Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses recent advancements with biosimilars.

In December 2017, the FDA approved the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst), which is co-developed by Mylan and Biocon. This biosimilar has indications for HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma. MYL-1401O joined ABP-215 (bevacizumab-awwb; Mvasi), a biosimilar for bevacizumab (Avastin) developed by Amgen and Allergan, which was approved as the first biosimilar in the United States in September 2017.

Rugo says that biosimilars is a game-changing area. The world of generics creates competition, lowering the prices of drugs. Rugo says that once the trastuzumab biosimilar is available in the United States in 2019, more will be known about pricing.

Videos

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses recent advancements with biosimilars.
 

Dr. Rugo Discusses Advancements With Biosimilars

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses ongoing trials for patients with HER2-positive breast cancer.

Physicians are looking to move neratinib (Nerlynx) earlier in the adjuvant course to manage diarrhea with a novel agent, explains Rugo. The FDA approved neratinib in the adjuvant setting in July 2017.

In the metastatic setting, oral tyrosine kinase inhibitors (TKIs) are also showing interest. Additionally, there is a novel antibody called margetuximab (MGAH22-10) currently being investigated in the phase III SOPHIA trial. This showed responses in phase I studies for patients who had disease resistance to trastuzumab (Herceptin). There are a number of different agents that seem to have potential in the future, explains Rugo.

SOPHIA is randomizing patients with HER2-positive metastatic breast cancer who had prior anti-HER2 targeted treatment to receive margetuximab or trastuzumab with physician's choice of chemotherapy.

Dr. Rugo on Ongoing Trials in HER2+ Breast Cancer

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses immunotherapy in triple-negative breast cancer (TNBC).

Immunotherapy agents need to be started earlier in TNBC, says Rugo, as that is where the best response is seen.

As cancers progress, mutational load increases neoantigens. If a tumor has an increased mutational load, the tumor can progress and develop more resistance—creating more mechanisms of avoiding an immune response, which Rugo says are beyond a checkpoint inhibitor.

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses immunotherapy in triple-negative breast cancer. 

Dr. Rugo Discusses Immunotherapy in TNBC

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses late recurrence in patients with hormone receptor (HR)-positive breast cancer.

Rugo says that the idea of latency in HR-positive disease is still not fully understood.

Currently, trials involving CDK4/6 inhibitors and PI3K inhibitors are garnering interest in this population. Rugo says that it remains to be seen whether these agents are the key to understanding late recurrence.

Dr. Rugo Discusses Late Recurrence in HR+ Breast Cancer

Hope Rugo, MD, a professor of Medicine and director of the Breast Oncology Clinical Trials Program at the UCSF Helen Diller Family Comprehensive Cancer Center, discusses MYL-1401O, a proposed biosimilar for trastuzumab (Herceptin), in patients with HER2-positive metastatic breast cancer.

While there were not enough patients in the trial to document safety without a shadow of a doubt, the biosimilar was shown to be very safe, says Hugo. The only toxicities that occurred were related to the chemotherapy andthere were none that could be directly attributed to the antibody. Population pharmacogenetics were also similar. The immunogenicity, or the ability to make anti-drug antibody, was about 2.5% in both arms, which is similar to what has been reported for Herceptin in the past, says Rugo.

Overall the study demonstrated that this proposed trastuzumab biosimilar is really similar and fits the regulatory guidelines. For that reason, Rugo is hopeful that the submission to the regulatory agencies will be successful. In the United States, however the biosimilar will not be used for a while because there is still patent life for Herceptin.

Dr. Hope Rugo on Safety of Trastuzumab Biosimilar for HER2+ Breast Cancer

Hope Rugo, MD, a professor of Medicine and director of the Breast Oncology Clinical Trials Program at the UCSF Helen Diller Family Comprehensive Cancer Center, discusses the Heritage study, which evaluated MYL-1401O, a proposed biosimilar for trastuzumab (Herceptin), in patients with HER2-positive metastatic breast cancer.

 The trial was designed with a primary endpoint of overall response rate (ORR) at 24 weeks. Patients with treatment-naïve metastatic HER2-positive breast cancer were randomized to receive either Herceptin or the proposed trastuzumab biosimilar in combination with a taxane of choice. The institution had to choose their taxane and 75% chose docetaxel and 25% chose paclitaxel, explained Rugo.

In 450 patients with metastatic HER2-positive disease in the first-line setting, response rates were close to equivalent and the hazard ratio fell within an equivalency ratio, said Rugo. The FDA and the European Medicines Agency (EMA) had different requests for the way they wanted to see data. The FDA wanted to look at the ORR ratio, and the EMA wanted to look at the response difference between the two arms. This trial fell well within all of those guidelines, said Rugo.

Hope Rugo, MD

Articles

Dr. Rugo Discusses Advancements With Biosimilars

Dr. Rugo on Ongoing Trials in HER2+ Breast Cancer

Dr. Rugo Discusses Immunotherapy in TNBC

Dr. Rugo Discusses Late Recurrence in HR+ Breast Cancer

Dr. Hope Rugo on Safety of Trastuzumab Biosimilar for HER2+ Breast Cancer

Dr. Hope Rugo on Trastuzumab Biosimilar in HER2-Positive Breast Cancer