Hans-Christian Kolberg, MD
The pathologic complete response (pCR) rate associated with the trastuzumab (Herceptin) biosimilar ABP 980 was equivalent to that of reference trastuzumab based on central laboratory evaluation in patients with HER2-positive early breast cancer enrolled in the phase III LILAC study.1
Amgen issued a brief statement May 31 announcing that it had received a compete response letter from the FDA for ABP 980.2
The letter means that the agency has rejected the biologics license application Amgen and its partner Allergan submitted in July 2017.
“We will work closely with the FDA to bring this important medicine to patients in the US,” the company said. “We do not expect this to impact our U.S. launch plan.” As assessed by central laboratory review, 162 of 338 patients (47.8%) randomized to ABP 980 achieved a pCR compared with 138 of 330 patients (41.8%) randomized to reference trastuzumab, lead author Hans-Christian Kolberg, MD, reported at the 2018 ASCO Annual Meeting.
The finding adds support to an equivalence claim of ABP 980, which previously demonstrated similarity to the reference product with respect to safety and efficacy in LILAC (NCT01901146), with no clinically meaningful differences between the two products, said Kolberg, head, Department of Obstetrics and Gynecology, Breast Cancer Center, and Gynecologic Cancer Center at Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe, Bottrop, Germany.
The study demonstrates the feasibility of including central pathology review of pCR rates in a large multicenter, multinational study, he added. “When doing studies on biosimilars, you have to decide on at least one endpoint, and if that endpoint is showing clinical efficacy within the same margins, then you can extrapolate that this medication will also be working in gastric cancer and metastatic breast cancer, for which trastuzumab also has indications,” he said.
“We believe that the pCR rate is proving the clinical similarity of the biosimilar,” Kolberg went on to say. “The pCR is a very robust endpoint. It was chosen because pCR is an accepted endpoint in neoadjuvant studies and is also used by the FDA for approval for many new medications. Pertuzumab was approved on pCR data in the beginning.”
Following run-in chemotherapy with epirubicin and cyclophosphamide, patients with adequate cardiac function were randomly assigned to neoadjuvant ABP 980 with paclitaxel versus trastuzumab and paclitaxel every 3 weeks for 4 cycles. Patients continued to the adjuvant phase on ABP 980 for up to 1 year. Data from the adjuvant phase were not included the ASCO presentation.
LILAC was conducted at 97 centers in 20 countries in Europe and other regions. In addition to evaluation of tumor samples by a local pathologist, each sample was evaluated by 2 independent central pathologists.
The coprimary endpoints were risk difference (RD) and risk ratio (RR) of pCR in breast tissue and axillary lymph nodes of tumor samples based on local laboratory evaluation. The criteria for clinical similarity were met if the 2-sided 90% CIs for RD and RR were within the bioequivalence margin of -13% to 13% for RD and 0.759 to 1.318 for RR.
As presented previously at the 2017 ESMO Congress, according to local review, 48.0% of patients in the ABP 980 arm and 40.5% in trastuzumab arm achieved pCR. Risk difference of pCR was 7.3% (90% CI, 1.2-13.4) and RR of pCR was 1.19 (90% CI, 1.033-1.366), with the upper bound confidence interval slightly exceeding the equivalence margin.3
Based on central independent review, the RD of pCR was 5.8% (90% CI, -0.5 to 12.0) and RR of pCR was 1.14 (90% CI, 0.993-1.312), which fell within the equivalence margin.
The incidence of any-grade adverse events (AEs) was 80.2% with BP 980 and 79.5% with trastuzumab, and the rates of grade ≥3 AEs were 14.8% vs. 14.1%, respectively. Rates of arthralgia (17.3% vs. 15.2%), asthenia (14.8% vs. 16.3%), neutropenia (14.6% vs. 12.5%), peripheral neuropathy (13.7% vs. 11.9%), and anemia (11.0% vs. 10.2%) were similar between the two arms.
In March, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion for ABP 980 to treat patients with HER2-positive metastatic breast cancer, HER2-positive early breast cancer, and HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction.
<<< 2018 ASCO Annual Meeting
- Kolberg HC, Tomasevic Z, Demetriou G, et al. Efficacy analyses of central laboratory pCR results from the LILAC study comparing the biosimilar ABP 980 and trastuzumab. J Clin Oncol 36, 2018 (suppl; abstr 583).
- Amgen statement on complete response letter from the U.S. FDA for ABP 980, a biosimilar candidate to Herceptin® (Trastuzumab). Thousand Oaks, CA. Amgen; May 31, 2018. https://wwwext.amgen.com/media/our-perspective/amgen-statement-on-complete-response-letter-from-the-us-fda-for-abp-980/. Accessed June 5, 2018.
- von Minckwitz G, Ponomarova O, Morales S, et al. Efficacy and safety of biosimilar ABP 980 compared with trastuzumab in HER2-positive early breast cancer. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract 151PD.