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Authors: Parag Goyal, Jyoti Iyer, Laxmi Adhikary, Bhavesh Vats, Pradeep Kabadi, Harish Pai, Daniel Ranayhossaini, Shankara Gouda, Malini Subbarao, Gaurav Mehta, Arindam Saha, Arnab Bera, Abhilashi Sahu, Maninder Kaur, Ankita Singh, Ashwani Marwah, Praveen Kumar Reddy Moole, Jeffrey Smith, Ramakrishnan Melarkode & Rajesh Ullanat.

Date: July 22nd, 2021



Aims: Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin® biosimilar, are reported

Materials & methods: Primary sequence and higher order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys.

Results: Primary structures were identical; secondary and tertiary structures were highly similar. Non-significant differences were observed for charge heterogeneity. Twelve of 13 glycan species were highly similar, with slightly higher total mannose levels in trastuzumab-dkst. FcγR and FcRn binding activity was highly similar. Each drug equally inhibited HER2+ cell proliferation, demonstrating equivalent relative potency in mediating HER2+ cell cytolysis by antibody-dependent cellular cytotoxicity. Pharmacokinetic and toxicological profiles in cynomolgus monkeys were similar.

Conclusions: Trastuzumab-dkst, US-licensed trastuzumab and EU-approved trastuzumab demonstrate high structural and functional similarity.

Financial & competing interests disclosure: This work was supported by Viatris Inc, Canonsburg, PA and Biocon Ltd, Bangalore, India. P Goyal, B Vats, D Ranayhossaini, S Gouda, G Mehta, J Smith and R Ullanat are or were paid employees of Viatris, Inc. at the time of the study and may hold stock with the company. J Iyer, L Adhikary, P Kabadi, H Pai, M Subbarao, A Saha, A Bera, A Sahu, M Kaur, A Singh, A Marwah, PK Reddy and R Melarkode are or were paid employees of Biocon Biologics Ltd at the time of the study and may hold stock with the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Editorial assistance was provided under the direction of the authors by MedThink SciCom, with support from Viatris, Inc.

Authors: Hope S. Rugo, Eduardo J. Pennella, Unmesh Gopalakrishnan, Miguel Hernandez-Bronchud, Jay Herson, Hans Friedrich Koch, Subramanian Loganathan, Sarika Deodhar, Ashwani Marwah, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D. Parra, Maria Luisa T. Abesamis-Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Mamillapalli, Sirshendu Roy, Eduardo Patricio Yanez Ruiz, Abhijit Barve, Adolfo Fuentes-Alburo & Cornelius F. Waller

Date: June 14th, 2021


Abstract –

Purpose: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE.

Methods: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient.

Results: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan–Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up.

Conclusions: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC.

Funding: This study was funded by Viatris Inc, Canonsburg, PA, and Biocon Limited, Bangalore, India.

Authors: Anjana Joel, Josh Thomas Georgy, Divya Bala Thumaty, Ajoy Oommen John, Raju Titus Chacko, Grace Rebekah, Elanthenral Sigamani, Jagan Chandramohan, Marie Therese Manipadam, Anish Jacob Cherian, Deepak Thomas Abraham, Paul Mazhuvanchary Jacob, Patricia Sebastian, Selvamani Backianathan and Ashish Singh

Date: Mar 22nd, 2021


Abstract –

Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator.

Methods:We conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator (n = 34 (33%)) and biosimilar (n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records.

Results: A total of 135 patients were analysed with a median age of 51 years (range: 23–82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3–114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients.

Conclusions: Access to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.

Authors: Cornelius F. Waller, Apinya Vutikullird, Tracey E. Lawrence, Andrew Shaw, Mark Shiyao Liu, Mark Baczkowski, Rajiv Sharma, Abhijit Barve, Parag Goyal, Charles Donnelly, Nilanjan Sengupta, and Eduardo J. Pennella

Date: July 31st, 2018


Abstract –

Aims: Trastuzumab is a humanized monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2) oncoprotein and is an effective therapy for HER2‐overexpressing breast cancer. MYL‐1401O is a trastuzumab biosimilar. Here, we report results from a phase 1 study that investigated bioequivalence among MYL‐1401O, reference EU‐trastuzumab and US‐trastuzumab.

Methods: This single‐centre, randomized, double‐blind, three‐arm, parallel‐group, phase 1 study was conducted in healthy adult male volunteers. Subjects were randomized 1:1:1 to receive a single 8 mg kg−1 dose of MYL‐1401O, EU‐trastuzumab or US‐trastuzumab as a 90‐min intravenous infusion. The primary objective was to assess PK similarity among all three products. Primary endpoints assessed were peak serum concentration (Cmax), area under the serum concentration–time curve from time of dosing to time of last quantifiable concentration and from time of dosing to infinity. Secondary endpoints included time of Cmax, elimination rate constant, half‐life, safety and immunogenicity.

Results: Of 132 subjects enrolled (44/treatment), 120 (MYL‐1401O, n = 42; EU‐trastuzumab, n = 41; US‐trastuzumab, n = 37) were included in the PK analysis. The 90% confidence intervals of the ratios of geometric means for the primary endpoints were bounded within the predefined bioequivalence criterion of 80–125%. Secondary endpoints time of Cmax, elimination rate constant and half‐life were similar among groups. All treatment‐emergent adverse events were mild or moderate, similar across groups and no serious adverse events were reported. No treatment‐related antidrug antibodies were detected.

Conclusions: MYL‐1401O was well tolerated and demonstrated PK and safety profiles similar to EU‐trastuzumab and US‐trastuzumab in healthy volunteers.

Competing Interests: C.F.W. is a consultant/advisory board member for Mylan Inc. A.V. has nothing to disclose. T.E.L., A.S., M.S.L., A.B., P.G., C.D. and E.J.P. are paid employees of Mylan Inc and may hold stock with the company. N.S. is a paid employee of Biocon Research Ltd and may hold stock with the company. M.B and R.S. were employees of Mylan Inc at the time of analysis and may hold stock with the company.

This study was supported by Mylan Inc, Canonsburg, PA, USA, and Biocon Ltd, Bangalore, India. Editorial assistance was provided under the direction of the authors by Ali Rosenberg, PhD, William Turner, PhD, and Jennifer Rossi, MA, ELS, MedThink SciCom, with support from Mylan Inc.

Authors: Hope S. Rugo, MD; Abhijit Barve, MD, PhD, MBA; Cornelius F. Waller, MD; Miguel Hernandez-Bronchud, MD, PhD; Jay Herson, PhD; Jinyu Yuan, PhD; Rajiv Sharma, MBBS, MS; Mark Baczkowski, MS, RPh; Mudgal Kothekar, MD; Subramanian Loganathan, MD; Alexey Manikhas, MD; Igor Bondarenko, MD; Guzel Mukhametshina, MD; Gia Nemsadze, MD, PhD; Joseph D. Parra, MD; Maria Luisa T. Abesamis-Tiambeng, MD; Kakhaber Baramidze, MD, PhD; Charuwan Akewanlop, MD; Ihor Vynnychenko, MD; Virote Sriuranpong, MD; Gopichand Mamillapalli, MS, MCh; Sirshendu Ray, MS; Eduardo P. Yanez Ruiz, MD; Eduardo Pennella, MD, MBA

Date: Jan 3rd, 2017


Abstract –

Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)–positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy.

Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer.

Design, Setting, and Participants: Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred.

Interventions : Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane.

Main Outcomes and Measures: The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and −15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events.

Results: Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, −3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; −1.7%; 95% CI, −11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; −0.4%; 95% CI, −9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, −2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%).

Conclusions and Relevance: Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome.

Funding/Support: The Heritage Study was funded and sponsored by Mylan Inc and Biocon Research Limited.


Authors: Joel Owen, Russell Rackley, Mark Liu, Adolfo Fuentes-Alburo, Tazeen Idris, Subramanian Loganathan, Abhijit Barve, Cornelius F. Waller, Hope S. Rugo

Date: Feb 15th, 2021


Abstract –

Background: Mylan trastuzumab (MYL-1401O) is a biosimilar to trastuzumab (Herceptin®). A multicenter, double blind, randomized, phase III study (HERITAGE) compared the efficacy, safety, Pop PK and immunogenicity of MYL-1401O and trastuzumab in patients with HER2-positive mBC. Patients were randomized 1:1 to receive either MYL-1401O or Herceptin®, in combination with taxane Q3W for 24 weeks followed by monotherapy until unacceptable toxicity, disease progression or early discontinuation.

Objectives: The objectives of the Pop PK analysis were to compare the Pop PK derived AUC, Cmax, clearance, Vd, and T1/2 profiles of MYL1401O and Herceptin® and to perform an exploratory assessment of the impact of shed extracellular domain (ECD) fragments of the HER2 receptor (HER2/ ECD) on PK parameters.

Methods: One end of infusion PK sample was collected at Cycle 1 and Cycle 6, and 1 trough sample per cycle from all patients; additional samples were taken in a Pop PK subset (MYL-1401O: 45; Herceptin®: 37) in the first dosing interval and at subsequent times. Pop PK modeling was performed using NONMEM. Individual patient empiric Bayesian parameter estimates were used to estimate PK measures. The impact of HER2/ECD presence on PK levels was evaluated in the primary covariate analysis.

Results: Two hundred forty-five (245) patients in the PK population received MYL-1401O, while 240 received Herceptin® of which 482 were included in the base model Pop PK analysis. 3170 concentration records with sufficient information were included in the Pop PK analysis. There were no notable demographic differences between the treatment groups. Bayesian parameter based exposure estimates at or near steady-state dosing were comparable between treatments, confirming similar PK (Table 1). Treatment was not a significant covariate of clearance (p=0.177) or volume of the central compartment (p=0.584) using the likelihood ratio Chi-square test.The test-to reference mean ratios of Cmin for Cycle 1 and Cycle 6 (end of cycle) were 103.11(90% CI = 90.61, 117.33) and 104.16 (90% CI = 94.00, 115.42), respectively.The HER2/ECD concentrations were a significant covariate of trastuzumab clearance.

Conclusions: Pop PK profiles of MYL-1401O vs. Herceptin® were similar in patients with HER2positive mBC. Model-based exposure measures were similar between treatments. HER2/ECD concentrations were a strong determinant of trastuzumab clearance, and clearance was similar between treatments. The observed trough concentrations were similar between treatments at the end of Cycle 1 and at Cycle 6.

Authors: Hassan Errihani, Narjiss Berrada, Mouna Khouchani, Abdelkader Acharki, Kamal Lahbabi, Hassan Jouhadi, Meryem Glaoui

Date: May 25th, 2020


Abstract –

Background: Hertraz, the first trastuzumab biosimilar was approved in Morocco in 2017. Real world data on trastuzumab biosimilars are very limited or not available. HERLife is a prospective, non-interventional phase IV study program that investigated the experience of using Hertraz, a biosimilar for trastuzumab (Herceptin), under routine clinical practice conditions in Morocco. The primary aim of this study was to confirm the acceptable safety and tolerability of Hertraz.

Methods: Ninety-nine patients with HER2-positive breast cancer treated with Hertraz were enrolled from 8 public and private sector hospitals and followed up for 12 months as part of this non-interventional study. Cardiac events (LVEF) and other unexpected or serious adverse events were monitored. The study arms consisted of patients with early breast cancer (Arm 1, n=70) and metastatic breast cancer (Arm 2, n=29) whose median age was 53 years in both groups.

Results: Switching from Herceptin to Hertraz was observed in 45% of 29 MBC patients and 27% of 70 EBC patients. Switching was done at a median of 4th cycle. Pertuzumab was used in combination with Hertraz in 69% and 19% of patients in the metastatic and neoadjuvant settings, respectively. Two patients had a decline in LVEF. One patient treated with Hertraz alone and one patient treated with Hertraz and pertuzumab developed a decrease in LVEF requiring a three-week treatment discontinuation of Hertraz. Treatment of Hertraz was continued after 1 skipped cycle without occurrence of new side effects. No other trastuzumab related adverse events was observed. Four patients in the metastatic group and 2 patients in the early breast cancer arm had a relapse in the 12 months of clinical follow-up.

Conclusions: The management of HER2+ breast cancer in Morocco follows the international recommendations. This is the first real world safety data of Hertraz from Morocco. The 12-month follow-up treatment with Hertraz showed an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Hertraz or Hertraz combined with pertuzumab, the safety profile was similar to that previously reported in other studies.

Authors: Heloisa Magda Resende, Paola Cardoso, Pedro Marassi, Maristela Seoanes Precivale, Alexandre Alcantara, Ana Carolina Cardoso, Lara Lopes Facó, Leandro Ladislau Alves, Vivienne Carduz Castilho

Date: May 25th, 2020



Background: Brazil has a complex health-care system which comprises 76% of population in the public unified health system (SUS) and only 24% in private system. Even with most of the population in the public system low resources has been allocated SUS by the government compared with that in private system. Breast cancer (BC) is the more frequent malignant neoplasm in Brazilian women, including HER2 overexpression, and the most are treated in SUS. Although, the HER2 blockage benefits in overall survival have been demonstrated since 2005, the adjuvant and neoadjuvant HER2 blockage was included in SUS protocols only 2013 while the metastatic only 2018. Brazil and development countries have limited accesses to biological drugs and target therapies due to the high cost. The biosimilar technology would improve the patient access to these drugs, health-care savings with efficacy and safety. In 2017, Brazil has approved the first biosimilar in oncology, the anti-HER2 monoclonal antibody trastuzumab-dkst. Our aim is understanding the reasons that hampered the Brazilian oncologists changing practice about biosimilars.

Methods: We submitted an on-line survey with 12 questions to 144 Brazilian oncologists which are registered in Brazilian Clinical Oncology Society from North, Northeast, Center east, Center west and Southeast regions in Brazil. The questions were about the anti-HER2 biosimilars knowledge, the manufacturing process, the costs, the biosimilars-based clinical trial, the drug efficacy and safety.

Results: We observed that all responders have 9 years experienced oncologist with mean of care 15 patient with HER2 BC per month. In total, 95% of oncologist knows biosimilar definition and 96% assume prescribe biosimilars without doubts. However, 81% oncologists would prescribe biosimilars to all patients, 82% would interchanges and 63% would extrapolate the indication.

Conclusions: This survey was conducted to understand the Brazilian oncologist knowledge about biosimilar. We demonstrated a high knowledge of biosimilar definition, however with high percentage indicated adherence barriers. The pharmacovigilance, clinical trials that support biosimilar approval and extrapolation concepts are the main aspects to be addressed. The opportunity of patient access with biosimilars is real and it is the oncologist’s duty to engage in medical education programs. This study could highlight a crucial need for greater strategies to educate physicians, to disseminate biosimilars and provide more informed decision making.

Authors: Cornelius F. Waller, Aleksei Manikhas, Eduardo J. Pennella, Igor Bondarenko, Guzel Mukhametshina, Maria Luisa Abesanis Tiambeng, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Sirshendu Ray, Miguel Hernandez-Bronchud, Jay Herson, Joseph D. Parra, Joseph D. Parra, Gia Nemsadze, Unmesh Gopalakrishnan, Subramanian Loganathan, Rafael Muniz, Abhijit Barve, Hope S. Rugo

Date: May 26th, 2019


Abstract –

Background: The multicenter, double-blind, randomized, parallel-group, phase 3 Heritage trial (NCT02472964) evaluated efficacy and safety of trastuzumab-dkst (Ogivri), a trastuzumab biosimilar, vs trastuzumab, plus taxane as first-line therapy for patients with HER2+ metastatic breast cancer. Overall response at week (wk) 24 and progression-free survival (PFS) at wk 48 have been reported (Rugo et al, JAMA 2017; ASCO 2018).

Methods: Eligible patients were randomized 1:1 to trastuzumab-dkst or trastuzumab, plus taxane. After 24 wks, patients with responding/stable disease continued monotherapy per randomization. Safety and OS during maintenance, cumulative through 36 months of follow-up from last patient on study, are described.

Results: 500 patients were randomized; 343 received monotherapy after 24 wks (trastuzumab-dkst, n = 179; trastuzumab, n = 164). 128 patients discontinued monotherapy (trastuzumab-dkst, n = 63; trastuzumab, n = 65); mean time to discontinuation was 19 months in both groups. Treatment-emergent adverse events (TEAEs) during monotherapy were similar for trastuzumab-dkst (69%) and trastuzumab (73%); most were low grade and serious TEAE rates were 6% in both groups. Cumulative rates of TEAEs of special interest were similar for hypersensitivity, pulmonary, and cardiac events (trastuzumab-dkst, 23%, 16%, and 5%; trastuzumab, 24%, 13%, and 5%). Incidences of left ventricular ejection fraction (LVEF) < 50% ≥1 time postbaseline (trastuzumab-dkst, 5%; trastuzumab, 3%) and LVEF < 50% postbaseline and ≥10% reduction (trastuzumab-dkst, 4%; trastuzumab, 3%) were low. At 36 months, 169 patients had received further lines of therapy, with similar distribution of HER2 treatments, endocrine therapies, and chemotherapies. Final median PFS was 11.1 months in both groups. Median duration of response was 9.9 and 9.8 months and median OS was 35.0 and 30.2 months for trastuzumab-dkst and trastuzumab, respectively: unstratified hazard ratio, 0.9 (95% CI, 0.70-1.17).

Conclusions: Long-term safety data with similar median OS compared with originator trastuzumab further support the safety and efficacy profile of trastuzumab-dkst.

Authors: Aleksei Manikhas, Eduardo J. Pennella, Igor Bondarenko, Guzel Mukhametshina, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Sirshendu Ray, Cornelius F. Waller, Miguel Hernandez Bronchud, Jay Herson, Subramanian Loganathan, Abhijit Barve, Hope S. Rugo

Date: June 1st, 2018


Abstract –

Background: The Heritage trial is a multicenter, double-blind, randomized, parallel-group, phase 3 study (NCT02472964) evaluating efficacy and safety of trastuzumab-dkst (Ogivri), a trastuzumab biosimilar, vs trastuzumab, in combination with taxane as first-line therapy for patients with HER2+ metastatic breast cancer. The primary endpoint, overall response rate on combination therapy at week 24, was previously reported (Rugo et al, JAMA 2017).

Methods: Eligible patients were randomized 1:1 to trastuzumab-dkst or trastuzumab, combined with taxane. After 24 weeks, patients with responding or stable disease received monotherapy as per randomization. Here, we describe secondary endpoints of safety and immunogenicity during monotherapy and cumulative through 48 weeks; progression-free survival (PFS) and event-based overall survival (OS) will be presented in the future.

Results: 500 patients were randomized, 342 continued treatment after 24 weeks, and 214 continued through 48 weeks. Treatment-emergent adverse event (TEAE) rates during monotherapy were similar (trastuzumab-dkst, 54.7%; trastuzumab, 60.1%); most were low grade. Grade ≥3 TEAEs were more frequent with trastuzumab (11.7%) vs trastuzumab-dkst (6.7%); serious TEAE rates were similar (trastuzumab-dkst, 2.8%; trastuzumab, 2.5%). When assessed over 48 weeks of combination and monotherapy, cumulative rates of TEAEs of special interest were similar for pulmonary events, significant cardiac disorders, and infusion-related events (trastuzumab-dkst, 13.0%, 4.9%, and 9.3%; trastuzumab, 12.2%, 4.1%, and 8.1%, respectively). Immunogenicity and incidence of left ventricular ejection fraction < 50% ≥1 time postbaseline and ≥10% reduction at week 48 were similar between groups (trastuzumab-dkst, 3.9% and 3.6%; trastuzumab, 4.4% and 2.8%, respectively). No new safety signals were detected. At week 48, median PFS was 11.1 months in both groups and OS curves were similar.

Conclusions: Maintenance monotherapy with FDA-approved trastuzumab-dkst after combination with taxane was well tolerated, with safety and efficacy profiles similar to originator trastuzumab.

Authors: Ashish Bajaj, Ramez Ahmed and Dilip Pawar

Date: Nov 28th, 2017



Aim: A survey was conducted to understand clinical practices in the management of breast cancer in Indian patients.

Materials & Methods: A questionnaire was developed to undertake a survey among oncologists across India in 2016. Response from 17 doctors were recorded and analyzed.

Results: Around 35.41% newly diagnosed cases, 37.53% follow-up patients and 24.12% relapsed breast cancer patients are treated by these doctors. Around 52.9% patients were of early breast cancer (EBC) and 47.1% were metastatic breast cancer (MBC). For first line therapy for HER2 positive EBC, 35.3% prefer targeted therapy, 17.6% use Trastuzumab as choice of targeted therapy and for HER2 positive MBC, 11.8% prefer targeted therapy with hormonal therapy, 11.8% use only targeted therapy and 11.8% use trastuzumab as choice of targeted therapy. For second line therapy for HER2 positive EBC, 11.8% use targeted therapy, 11.8% use targeted therapy with hormonal therapy, 11.8% use lapatinib and for HER2 positive MBC, 29.4% use Trastuzumab Emtansine (TDM1), 11.8% use targeted therapy, 11.8% use trastuzumab as choice of targeted therapy. Trastuzumab as choice of anti-HER2 agent was used in 94.1% doctors, 88.2% use lapatinib, 64.7% use Pertuzumab and 58.8% use TDM1.

Conclusions: Trastuzumab stands out as choice of targeted therapy as an anti-HER2 agent for early and metastatic breast cancer in clinical practice as reiterated in this survey with Indian oncologists.

Authors: Dilip Pawar, Ashish Bajaj and Sameer Guliani

Date: Nov 28th, 2017



Purpose: Biosimilars are available for trastuzumab globally including India. This survey was conducted across India to understand oncology practices for the use of trastuzumab innovator and biosimilars in treatment of early breast cancer (EBC) and metastatic breast cancer (MBC).

Methodology: These 20 items self-administered questionnaire was completed by 78 oncologists across India. It included the prescription trends for trastuzumab innovator and biosimilars in treatment of EBC and MBC.

Results: The oncologists reported that amongst all breast cancer patients, HER2+ cases comprised about 29.09% for EBC and 39.69% for MBC in their practice. In HER2+ cases, 58.94% patients of EBC and 52.90% of MBC are prescribed trastuzumab. Of all trastuzumab prescriptions, 32.49% of EBC and 31.34% of MBC cases are prescribed innovator brand, whereas 64.69% of EBC and 65.87% cases of MBC are prescribed biosimilar. In EBC 97.1% patients on trastuzumab completed 11-20 cycles as compared to only 40.7% MBC cases. Of all patients prescribed trastuzumab 68.3% patients completed 1-year treatment period and only 31.7% patients did not. Switchover to a biosimilar from innovator brand is 29.5% for EBC and 38.3% for MBC. The switchover from one biosimilar to other biosimilar was 19.0% in EBC and 16.4% in MBC. Cost of therapy was reported by many oncologists (64.0%) as the major reason for switchover to biosimilar. There were no differences observed in efficacy and adverse effects when switchover was done to biosimilars.

Conclusions: Biosimilars for trastuzumab can be useful cost-effective substitutes for innovator brands for treatment of HER2+ breast cancer.

Authors: Hope S. Rugo, Abhijit Barve, Cornelius F. Waller, Miguel Hernandez-Bronchud, Jay Herson, Jinyu Yuan, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D. Parra, Maria Luisa T. Abesamis Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Manillapalli, Sirshendu Ray, Eduardo Patricio Yanez Ruiz, Eduardo J. Pennella

Date: June 20th, 2016



Background: Trastuzumab has revolutionized treatment of HER2+ breast cancer. Globally accessible alternatives are a critical need. We evaluated Myl-1401O, a proposed trastuzumab biosimilar, as treatment for HER2+ metastatic breast cancer (MBC), based on physicochemical analyses, nonclinical, pharmacokinetic and pharmacodynamic studies*

Methods: Heritage is a double-blind, randomized clinical trial designed to evaluate comparative efficacy and safety of Myl-1401O vs Herceptin. Eligible patients (pts) had centrally confirmed, measurable HER2+ MBC without prior chemotherapy or trastuzumab for metastatic disease. Pts were randomized to receive either Myl-1401O or Herceptin with docetaxel or paclitaxel for a minimum of 8 cycles. Trastuzumab was continued until progression. The primary endpoint was overall response (ORR) at Week 24 by blinded central evaluation using RECIST 1.1. Secondary endpoints include progression free survival (PFS), overall survival, and safety. A sample size of 456 pts was calculated to demonstrate equivalence in ORR at Week 24 for MYL-1401O vs Herceptin, defined as a 90% confidence interval (CI) for the ratio of best ORR within the equivalence margin (0.81, 1.24).

Results: 500 pts were randomized, 458 were evaluable for efficacy. 44% had hormone receptor positive MBC, 84% received docetaxel. Week 24 ORR was 69.6% for Myl-14010 compared to 64% for Herceptin. The ratio of ORR was 1.09; both 90% CI (0.974-1.211) and 95% CI (0.954-1.237) were within the pre-defined equivalence margin. Median PFS is not yet reached (41 events for MYL-1401O vs 48 events for Herceptin). Safety was comparable; serious adverse events (primarily neutropenia related) occurred in 38% (MYL-1401O) vs 36% (Herceptin), with 4 fatal events in each arm. There was no significant change in cardiac function from baseline to Week 24 in either arm.

Conclusions: MYL-1401O was equivalent to Herceptin, given in combination with a taxane as first-line therapy for MBC, as measured by 24 week ORR. Safety was comparable. The proposed trastuzumab biosimilar MYL-1401O could be a new treatment option for HER2+ MBC.

* Presented at: British Pharmacological Society, Pharmacology Meeting;