Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial

Minckwitz, Gϋnter von; Colleoni, Marco; Kolberg, Hans‐Christian; Morales, Serafín; Santi, Patrícia Xavier; Tomašević, Zorica; Zhang, Nan; Hanes, Vladimir

doi:10.1016/s1470-2045(18)30241-9

Cited by 85 publications

(153 citation statements)

References 16 publications

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“…CT-P6 (Herzuma®, Celltrion Healthcare, Incheon, ROK/Teva Pharmaceuticals, Petach Tikwa, Israel) and PF-05280014 (Trazimera®, Pfizer, New York, NY, USA/Hospira, Lake Forest, IL, USA) were evaluated in both mBC and eBC [14,15,16,17], ABP 980 (Kanjinti®, Amgen, Thousand Oaks, CA, USA) [18] and SB3 (Ontruzant®, Samsung Bioepis, Incheon, ROK/Daewoong Pharmaceuticals, Seoul, ROK/Merck (MSD), Kenilworth, NJ, USA) [19,20] only in eBC, and MYL-1410 (Ogivri®, Biocon, Bangalore, India/ Mylan, Canonsburg, PA, USA) [21] and BCD-022 (HERtiCAD®, Biocad, Saint Petersburg, Russia) only in mBC (NCT01764022). All biosimilars were evaluated with the recommended equivalence trial design, except for BCD-022 which was evaluated in a non-inferiority trial.…”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

“…In the Lilac trial (ABP 980 vs. trastuzumab RP) which enrolled 827 patients [18], 725 patients were randomized to receive ABP 980 or the trastuzumab RP. The primary endpoint was pCR which was achieved in 172 patients.…”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

“…In the local analysis, the lower margin of the 90% CIs for risk ratio and risk difference showed non-inferiority, but the upper margin exceeded the predefined equivalence margins, meaning that non-superiority was inconclusive. In the central laboratory evaluation of tumor samples, ABP 980 and the trastuzumab RP were within the predefined equivalence margins, indicating similar efficacy (table 2) [18]. …”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

“…MYL-1410 and CT-P6 were evaluated with equivalence margins of ±15% [15,21], whereas ABP-980 and SB3 were tested with margins of ±13% [18,20]. Referring to the work of Jackisch et al [13], it is theoretically possible, albeit remaining unclear, that a 2% difference in prespecification of the equivalence margins will lead to a potential loss of long-term efficacy in terms of EFS or PFS.…”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

“…In the LILAC trial [18], 15% (n = 54) in the Kanjinti (ABP 980) group and 14% (n = 51) in the trastuzumab RP group demonstrated adverse events (AE) ≥ grade 3 during the neoadjuvant phase. Of the ≥ grade 3 AE, neutropenia was most frequently observed at 6% (n = 21) in both groups.…”

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

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Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Thill

2019

Breast Care

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In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the ‘gold standard' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.

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Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

Section: Clinical Trials For Biosimilar Trastuzumabmentioning

confidence: 99%

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Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Thill

2019

Breast Care

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Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China

Luo,

Du,

et al. 2023

JAMA Netw Open

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ImportanceThe high cost of biologics used to treat cancer has been an increasing burden in the world. In China, the recent approval of cancer biosimilar drugs to resolve this problem is promising, but evidence of clinical benefits, price, and uptake for these drugs is still lacking.ObjectivesTo compare characteristics of pivotal clinical trials in China and other countries for biosimilars of bevacizumab, rituximab, and trastuzumab and investigate the efficacy or effectiveness, safety, and immunogenicity outcomes of cancer biosimilars compared with reference drugs by meta-analysis.Data SourcesFor this systematic review and meta-analysis, PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for published studies from database inception to February 1, 2023, using the search topics (cancers) AND (biosimilars).Study SelectionRandomized clinical trials and cohort studies that included patients with cancer were included.Data Extraction and SynthesisTwo authors independently extracted the outcome estimates and characteristics for each study. A random-effects meta-analysis was performed to summarize the relative estimates with 95% CIs. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline.Main Outcomes and MeasuresClinical trial characteristics were collected for biosimilars of bevacizumab, rituximab, and trastuzumab. The relative estimates of efficacy or effectiveness (objective response rate, progression-free survival, and overall survival), safety, and immunogenicity outcomes were analyzed for biosimilars vs reference drugs. The weighted average price and uptake rate were evaluated for biosimilars relative to their reference drugs between 2015 and 2022.ResultsA total of 39 RCTs (involving 18 791 patients) and 10 cohort studies (involving 1998 patients) were included. The biosimilars of bevacizumab (16 RCTs; risk ratio [RR], 0.97; 95% CI, 0.93-1.01; P = .17), rituximab (12 RCTs; RR, 1.03; 95% CI, 0.98-1.08; P = .70), and trastuzumab (9 RCTs: RR, 1.04; 95% CI, 0.97-1.12; P = .29) met equivalence with reference biologics in regard to the objective response rate. The results summarized from cohort studies were consistent with those from RCTs. In 2022, cancer biosimilars were priced at 69% to 90% of the costs for the reference drugs, and their uptake reached 54% to 83% in China.Conclusions and RelevanceThis systematic review and meta-analysis indicated that cancer biosimilars provided comparable clinical benefits at lower prices compared with reference drugs. These findings suggest the potential feasibility of expediting the transition from reference drugs to biosimilars to benefit more patients with cancer.

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Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer

et al. 2022

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IMPORTANCE Biologics account for almost half of US drug spending but may be subject to competitive pricing pressures by US Food and Drug Administration-approved biosimilars. The extent of the preapproval clinical testing that is needed and how these biosimilars compare with the originator biologic products remain critical issues in establishing a vibrant biosimilar market.OBJECTIVES To analyze the design of cancer biosimilar efficacy studies compared with the reference drug pivotal trials and provide summary risk ratio estimates for each cancer type drug subgroup.DATA SOURCES A systematic search was performed of articles and abstracts published using Embase, PubMed/MEDLINE, and ClinicalTrials.gov, last updated April 18, 2021.STUDY SELECTION All studies or abstracts in English comparing a disease-modifying cancer biologic and its biosimilar and reporting efficacy or surrogate efficacy results were included.DATA EXTRACTION AND SYNTHESIS Outcome estimates and study characteristics were extracted from each study. Among biosimilar efficacy studies, random-effects meta-analyses were performed for each cancer type molecule outcome subgroup, calculating pooled relative estimates and 95% CIs. MAIN OUTCOMES AND MEASURESStudy characteristics, such as population size, blinding, and randomization, were compared between biosimilar trials and those of reference drugs. Risk ratio estimates for relative change to surrogate measures (eg, progression-free survival) were collected for biosimilars and their reference products.RESULTS A total of 31 cancer biosimilar studies of 3 reference products involving 12 310 patients were included. In all 7 subgroups, the biosimilars analyzed were indistinguishable from their reference drug on surrogate efficacy. Six reference drug trials were included, involving 1811 patients. On average, biosimilar studies involved more patients than reference drug trials (mean number of patients, 397 vs 302), were more likely to be randomized clinical trials rather than single-group or observational studies (100% [31 of 31] vs 50% [3 of 6]), and were more likely to be double blind rather than open label (84% [26 of 31] vs 17% [1 of 6]).CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis found that the biosimilars for the cancer drugs in this sample were subjected to rigorous clinical evaluations, and the results were statistically indistinguishable from those of original products across drugs, cancer types, and outcome measures.

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Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial

Cited by 85 publications

References 16 publications

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China

Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer

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