Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data
In vitro Untersuchung und retrospektive Analyse zu Trastuzumab-Biosimilar bei frühem Brustkrebs Neoadjuvante Darreichung, Vergleich zum Trastuzumab-Originator CT-P6 ist vergleichbar wirksam und sicher zum Trastuzum...
Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data
Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data
Bernat-Peguera A et al.
Breast. 2022 Apr;62:1-9
Abstract
After the expiration of trastuzumab data exclusivity, biosimilar drugs were approved by regulatory agencies; among them, CT-P6 which was approved for the treatment of HER2-positive early- and advanced-breast cancer (BC) in 2018. Yet, reference trastuzumab (RTZ) is often combined with pertuzumab in early BC (EBC) patients treated with chemotherapy as it significantly improves the pathological complete response rate. Unfortunately, scarce preclinical and clinical data exists about the combination of CT-P6, pertuzumab and chemotherapy. Therefore, our aim was to study in vitro and in a retrospective cohort of EBC patients, whether CT-P6 was equivalent to RTZ when combined with pertuzumab with or without taxanes. In BT-474 and SKBR3 HER2+ cells we found that CT-P6 alone or in combination with pertuzumab had the same negative effect on cell proliferation, colony formation and HER2 downregulation as well as downstream activation, as RTZ. Adding paclitaxel to these treatments increased their effectivity to a similar extent. In HER2 1+ neuregulin-secreting MB-MDA-175 cells, combinations of CT-P6 or RTZ with pertuzumab were also effective, and mainly dependent on HER3:HER2 heterodimerization. In a retrospective cohort of 44 EBC HER2+ patients treated with neoadjuvant RTZ or CT-P6 in combination with pertuzumab and chemotherapy, we found no differences in efficacy or in adverse events. Moreover, the costs of CT-P6-based treatments were reduced by 1474.07 €/patient. All together we provide pre-clinical and clinical evidence of the equivalence of CT-P6 in combination with pertuzumab and chemotherapy and suggest studying these combinations also in HER2 low/negative BC patients.
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Real-World Clinical Outcomes of Biosimilar Trastuzumab (CT-P6) in HER2-Positive Early-Stage and Metastatic Breast Cancer
Retrospektive Analyse zu Trastuzumab-Biosimilar bei frühem Brustkrebs Neoadjuvante Darreichung, Vergleich zum Trastuzumab-Originator Real-World-Daten deuten darauf hin, dass CT-P6 bei HER2-positiven Patientinnen mit Brustkrebs im Frühstadium oder metastasiertem Brustkrebs die gl...
Real-World Clinical Outcomes of Biosimilar Trastuzumab (CT-P6) in HER2-Positive Early-Stage and Metastatic Breast Cancer
Real-World Clinical Outcomes of Biosimilar Trastuzumab (CT-P6) in HER2-Positive Early-Stage and Metastatic Breast Cancer
Bae SJ et al.
Front Oncol. 2021 Jun 4;11:689587
Abstract
Background: The trastuzumab biosimilar CT-P6 has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). Here, we present the first real-world comparison of CT-P6 versus RTZ with dual HER2-targeted therapy for the neoadjuvant and palliative first-line treatment with HER2-positive EBC and metastatic breast cancer (MBC) patients in two tertiary hospitals in Korea.
Methods: We retrospectively investigated medical records in the Severance Breast Cancer Registry in Korea. We identified patients with HER2-positive EBC (n=254) who had received neoadjuvant chemotherapy with RTZ or CT-P6, plus pertuzumab, carboplatin and docetaxel (TCHP) and untreated stage IV MBC (n=103) who had received palliative first-line treatment with RTZ or CT-P6, plus pertuzumab and docetaxel (THP) between May 2014 and December 2019. The primary endpoints were pathologic complete response (pCR) in the EBC and progression-free survival (PFS) in the MBC cohort. Overall survival (OS), overall response rate (ORR), disease control rate (DCR), and cardiac safety were secondary endpoints.
Results: A similar percentage of EBC patients achieved a pCR with CT-P6 versus RTZ (74.4% [93/125]) vs 69.8% [90/129], p=0.411). For patients with MBC, median follow-up duration was 23.0 and 41.0 months for CT-P6 and RTZ groups, respectively; median PFS did not differ significantly between two groups (13.0 vs 18.0 months, 95% confidence intervals (CIs) 0.0-26.6 vs 11.3-24.7, p=0.976). The ORR, DCR, and cardiac safety profiles did not also show significant difference efficacy outcomes between two groups.
Conclusions: These real-world data suggest that biosimilar trastuzumab CT-P6 has similar effectiveness and cardiac safety to RTZ in HER2-positive EBC and MBC patients, when administered as part of dual HER2-targeted therapy with pertuzumab plus chemotherapy in the neoadjuvant or palliative setting.
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Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center
Beobachtungsstudie zum Switch vom Trastuzumab-Originator auf CT-P6 oder andere Biosimilars in der Therapie von HER2-positivem Brustkrebs Vergleich mit durchgehender Verabreichung des Trastuzumab-Originators Real-World-Daten zeigen, dass für zukünftige Umstellungen vom Tr...
Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center
Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center
Piezzo M et al.
Pharmaceutics. 2021 May 10;13(5):684
Abstract
Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer
Retrospektive Analyse zu CT-P6 bei HER2-positivem, fortgeschrittenen Magenkarzinom Vergleich zum Trastuzumab-Originator CT-P6 zeigte vergleichbare Ergebnisse in der Wirksamkeit und Sicherheit wie der Trastuzumab-Originator bei HER2-positiven Patienten mit ...
Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer
Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer
Park JH et al.
Am J Clin Oncol. 2022 Feb 1;45(2):61-65
Abstract
Objectives: Treatment with trastuzumab and chemotherapy significantly improves the outcome in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). CT-P6 (trastuzumab-pkrb; Herzuma) is a trastuzumab biosimilar approved for the treatment of HER2-positive gastric cancer. In this study, we aimed to compare the efficacy and safety of CT-P6 and reference trastuzumab as first-line treatment for HER2-positive AGC.
Materials and Methods: The medical records of 102 patients with HER2-positive AGC treated with first-line trastuzumab-based chemotherapy were retrospectively reviewed. These patients were treated with either reference trastuzumab (n=72) or a biosimilar (n=30). Treatment outcomes, such as objective response rate, progression-free survival (PFS), and overall survival (OS), were compared between the reference and biosimilar groups.
Results: The objective response rate of both groups (52.8% and 56.8% in the reference and biosimilar groups, respectively) were comparable (P=0.72). No statistically significant difference was observed with the reference versus biosimilar trastuzumab for PFS (median PFS, 6.9 vs. 5.4 mo; P=0.98) or OS (median OS, 12.3 mo vs. not reached; P=0.42). Safety profiles were similar between the 2 groups.
Conclusions: Biosimilar trastuzumab showed equivalent outcome to reference trastuzumab, with similar adverse events. Biosimilar trastuzumab can suitably and safely replace trastuzumab as a reference for the treatment of HER2-positive AGC.
Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer
Retrospektive Analyse zu 30-Minuten-Infusionen mit Trastuzumab in der Erhaltungstherapie von Patienten mit HER2-positivem Magenkarzinom In der Erhaltungstherapie von Patienten mit HER2-positivem Magenkarzinom wurden 30-minütige Trastuzumab-Infusionen gut vertragen, wiesen ein ...
Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer
Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer
Oh SY et al.
Cancer Chemother Pharmacol. 2019 Mar;83(3):501-508
Abstract
Purpose: To investigate the safety and efficacy of 30-min maintenance infusions of trastuzumab in advanced gastric cancer positive for human epidermal growth factor receptor 2 (HER2).
Methods: This was a retrospective study conducted across five Korean hospitals in patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with first-line, 3-weekly trastuzumab plus chemotherapy. The first dose of trastuzumab (8 mg/kg) was administered as a 90-min infusion, with all subsequent maintenance infusions (6 mg/kg) given over 30 min. The primary aim was to investigate infusion-related reactions and cardiac events with 30-min infusions of trastuzumab. Objective response rate, progression-free survival, and overall survival were secondary endpoints.
Results: The study included 128 patients (efficacy population), of whom 123 received both induction and maintenance infusions and formed the safety population. The median age was 63 years; 80% were presenting for the first time with metastatic disease, and 94% were treated with trastuzumab plus capecitabine/cisplatin. Infusion-related reactions were observed in 32 of 123 patients (26%). There were no cardiac events. The most frequent adverse events were anorexia and nausea, followed by vomiting, fatigue, mucositis, sensory neuropathy, and hand–foot syndrome. Most events were grade 1–2 and were manageable. No patient discontinued study treatment due to adverse events. The objective response rate was 63%, and included 6 complete responses.
Conclusions: Trastuzumab 30-min maintenance infusions were well tolerated with a good safety profile, and resulted in sustained efficacy in patients with HER2-positive advanced gastric cancer.
The safety and clinical effectiveness of rapid infusion with CT‐P10 in patients with non‐Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non‐interventional post‐authorization safety study in Europe
Multizentrische Studie zur Schnellinfusion mit CT-P10 bei Patienten mit chronisch lymphatischer Leukämie (CLL) und Patienten mit Non-Hodgkin-Lymphom (NHL), Zwischenanalyse nach sechs ...
The safety and clinical effectiveness of rapid infusion with CT‐P10 in patients with non‐Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non‐interventional post‐authorization safety study in Europe
The safety and clinical effectiveness of rapid infusion with CT‐P10 in patients with non‐Hodgkin's lymphoma or chronic lymphocytic leukemia: A retrospective non‐interventional post‐authorization safety study in Europe
Bishton M et al.
Hematol Oncol. (2022); 1-11
Abstract
Rapid infusion (RI) of the rituximab biosimilar CT-P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT-P10 and reference rituximab are known to be frequently administered using an RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT-P10 in patients with NHL and CLL are limited. Hence, this study collected real-world safety and effectiveness data on RI-CT-P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion-related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%-15%; n = 20/196) of patients experienced an infusion-related reaction (IRR) on day 1-2 post-index, which was not significantly different (p = 0-45) to the IRR rate for rituximab described in a previous meta-analysis (8.8%). During the observation period, 2% of patients experienced grade 3-5 IRRs and 85% (n = 166) experienced an adverse event (non-IRR). The most common reason for discontinuation of first-line CT-P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT-P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real-world study demonstrate that the safety and effectiveness profile of RI-CT-P10 is similar to RI of reference rituximaband therefore support the current use of RI-CT-P10 in patients with NHL and CLL.
Real-world use and acceptance of rituximab biosimilars in non-Hodgkin lymphoma in an oncologist network in Germany
Auswertung von Real-World-Daten aus onkologischen Praxen in Deutschland zum Einsatz von Biosimilars bei der Therapie von chronischer lymphatischer Leukämie (CLL) und Non-Hodgkin-Lymphom (NHL) mit Rituximab Vergleich zum EU-Rituximab-Originator Die Ergebnisse der Analyse von Real-World...
Real-world use and acceptance of rituximab biosimilars in non-Hodgkin lymphoma in an oncologist network in Germany
Real-world use and acceptance of rituximab biosimilars in non-Hodgkin lymphoma in an oncologist network in Germany
Otremba B et al.
Future Oncol. 2021 Jan;17(1):117
Abstract
Aim: Present real-world data for rituximab (biosimilar and reference)-containing regimens in extrapolated indications in non-Hodgkin lymphoma (NHL)/chronic lymphocytic leukemia (CLL).
Patients & methods: Data collected from office-based oncologic practices in Germany (July 2017–June 2019).
Results: Of 1741 patients, 1241 had NHL; 500 had CLL. Of 7595 therapy cycles, 28.3% used reference rituximab; 55.2% used rituximab biosimilars; 2.0% used subcutaneous rituximab; 14.5% used rituximab, not otherwise specified. Rituximab biosimilars were used across all indications; 57.3% of cycles were administered in extrapolated indications. Over 24 months, the proportion of rituximab prescriptions that were for biosimilars increased from 12.0 to 83.0%.
Conclusion: Our real-world data in NHL and CLL depicts increasing use of rituximab biosimilars across multiple treatment protocols, including extrapolated indications.
Rapid infusion with CT-P10 in patients with non-hodgkin’s lymphoma or chronic lymphotic leukemia: interim results from European non-interventional post-authorisation safety study
Multizentrische Studie zur Schnellinfusion mit CT-P10 bei Patienten mit chronisch lymphatischer Leukämie (CLL) und Patienten mit Non-Hodgkin-Lymphom (NHL), frühe Zwischenanalyse Vergleich zur Schnellinfusion mit dem EU-Rit...
Rapid infusion with CT-P10 in patients with non-hodgkin’s lymphoma or chronic lymphotic leukemia: interim results from European non-interventional post-authorisation safety study
Rapid infusion with CT-P10 in patients with non-hodgkin’s lymphoma or chronic lymphotic leukemia: interim results from European non-interventional post-authorisation safety study
Bishton M et al.
EHA Library (2019)
Abstract
Background: CT-P10 is the first biosimilar of rituximab to be approved in Europe for treatment of rheumatic diseases and specific blood cancers including non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are subtypes of NHL. To minimise the risk of infusion-related reactions (IRRs), the recommended rituximab administration protocol is a slow initial infusian rate with gradual up-titration; however, this can be time and resource intensive for patients and healthcare providers. Consequently, rapid infusion protocols are now used widely for second and subsequent infusions in patients with no serious complications from their first infusion. Rapid infusion of rituximab has been shown to be generally well-tolerated, with an IRR rate of 8.8% reported in a recent meta-analysis; however, there are limited data on the safety of rapid infusion of CT-P10.
Aims: To evaluate the safety and effectiveness of rapidly infused CT-P10 in patients with NHL or CLL in a real world clinical setting.
Methods: This non-interventional post-authorisation safety study is in progress in four European countries (United Kingdom [UK], Spain, France, Italy). The study involves the collection of data from the medical records of patients with NHL or CLL who received rapidly-infused CT-P10 during standard clinical care. The primary outcome is incidence of IRRs (an adverse event [AE] from a pre-defined list occurring on day 1 or day 2 post-index). Secondary outcomes include the overall safety profile of rapidly-infused CT-P10 in the 6 months post-index, clinical effectiveness, treatment patterns and patients' demographic and clinical characteristics.
Conclusions: This is the first multi-country study to investigate the safety and effectiveness of rapidly infused CT-P10 in a real world setting. Early results suggest that the IRR rate for rapidly infused CT-P10 is similar to rates previously reported for reference rituximab.
Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study
Multizentrische Studie zur Schnellinfusion mit CT-P10 bei Patienten mit chronisch lymphatischer Leukämie (CLL) und Patienten mit Non-Hodgkin-Lymphom (NHL), Zwischenanalyse nach sechs Monaten Vergleich zur ...
Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study
Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study
Bishton M et al.
Blood (2019) 134 (Supplement 1): 4135
Abstract
Background: In February 2017, CT-P10 became the first rituximab biosimilar to be approved in Europe for treatment of rheumatic diseases and specific blood cancers including non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). More recently, CT-P10 was approved in the US for NHL. Although the recommended rituximab administration protocol is a slow initial infusion rate with gradual up-titration, rapid infusion protocols are used widely in patients with no serious complications from their first infusion. There are limited data on the safety of rapidly infused CT-P10.
Aims: To evaluate the safety and effectiveness of rapidly infused CT-P10 in patients with NHL or CLL in a real world clinical setting over a 6 month follow up period.
Methods: This non-interventional post-authorisation safety study is in progress in the United Kingdom (UK), Spain, France and Italy. It involves collection of data from the medical records of consenting adult patients with NHL or CLL who received rapidly-infused CT-P10 (total infusion time ≤90 minutes) during routine clinical practice. The index date (day 1) is the date of the first rapid CT-P10 infusion. Safety and effectiveness data have been collected over a 6 month observation period from the index date (or to death, if sooner). Early results from this study have been previously presented and showed the index IRR rate (the primary outcome) to be 8% (Bishton, 2019). Updated interim results with full 6 month follow-up are now available for 112 patients and are reported here, based on a data cut on 19 June 2019.
Results: This interim analysis includes patients enrolled from the UK, Italy and Spain. Ninety four patients (84%) have NHL (68 [61%] diffuse large B-cell lymphoma [DLBCL], 26 [23%] follicular lymphoma [FL]) and 18 (16%) have CLL. Other patient characteristics at index date: 74 (66%) male; median age 67 years (interquartile range [IQR] 58.0-74.0); median disease duration 0.2 years (IQR 0.1-0.4); 20 (18%) patients with prior treatment recorded (n=111); Ann Arbor stage for NHL at index (n=58): I (n=7, 12%), II (n=7, 12%), III (n=8, 14%), IV (n=35, 60%) or other (n=1, 2%; recorded as '1E'); Binet stage for CLL at index (n=11): A (n=5, 45%), B (n=4, 36%) or C (n=2, 18%). Patients had between 1 and 4 CT-P10 infusions prior to the index date, with first infusions given over a median of 4 hours (IQR 3.5-4.1 hours). Median CT-P10 dose at index was 375 mg/m2 (IQR 375.0-375.0 mg/m2) and a median of 5 infusions per patient (IQR 3.8-6.0) were given over 6 months. A total of 512 CT-P10 infusions were given over the 6 month observation period across all 112 patients. Of 19 (17%) patients who experienced one or more IRRs over the observation period (including index IRRs), 9 patients had one, 5 had two and 5 had three or more IRRs. Thirty six IRRs were reported in total and are listed in Table 1 by grade. Ninety six (86%) patients experienced an adverse event (AE) and 31 (28%) experienced a serious AE (SAE) over the observation period. At 6 months post-index, 95 (85%) patients had discontinued first line CT-P10 due to planned completion of their treatment course, 7 (6%) had discontinued due to AEs, 1 (1%) due to disease progression and 5 (4%) due to other reasons (reason for discontinuation not known for 1 patient [1%]), with treatment ongoing for 3 patients (3%). Best responses to CT-P10 during the observation period (as documented by the local investigator) were complete response (n=83, 74%), partial response (n=24, 21%), stable disease (n=3, 3%) and progressive disease (n=2, 2%).
Summary/conclusions: In this multi-country study of patients treated with rapidly-infused CT-P10 in a real world setting, a high proportion of patients achieved complete or partial responses over 6 months follow-up. The results also suggest that CT-P10 is generally well-tolerated, with 36 (predominantly mild) IRRs recorded over a total of 512 infusions, and the majority of patients discontinuing CT-P10 due to planned completion of treatment.
Evaluation of the Safety and Tolerability of Rapid Infusion of Biosimilar Rituximab Truxima® — the University College London Hospitals (UCLH) Experience
Studie zur Schnellinfusion mit CT-P10 bei Patienten mit chronisch lymphatischer Leukämie (CLL) und Patienten mit Non-Hodgkin-Lymphom (NHL) Vergleich zur Schnellinfusion mit dem EU-Rituximab-Originator Real-World-Daten belegen, dass in der Erhaltun...
Evaluation of the Safety and Tolerability of Rapid Infusion of Biosimilar Rituximab Truxima® — the University College London Hospitals (UCLH) Experience
Evaluation of the Safety and Tolerability of Rapid Infusion of Biosimilar Rituximab Truxima® — the University College London Hospitals (UCLH) Experience
Shaw R et al.
Blood (2017) 130 (Supplement 1): 3387
Abstract
Rituximab is a chimeric anti-CD20 monoclonal antibody approved in the EU (MabThera®; Roche) and US (Rituxan®; Genentech) to treat non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).
In April 2017 the first biosimilar rituximab (Truxima®; NAPP) was approved in the UK for all indications of the reference biologic. Its adoption is expected to deliver a significant reduction in treatment costs.
Administration of rituximab is associated with infusion-related reactions (IRRs). The incidence of IRRs is greatest with the first infusion and decreases significantly with subsequent infusions.
To reduce the risk of IRRs, manufacturers recommend that the first dose is gradually increased every 30 minutes in 50mg/hour increments to a maximum of 400mg/hour. For subsequent infusions gradually increase every 30 minutes in 100mg/hour increments to a maximum of 400mg/hour, known as standard subsequent rate infusion. This means a typical rituximab infusion can take 4-6 hours.
If the first infusion is well-tolerated, it is now widespread practice to administer subsequent MabThera® doses as a rapid infusion over 90 minutes, whereby 20% of the dose is given over the first 30 minutes, with the remaining 80% over the following 60 minutes (Sehn et al, Blood 2007).
Reverting to slower infusion rates with the introduction of biosimilar rituximab could adversely impact daycare unit capacity, nursing resource, appointment length, and patient satisfaction.
Aim: The aim of our study was to assess the safety of rapid infusion of Truxima® by reviewing infusion related adverse events in patients 1) switching from MabThera® 2) with previous exposure to MabThera® but last dose received over 6 months ago and 3) rituximab naïve patients.
Method: In May 2017 all patients were switched from MabThera® to Truxima® at UCLH, London. Truxima® doses given between 22nd May and 26th July 2017 were identified from the electronic prescribing system (Chemocare®). Infusion-related reactions were noted from nursing infusion records and graded using Common Terminology Criteria for Adverse Events version 4.03.
Patients who had been receiving MabThera® as a rapid infusion continued at this rate with Truxima®. Those patients who had received only one prior dose of MabThera® at the standard first dose infusion rate received their first Truxima® dose as a rapid infusion.
Patients who had not received MabThera® for over 6 months or were MabThera® naïve, received their first Truxima® dose at the standard first dose infusion rate. If well-tolerated, subsequent doses were given as a rapid infusion.
All patients received premedication with paracetamol (acetaminophen) and antihistamine.
Results: Table 1 shows the patient characteristics, MabThera® and Truxima® infusion rates and infusion-related reactions.
Discussion: The results showed that rapid infusion of Truxima® was well-tolerated in all three groups of patients. Additionally, patients switching from MabThera® safely received their first Truxima® dose as a rapid infusion. One patient switching from MabThera® developed tachycardia during their first Truxima® dose at rapid infusion rate; however this patient was able to receive subsequent Truxima® doses with additional glucocorticoid pre-medication without IRRs.
Grade 2 or 3 IRRs were observed with 8 first rate infusions (12%) and 4 of the patients have received further Truxima® doses so far. These patients received their next dose at standard subsequent infusion rate with glucocorticoid pre-medication without incident, and 2 of the patients have had further doses as a rapid infusion without an IRR. Updated results will be presented at the ASH meeting 2017.
Conclusion: This study is the first reported post-marketing experience of rapid infusion of biosimilar rituximab and showed that patients can be safely switched from MabThera® to Truxima® without reverting to slower infusion rates. In addition patients who tolerated their first infusion rate of Truxima® were able to tolerate a rapid infusion rate with subsequent doses.
These findings will facilitate the introduction of Truxima® at centres prescribing rituximab without adversely impacting resource utilisation or patient experience.
The clinical outcomes of rituximab biosimilar CT-P10 (Truxima®) with CHOP as first-line treatment for patients with diffuse large B-cell lymphoma: real-world experience
Analyse von Real-World-Daten zur Wirksamkeit und Sicherheit von CT-P10 bei diffusem großzelligen B-Zell-Lymphom (DLBCL) Vergleich zum Rituximab-Originator Die Real-World-Daten belegen die Nicht-Unterlegenheit von CT-P10 im Vergleich...
The clinical outcomes of rituximab biosimilar CT-P10 (Truxima®) with CHOP as first-line treatment for patients with diffuse large B-cell lymphoma: real-world experience
The clinical outcomes of rituximab biosimilar CT-P10 (Truxima®) with CHOP as first-line treatment for patients with diffuse large B-cell lymphoma: real-world experience
Lee K et al.
Leuk Lymphoma. 2020 Jul;61(7):1575-1583
Abstract
We evaluated real-world effectiveness and safety of CT-P10 (Truxima®) compared with originator rituximab in diffuse large B-cell lymphoma (DLBCL) treatment. Before and after the introduction of CT-P10 to our institute (November 2017), 221 newly-diagnosed DLBCL patients received rituximab with standard cyclophosphamide, vincristine, doxorubicin and prednisone. Patients received originator rituximab throughout (n = 95), switched from originator rituximab to CT-P10 (n = 36), or received CT-P10 throughout (n = 90). There were no significant differences between groups in overall response rate (91.6% vs 94.4% vs 96.7%, respectively; p = 0.403) or complete response rate (84.2% vs 77.8% vs 86.7%, respectively; p = 0.467). Kaplan–Meier survival curves also showed no significant differences in progression-free survival and overall survival between groups (log-rank p = 0.794 and p = 0.955, respectively). Safety profiles were comparable between treatment groups. These data support the ability of CT-P10 to successfully replace originator rituximab in DLBCL treatment and, given the lowered financial barrier, to improve the overall prognosis for DLBCL patients.
Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-Cell lymphoma: Interim results from a European non-interventional post-authorisation safety study
Europäische Studie zur Wirksamkeit und Sicherheit von CT-P10 bei Patienten mit diffus großzelligem B-Zell-Lymphom (DLBCL), Primäranalyse Vergleich zum EU-Rituximab-Originator Erste Ergebnisse einer Analyse von Real...
Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-Cell lymphoma: Interim results from a European non-interventional post-authorisation safety study
Real-world clinical effectiveness and safety of CT-P10 in patients with diffuse large B-Cell lymphoma: Interim results from a European non-interventional post-authorisation safety study
Bishton M et al.
EHA Library (2019)
Abstract
Background: In February 2017, CT-P10 became the first biosimilar of rituximab to be approved in Europe for treatment of rheumatic diseases and specific blood cancers including non-Hodgkin's lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the commonest type of NHL, representing an estimated 40-58% of cases. To date, no studies have investigated the clinical effectiveness or safety of CT-P10 in patients with DLBCL in the real world clinical setting.
Aim: To evaluate the real world clinical effectiveness and safety of CT-P10 in patients with DLBCL in Europe.
Methods: This non-interventional post-authorisation safety study is in progress in five European countries (France, Germany, Italy, Spain and the United Kingdom [UK]). The study involves collection of data from the medical records of patients with DLBCL who were treated with CT-P10 as part of their routine clinical care. The primary objective is to describe the clinical effectiveness of CT-P10 (overall survival, progression free survival, CT-P10 responses), with secondary objectives to describe the safety profile and CT-P10 treatment pathways. Response to CT-P10 is as documented by the local investigator.
Results: The interim analysis includes 151 patients enrolled from sites in the UK and Spain, with a median (interquartile range [IQR] of 8.9 (6.1-12.6 months post-index observation at the cut-off date for interim analysis. Patients were receiving CT-P10 as a first-line (91% [n=138/151]), second-line (6% [n=9/151]) or third-line (3% [n=4/151]) DLBCL treatment.
Conclusions: Early results from this ongoing study suggest that a high proportion of patients with DLBCL treated with CT-P10 in the real world achieve complete or partial responses, similar to the response rates reported previously for reference rituximab. Continued recruitment and extended follow-up will enable more comprehensive analyses of CT-P10 effectiveness and safety.
Responses to R-CHOP chemotherapy incorporating biosimilar Rituximab (Truxima®) for the first line treatment of diffuse large B-Cell lymphoma – initial experience at university college London hospital
Analyse zur Wirksamkeit und Sicherheit von CT-P10 bei Patienten mit diffus großzelligem B-Zell-Lymphom (DLBCL) Vergleich zum EU-Rituximab-Originator Ergebnisse einer Analyse von Real-World-Daten zeigen...
Responses to R-CHOP chemotherapy incorporating biosimilar Rituximab (Truxima®) for the first line treatment of diffuse large B-Cell lymphoma – initial experience at university college London hospital
Responses to R-CHOP chemotherapy incorporating biosimilar Rituximab (Truxima®) for the first line treatment of diffuse large B-Cell lymphoma – initial experience at university college London hospital
Cheesman S et al.
EHA Library (2019)
Abstract
Background: In April 2017 the first biosimilar rituximab (Truxima®; NAPP) was approved in the UK for all indications of the reference biologic (MabThera®; Roche). The adoption of biosimilars is expected to deliver significant cost savings in the treatment of many conditions. The approval of Truxima® was based on comprehensive analytical and pre-clinical testing together with confirmatory clinical trials in advanced follicular lymphoma and rheumatoid arthritis with subsequent extrapolation to all licensed indications of MabThera®. There is an absence of clinical trial data supporting the use of biosimilar rituximab in other haematological malignancies, including diffuse large B-cell lymphoma (DLBCL) where the standard of care is R-CHOP chemo-immunotherapy. In the clinical trial leading to the approval of MabThera® for this indication the complete response rate at the end of treatment was 76% in patients who received R-CHOP compared to 62% in the group who received CHOP alone.
Aims: To assess the response to treatment for all patients treated for de novo stage II-IV DLBCL with R-CHOP chemo-immunotherapy including biosimilar rituximab (Truxima®).
Methods: All patients starting treatment with R-CHOP for de novo stage II-IV DLBCL were identified from the electronic chemotherapy prescribing system and the following data collected: baseline demographics, performance status, staging, Revised International Prognostic Index (R-IPI), brand of rituximab received, number of R-CHOP cycles received, number of rituximab doses received, CNS prophylaxis received and response to therapy as assessed by end of treatment PET scan.
Results: A total of 70 patients have completed treatment with R-CHOP chemo-immunotherapy incorporating biosimilar rituximab (Truxima®). Patients received a median of 6 cycles of CHOP (range: 1-6) and 6 doses of rituximab (range: 2-8). 58 patients completed treatment exclusively with Truxima®. 12 patients switched from MabThera® to Truxima® during their treatment after a median of 3 doses (range: 1-6). Response rates for the whole cohort of patients were as follows: Complete Response (CR): 51/70 (73%), Partial Response (PR): 11/70 (16%), Progressive Disease (PD): 6/70 (9%). Two patients died before response could be assessed. 4/70 (6%) patients switched from R-CHOP to R-GCVP chemo-immunotherapy after a median of 2 cycles (range: 1-5); all four patients achieved a CR.
A prospective observational study to assess efficacy and safety of rituximab biosimilar in Italian pemphigus patients
Analyse von Real-World-Daten zur Wirksamkeit und Sicherheit von CT-P10 bei Pemphigus vulgaris, vegetans und foliaceus Real-World-Daten von 24 Patienten deuten auf ein gutes Wirksamkeits- und Sicherheitsprofil der Behandlung von Pemphigus-Patienten mit CT-P10 hin.
A prospective observational study to assess efficacy and safety of rituximab biosimilar in Italian pemphigus patients
A prospective observational study to assess efficacy and safety of rituximab biosimilar in Italian pemphigus patients
Di Zenzo G et al.
ESDR (2019) Sep 18-21
Abstract
Pemphigus is a chronic autoimmune blistering disease affecting both the skin and mucous membranes. Rituximab, a biological drug targeting B cells, has recently proved to be effective in pemphigus treatment. As rituximab’s patent is expired, biosimilars have been increasingly used. At present, the rituximab biosimilar CT-P10 is one of the most widely used for pemphigus treatment in Italy. EMA and AIFA approval is based on studies on rheumatic and oncological patients. No data on the use of CT-P10 in pemphigus are available.
In this study we report preliminary data on pemphigus patients treated with rituximab biosimilar obtained from 4 Italian specialized dermatological hospitals. Clinical score, anti-desmoglein (Dsg) 1 and 3 levels, clinical outcome and adverse events during follow-up were assessed.
A total of 24 patients (18 pemphigus vulgaris,1 vegetans and 5 foliaceus) were enrolled. The mean age was 52.5 years (range 35-73) and the mean follow-up time was 5.3 months (range 1-12). A notable decrease in clinical score that paralleled anti-Dsg 1 and 3 titers was observed. Mean delay to achieve disease activity control was 6.8 wks (range 1-32). At 6 months after rituximab infusion only 1 of 16 patients (6%) relapsed and 12 of 16 patients (75%) obtained remission (2 partial remission on therapy, 3 partial remission off therapy, 2 complete remission on therapy and 5 complete remission off therapy). No serious adverse events or infections have been observed. Infusion related reactions led to drop out in 2 of 24 patients (8%).
Although only preliminary conclusions can be drawn, the present findings suggest that administration of rituximab biosimilar in pemphigus patients is associated with desirable outcomes in terms of efficacy and safety.
Comparison of outcomes using the rituximab originator MabThera with the biosimilar Truxima in patients with ANCA-associated vasculitis
Retrospektive Analyse von Real-World-Daten zur Wirksamkeit und Sicherheit von CT-P10 bei Vaskulitiden Vergleich mit dem EU-Rituximab-Originator Real-Word-Daten belegen die Vergleichbarkeit von CT-P10 gegenüber dem EU-Rituximab-Originator bei der Behandlung von Vasku...
Comparison of outcomes using the rituximab originator MabThera with the biosimilar Truxima in patients with ANCA-associated vasculitis
Comparison of outcomes using the rituximab originator MabThera with the biosimilar Truxima in patients with ANCA-associated vasculitis
Antonelou M et al.
Scand J Rheumatol. 2022 Mar;51(2):135-141
Abstract
Objectives: The use of rituximab (MabThera®), an anti-CD20 monoclonal antibody, is the most significant development in the management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) since the introduction of cytotoxic therapy in 1950. Truxima® is the first anti-CD20 biosimilar approved for the same indications, and has been available in the UK since 2017. Significant cost savings have been reported when switching to biosimilars, which could lead to greater patient access to such treatment. Therefore, it is important to know whether patients’ clinical and laboratory parameters respond equally well to biosimilars as to reference medicines, tested in clinical trials.
Method: We retrospectively reviewed the clinical outcomes and laboratory parameters in 257 consecutive patients treated with anti-CD20 depletion therapy using MabThera or Truxima, for induction and maintenance of remission, in two tertiary renal centres between 2010 and 2019.
Results: We demonstrated no difference between patients treated with MabThera or Truxima in rates of remission, relapse, and hospitalization with infection when used for either induction or maintenance of remission of AAV. In one hospital subgroup analysis, we showed comparable levels of hypogammaglobulinaemia, B-cell depletion, and frequency of infusion reactions, with no significant differences.
Conclusion: The efficacy and safety of the rituximab biosimilar Truxima are not inferior to the originator MabThera in patients with AAV. Truxima represents a cheaper and safe therapeutic alternative that could increase patient access to rituximab.
Rituximab biosimilar prevents poor outcomes of microscopic polyangiitis and granulomatosis with polyangiitis as effectively as Rituximab originator
Retrospektive Analyse von Real-World-Daten zur Wirksamkeit und Sicherheit von CT-P10 bei Polyangiitis und Granulomatose Vergleich mit dem EU-Rituximab-Originator Real-Word-Daten belegen die Vergleichbarkeit von CT-P10 gegenüber dem EU-Rituximab-Origina...
Rituximab biosimilar prevents poor outcomes of microscopic polyangiitis and granulomatosis with polyangiitis as effectively as Rituximab originator
Rituximab biosimilar prevents poor outcomes of microscopic polyangiitis and granulomatosis with polyangiitis as effectively as Rituximab originator
Chan Kwon H et al.
Yonsei Med J. 2020 Aug;61(8):712-719
Abstract
Material and Methods: We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®.
Real-world intensive safety monitoring of biosimilars rituximab and trastuzumab in a Portuguese oncology hospital
Retrospektive Analyse von Real-World-Daten aus einem portugiesischen Klinikum zur Sicherheit von CT-P6 und CT-P10 in der Onkologie Real-Word-Daten belegen ein vertretbares Sicherheitsprofil ohne neue Sicherheitssignale beim Einsatz von CT-P6 und CT-P10 in der Onkologie.
Real-world intensive safety monitoring of biosimilars rituximab and trastuzumab in a Portuguese oncology hospital
Real-world intensive safety monitoring of biosimilars rituximab and trastuzumab in a Portuguese oncology hospital
Mendes D et al.
J Oncol Pharm Pract. 2021 Sep;27(6) :1432-1438
Abstract
Purpose: The aim of this study was to assess the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital.
Methods: This hospital-based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima®) or trastuzumab biosimilar CT-P6 (Herzuma®) were recruited over an 11-month and a 6-month period, respectively. Clinicians identified eligible patients and used paper-based forms to report all ADRs associated with biosimilar medicines. ADR case reports were assessed for seriousness, expectedness and causality in the Pharmacovigilance Unit of Coimbra.
Results: Ninety-four patients received biosimilar medicines (rituximab, n = 35; trastuzumab, n = 59). Of those, 4 patients (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related with biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 was chest discomfort (n = 4; 19.1%), followed by odynophagia (n = 2; 9.5%). Trastuzumab CT-P6 was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n = 1; 4.8%).
Conclusion: The results of this study suggest that using biosimilar rituximab and biosimilar trastuzumab to treat cancer patients in the real-world clinical setting is associated with acceptable safety profiles. No new safety problems were identified.