the reference arm who had at least one adverse event during the study. Immunogenicity assessment also revealed no participants with positive antibody titer in any of the study arms. CONCLUSION: The pharmacokinetics, overall response rate at 25 weeks, and safety of the biosimilar trastuzumab was comparable to the reference trastuzumab.
Subject(s)
Biosimilar Pharmaceuticals/administration & dosage , Breast Neoplasms/drug therapy , Receptor, ErbB-2/genetics , Trastuzumab/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Biosimilar Pharmaceuticals/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/classification , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , India/epidemiology , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Remission Induction , Trastuzumab/adverse effectsABSTRACT
India is getting to be known as a hot destination for executing clinical trials. It is witnessing the frenzied entry of pharma sponsor companies and contract research organizations and the movement of Indian non-healthcare groups into clinical research. In this mad melee, what are the determinants of success? How real is the promise of clinical research in India and what will make or break a new entrant in this business? This article attempts to describe these challenges and focuses on the resilient success criteria that the contract clinical research industry in India has tested every newcomer against.
