A randomized, double-blind, phase III study comparing SB3 (trastuzumab biosimilar) with originator trastuzumab in patients treated by neoadjuvant therapy for HER2-positive early breast cancer.

509 Background: SB3, a proposed biosimilar to the originator trastuzumab (TRZ), demonstrated similarity to its originator in terms of biological activities and pharmacokinetic (PK) equivalence. This study compared SB3 to TRZ in terms of efficacy, safety, PK, and immunogenicity in patients treated by neoadjuvant therapy for HER2 positive early breast cancer (NCT02149524). Methods: Phase III, randomized, double blind, multicenter study compared neoadjuvant SB3 or TRZ for 8 cycles concurrently given with chemotherapy (docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide). Then patients underwent surgery followed by 10 cycles of SB3 or TRZ. The primary endpoint was breast pathologic complete response (bpCR) rate. Equivalence was declared if the 90% confidence interval (CI) of the ratio or the 95% CI of the difference of the bpCR rates in the per-protocol set (PPS) were contained within the pre-defined equivalence margins (0.785, 1.546) and (-13%, 13%), respectively. Secondary endpoints were total pathologic complete response (tpCR), overall response rate (ORR), event-free survival, PK, immunogenicity, and safety. Results: 800 patients were included in PPS. The bpCR rates were 51.7% for SB3 and 42.0% for TRZ. The ratio of bpCR rate was 1.259 and its 90% CI was 1.112-1.426, within the pre-defined equivalence margin. The difference of bpCR rate was 10.70% and its 95% CI was 4.13-17.26; the lower margin was contained within, the upper margin was outside the pre-defined equivalence margin. Secondary endpoints were comparable between SB3 vs TRZ: tpCR rate (45.8% vs 35.8%); ORR (96.3% vs 91.2%). Safety was comparable between SB3 vs TRZ during neoadjuvant period: incidence of treatment-emergent adverse events (96.6% vs 95.2%), most commonly neutropenia, alopecia, and nausea; incidence of serious adverse events (10.5% vs 10.7%). PK equivalence was demonstrated and immunogenicity between SB3 vs TRZ was comparable (0.7% vs 0.0%). Conclusions: Equivalence was demonstrated between SB3 and TRZ based on the ratio of bpCR rates. Safety, PK, and immunogenicity were similar. Complete safety and survival data will follow. Clinical trial information: NCT02149524.

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Survival outcomes of the NeoALTTO study: Updated results of a randomized multicenter phase III neoadjuvant trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.512 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 512-512 ◽

Cited By ~ 4

Author(s):

Jens Bodo Huober ◽

Eileen McCormick Holmes ◽

Jose Baselga ◽

Evandro De Azambuja ◽

Michael Untch ◽

...

Keyword(s):

Hormone Receptor ◽

Pathologic Complete Response ◽

Complete Response ◽

Phase Iii ◽

Negative Group ◽

Her2 Positive ◽

Secondary Endpoints ◽

Landmark Analyses ◽

Pathologic Complete Response Rate

512 Background: In the neoadjuvant NeoALTTO trial dual HER2 blockade with lapatinib (L) plus trastuzumab (T) combined with weekly paclitaxel significantly increased the pathologic complete response rate (pCR) compared with either anti-HER2 agent alone plus paclitaxel. At first analysis pts with pCR had a better event free survival (EFS) and overall survival (OS) after median follow-up of 3.84 yrs. Methods: 455 pts with operable HER2-positive breast cancer were randomized to receive either L (n=154) 1500mg/day, T 4mg/kg loading dose followed by 2mg/kg/wk (n=149) or L 1000mg/day plus T (n=152) for 6 weeks followed by the assigned anti-HER2 treatment combined with paclitaxel weekly x 12. Following surgery pts received 3 cycles fluorouracil, epirubicin and cyclophosphamide q 3 weeks. The assigned anti-HER2 treatment was continued for 34 weeks thereafter. Primary endpoint was pCR (ypT0/is), secondary endpoints were EFS and OS and the association between pCR and OS analyzed by landmark analysis 30 weeks after randomization. Median follow-up was 6.7 years. Results: 6-yrs EFS rate was 67%/ 67%/74% with L/T/TL, respectively (L vs T HR 0.98 [95% CI 0.64–1.51] p=0.93; TL vs T HR 0.81 [95% CI 0.52–1.26] p=0.35). In the hormone receptor negative group 6- yrs EFS rate was 61%/ 63%/74% for the 3 groups, respectively (L vs T HR 1.09 [95% CI 0.61–1.95] p=0.76; TL vs T HR 0.81 [95% CI 0.44–1.51] p=0.52). OS at 6 yrs was 82%/79%/85% for L, T and TL, respectively (L vs T: HR 0.85 [95% CI 0.49-1.46] p=0.56; TL vs T HR 0.72 [95% CI 0.41-1.27] p=0.26). In landmark analyses, pts with a pCR had significantly higher 6-yrs EFS (77% /65%) and OS (89% /77%) compared to those without pCR, both overall and for the hormone receptor negative cohort. Conclusions: The updated results of the NeoALTTO study confirm the sustained survival benefits for pts who achieve a pCR. EFS and OS after 6 yrs did not differ significantly between the 3 treatment groups. The combination of T and L showed numerically higher EFS compared to T, especially in the hormone-receptor negative group. Clinical trial information: NCT00553358. [Table: see text]

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Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.510 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 510-510 ◽

Cited By ~ 3

Author(s):

Justin Stebbing ◽

Yauheni Valerievich Baranau ◽

Valery Baryash ◽

Alexey Manikhas ◽

Vladimir Moiseyenko ◽

...

Keyword(s):

Neoadjuvant Treatment ◽

Complete Response ◽

Phase Iii ◽

Efficacy And Safety ◽

Her2 Positive ◽

Double Blind ◽

Secondary Endpoints ◽

Phase Iii Study ◽

To Receive ◽

Related Reaction

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]

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Establishing analytical and clinical similarity between HD201 and herceptin.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.579 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 579-579

Author(s):

Jocelyn Hii ◽

Xavier Pivot ◽

Kristi Mclendon ◽

Kuo Wei Chan ◽

Peggy Feyaerts ◽

...

Keyword(s):

Breast Cancer ◽

Human Subjects ◽

Complete Response ◽

Phase Iii ◽

Her2 Positive ◽

Healthy Human ◽

Double Blind ◽

Clinical Phase ◽

Parallel Group ◽

Eu And Us

579 Background: Trastuzumab, an approved prescription drug by EMA and FDA under the name Herceptin has become the key treatment in patients with HER2−positive breast cancer. HD201, developed by Prestige Biopharma Pte Ltd is a biosimilar candidate to Herceptin. The biosimilarity of HD201 was established based on systematic stepwise comparisons between HD201 and reference product, Herceptin. In order to confirm clinical similarity of HD201 to Trastuzumab, two clinical studies were undertaken. Methods: First, in a double-blind, randomised and parallel group study, 101 randomised healthy human subjects were subjected to a single 6 mg/kg IV dose by body weight over 90-min infusion of either HD201, EU- and US-Herceptin group by assessing pharmacokinetic (PK) and safety (TROIKA-I). The second study was a randomised, double-blind, parallel group, equivalence, multicentre clinical phase III trial (TROIKA) designed to compare the efficacy based on total pathological complete response rate (tpCR), safety, and pharmacokinetics of HD201 to EU-Herceptin in patients with HER2 positive early breast cancer. Each group of ~250 subjects were administered with either HD201 or EU-Herceptin in combination with chemotherapy in neoadjuvant followed by the antibody alone in the adjuvant phase. Results: TROIKA-I study demonstrated that HD201 was safe and well tolerated with comparable PK as EU- and US-Herceptin. Based on the neoadjuvant data from TROIKA study, the tpCR rate in the HD201 and Herceptin treatment groups was comparable and the 95% CI was included within the pre-defined margins of equivalence (Table). The incidence and severity of reported TEAEs did not imply any significant safety concerns and were comparable between both groups. In addition, the comparison of steady-state Ctrough between both arms in TROIKA study has established equivalence. Conclusions: The overall comparison exercise demonstrated the equivalence of HD201 to Herceptin. Clinical trial information: 2016-0040019-11 . [Table: see text]

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Neoadjuvant Pertuzumab plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2 Positive Breast Cancer: Real-World Data from a National Institute of Oncology in Poland.

10.20944/preprints202201.0164.v1 ◽

2022 ◽

Author(s):

Agnieszka Irena Jagiełło-Gruszfeld ◽

Magdalena Rosinska ◽

Malgorzata Meluch ◽

Katarzyna Pogoda ◽

Anna Niwińska ◽

...

Keyword(s):

Breast Cancer ◽

Pathologic Complete Response ◽

Complete Response ◽

Her2 Positive ◽

Real World Data ◽

Cancer Subtypes ◽

Cancer Management ◽

Her2 Positive Breast Cancer ◽

Neoadjuvant Systemic Therapy ◽

Positive Breast Cancer

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

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Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.0126 ◽

2018 ◽

Vol 36 (10) ◽

pp. 968-974 ◽

Cited By ~ 36

Author(s):

Xavier Pivot ◽

Igor Bondarenko ◽

Zbigniew Nowecki ◽

Mikhail Dvorkin ◽

Ekaterina Trishkina ◽

...

Keyword(s):

Breast Cancer ◽

Epidermal Growth Factor Receptor ◽

Adverse Event ◽

Growth Factor ◽

Response Rate ◽

Pathologic Complete Response ◽

Growth Factor Receptor ◽

Complete Response ◽

Phase Iii ◽

Epidermal Growth

Purpose This phase III study compared SB3, a trastuzumab (TRZ) biosimilar, with reference TRZ in patients with human epidermal growth factor receptor 2–positive early breast cancer in the neoadjuvant setting ( ClinicalTrials.gov identifier: NCT02149524). Patients and Methods Patients were randomly assigned to receive neoadjuvant SB3 or TRZ for eight cycles concurrently with chemotherapy (four cycles of docetaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide) followed by surgery, and then 10 cycles of adjuvant SB3 or TRZ. The primary objective was comparison of breast pathologic complete response (bpCR) rate in the per-protocol set; equivalence was declared if the 95% CI of the ratio was within 0.785 to 1.546 or the 95% CI of the difference was within ± 13%. Secondary end points included comparisons of total pathologic complete response rate, overall response rate, event-free survival, overall survival, safety, pharmacokinetics, and immunogenicity. Results Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95% CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively. Conclusion Equivalence for efficacy was demonstrated between SB3 and TRZ on the basis of the ratio of bpCR rates. Safety and immunogenicity were comparable.

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