New Data Show Safety of Ado-Trastuzumab, Trastuzumab Biosimilars in HER2+ Cancers

Posters from the American Society of Clinical Oncology annual meeting showcased safety and efficacy data for a trastuzumab biosimilar and an ado-trastuzumab biosimilar in HER2-positive (HER2+) cancers.

In the phase 2 study concerning a trastuzumab biosimilar, patients with HER2-mutated advanced solid tumors with Herzuma (trastuzumab-pkrb) combined with neratinib, an irreversible pan-HER tyrosine kinase inhibitor.¹

Researchers enrolled 40 patients with HER2 mutated solid tumors, who were treated with 240mg of neratinib administered orally and 8 mg/kg of Herzuma every 3 weeks. The primary end point was the objective response rate (ORR), with secondary end points including duration of response (DoR), progression-free survival (PFS), and safety.

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An exploratory biomarker study was also conducted. With a median follow-up of 11.08 months, patients had a median of 3 prior systemic therapies. Tumor types were primarily lung (42.5%), colorectal (20%), biliary (12.5%), and breast (7.5%).

Among evaluable patients, the ORR was 23.1% (95% CI, 12.7-38.3), with a median DoR of 11.18 (95% CI, 0.0-22.6) months, median PFS of 3.42 (95% CI, 1.57-5.27) months, and median overall survival of 9.47 (95% CI, 2.93-16.01) months. Adverse events that were grade 3 or higher occurred in 47.5% of patients, with diarrhea being the most frequent (25%), followed by bilirubin elevation (5%) and anemia (5%).

The study concluded that the combination therapy showed a moderate response rate and durable response duration, with manageable adverse events, emphasizing the need for proactive diarrhea management. Exploratory biomarker results will be presented at an upcoming meeting.

Another study evaluated the safety and efficacy of a biosimilar of ado-trastuzumab emtansine (Kadcyla; TDM1) in patients with HER2+ breast cancer.² Although the antibody drug conjugate has shown efficacy in treating HER+ breast cancer, the high cost of the reference product limits its use in low- and middle-income countries.

In May 2021, a biosimilar TDM1 was introduced in India, increasing accessibility for patients. The present study retrospectively analyzed the safety and efficacy of biosimilar TDM1 at a single center from June 2021 to October 2023.

Among the 116 patients prescribed biosimilar TDM1, 51 were treated in the adjuvant setting and 65 for advanced-stage disease. In the early-stage group, 32 patients (62.7%) completed the planned cycles, 14 (27.5%) were ongoing, 3 (5.9%) discontinued due to social reasons, and 2 (3.9%) changed treatment due to adverse events. The common adverse effect was fatigue, and 5 patients (21.7%) required romiplostim for therapy-related thrombocytopenia. No patients experienced adverse events that were grade 3 or higher.

In the advanced-stage group, at a median follow-up of 9 months, 30 patients (46.2%) experienced disease progression, 15 (23%) were ongoing, 15 (23%) defaulted due to social reasons, and 5 (7.7%) discontinued due to intolerance. The median number of cycles received was 8 (IQR, 5-13), with most patients (84.6%) receiving TDM1 as second-line therapy. Among 52 patients who completed at least 3 cycles, the ORR was 50.8%, with a clinical benefit rate of 75%. Five patients achieved complete responses (9.6%), 28 experienced partial responses (53.8%), and 6 patients had stable disease (11.5%). The median duration of response was 5 months, median progression-free survival was 8 months (95% CI, 5.7-10.2), and projected overall survival was 18 months (95% CI, 16.1-19.9).

No serious adverse events or cardiac compromise were reported, and thrombocytopenia occurred in 3 patients. One patient died from non-neutropenic septic shock. The study concluded that the availability of biosimilar TDM1 increased access for deserving patients, with safety and efficacy comparable to the original TDM1 and no new adverse events were identified.

References

1. Lee K, Lee K-H, Kim D-W, et al. Phase II study to evaluate safety and efficacy of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, and trastuzumab biosimilar in patients with HER2 mutated advanced solid tumors (KCSG AL20-17). Presented at: ASCO; May 31-June 4, 2024; Chicago, IL. Abstract 3134.

2. Gandrala D, Mallavarapu KMVT, Ayyagari S. Safety and efficacy of biosimilar TDM-1: A real-world retrospective study. Presented at: ASCO; May 31-June 4, 2024; Chicago, IL. Abstract 3022.