ASCO 2016-FIRST TRASTUZUMAB BIOSIMILAR

CHICAGO — A biosimilar to trastuzumab (Herceptin, Genentech/Roche) could be coming soon. The product, Myl-1401O (Mylan NV), has efficacy and safety comparable to the branded product, according to new findings presented here at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

Results from a large randomized phase 3 trial, known as HERITAGE, show that response rates in breast cancer patients treated with trastuzumab were comparable to those in patients treated with Myl-1401O. At 24 weeks, objective response rates were 69.6% with Myl-1401O and 64.0% with trastuzumab.

"This is one of the first trials with biosimilars in oncology to demonstrate similar efficacy, safety, and immunogenicity against the reference product," said lead study author Hope S. Rugo, MD, professor of medicine at the University of California, San Francisco.

"Myl-1401O has the potential to meet the need for an affordable treatment option for patients with HER2-positive cancers," said Dr Rugo, who presented the findings during a press briefing.

"Many biologics are losing patent protection soon, and biosimilars have the potential to significantly improve access to expensive agents," she explained.

No oncologic biosimilars have yet received regulatory approval in the United States or Europe, although ongoing clinical trials are investigating biosimilars of other cancer agents, including rituximab (Rituxan) and bevacizumab (Avastin).

But there have been a couple of biosimilar approvals in the United States.

In March 2015, the recombinant colony-stimulating factor filgrastim-sndz (Zarxio, Sandoz/Novartis) was approved by the US Food and Drug Administration (FDA), making it the first biosimilar to enter the American market. It was approved as a biosimilar to Neupogen (Amgen), a supportive-care drug with several cancer indications, including for patients undergoing myelosuppressive chemotherapy or bone marrow transplantation.

A second biosimilar, a version of infliximab (Remicade, Janssen Biotech) called infliximab-dyyb (Inflectra, Janssen Biotech), for use in the treatment of gastrointestinal disorders, rheumatoid arthritis, and most conditions indicated for its predecessor, was approved by the FDA in April.

All End Points Met

HERITAGE is a randomized multicenter clinical trial that compared the efficacy and safety of Myl-1401O with trastuzumab in 500 treatment-naïve patients with HER2-positive metastatic breast cancer.

Patients received either Myl-1401O or trastuzumab with docetaxel or paclitaxel (investigator choice) for a minimum of eight cycles, and trastuzumab was continued until progression.

Of this group, 44% had hormone-receptor-positive metastatic breast cancer and 84% received docetaxel.

The primary end point was overall response rate (ORR) at week 24; secondary end points included progression-free survival, overall survival, and safety.

For approval, the FDA requires that the primary end point be the ORR ratio, whereas the European Medicines Agency requires that it be the ORR difference, Dr Rugo explained.

The ratio of ORR was 1.09 and the difference in the ORR was 5.5; these results confirm efficacy equivalence.

Median progression-free survival has not been reached. To date, there have been 41 events in the Myl-1401O group and 48 in the trastuzumab group.

The overall drug antibody rate in the Myl-1401O group was 2.4% and in the trastuzumab group was 2.8%, which is consistent with published trastuzumab data showing a low immunogenic potential, Dr Rugo reported.

Safety was comparable, with 38.1% of patients in the Myl-1401O group and 36.2% in the trastuzumab group reporting at least one serious adverse event. Adverse events were primarily hematologic, and included neutropenia (27.5% vs 25.2%), febrile neutropenia (4.5% vs 4.1%), and leukemia (1.6% vs 4.9%).

In response to a question about the relatively short follow-up period of 24 weeks, Dr Rugo pointed out that a version of Myl-1401O has already been approved in India, which has different regulatory laws.

It has been used there safely for a while by patients without access to trastuzumab. "There is actually quite a substantial body of safety data for this agent," she explained.

"These results are incredibly exciting and broaden the access to what has really been a life-saving agent for HER2-positive breast cancer," said press briefing moderator Don Dizon, MD, who is chair of the ASCO Cancer Communications Committee.

This study received funding by Mylan. Dr Rugo reports financial relationships with Celsion, Eisai, Genomic Health, GlaxoSmithKline, Lilly, Macrogenics, Merck, Mylan, Nektar, Novartis, OBI Pharma, Pfizer, Plexxikon, and Roche/Genentech. Some of her coauthors report relationships with industry, as noted in the abstract.

American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract LBA503. To be presented June 6, 2016.