Efficacy, safety, and immunogenicity of pertuzumab biosimilar versus reference pertuzumab in combination with trastuzumab and docetaxel in HER2-positive metastatic breast cancer: A randomized, double-blind, multicenter, parallel group, phase III clinical trial.

1047 Background: Pertuzumab plus trastuzumab and docetaxel is a standard first-line treatment regimen for HER2-positive metastatic breast cancer (MBC). This phase III trial evaluated the therapeutic equivalence of pertuzumab biosimilar (manufactured by Intas Pharmaceuticals Ltd., Ahmedabad, India) versus Perjeta when combined with trastuzumab and docetaxel. Methods: This was a randomized (1:1), double-blind, multicenter, parallel-group, phase III equivalence study. Adults with HER2-positive MBC were enrolled and received pertuzumab I.V. (biosimilar or reference product) 840 mg loading dose in cycle 1, then 420 mg every 3 weeks for 24 weeks, in combination with trastuzumab and docetaxel as first-line therapy. Primary endpoint was independently assessed objective response rate (ORR) at week 24 per RECIST v1.1. Secondary endpoints included PFS, OS, duration of response, time-to-event outcomes, pharmacokinetics (T max , C max , AUC 0-t ), safety, and immunogenicity (anti-drug antibodies, ADA). Results: A total of 213 patients were randomized (pertuzumab biosimilar n=106; reference product n=107). ORR at week 24 was comparable between the biosimilar and reference pertuzumab arms: in the mITT set, ORR was 71.3% (72/101) versus 65.0% (67/103), respectively. 6-months PFS rate was 90.1% vs 89.3% in biosimilar and reference pertuzumab arms respectively. Pharmacokinetic parameters (T max , C max , AUC 0-t ) and immunogenecity were comparable between both the arms. Treatment-emergent adverse events (AEs) occurred in 65.1% (pertuzumab biosimilar) and 72.9% (reference product) of patients; most common AEs observed in ≥5% patients in pertuzumab biosimilar vs reference product arm were the following: diarrhea (32.1% vs 30.8%), alopecia (17.0% vs 12.1%), anaemia (8.5% vs 18.7%), vomiting (10.4% vs 11.2%), pyrexia (8.5% vs 10.3%), fatigue (8.5% vs 7.5%), neutropenia (6.6% vs 8.4%), leukopenia (6.6% vs 8.4%), nausea (4.7% vs 7.5%), cough (4.7% vs 5.6%) and headache (3.8% vs 5.6%). Conclusions: Pertuzumab biosimilar demonstrated therapeutic equivalence to reference product in combination with trastuzumab and docetaxel for first-line HER2-positive MBC. Efficacy, safety, pharmacokinetic similarity, and comparable immunogenicity support biosimilarity and its potential as an effective treatment option. Clinical trial information: CTRI/2022/12/048133. Summary statistics for objective response rate (ORR) at week 24 (mITT set, N=204). Parameter Pertuzumab biosimilar (N=101), n (%) Reference product (N=103), n (%) Complete response 4 (4%) 1 (1%) Partial response 68 (67.3%) 66 (64.1%) Overall response rate 72 (71.3%) 67 (65.0%) Difference in ORR (95% CIs) -7.50, 19.97