October 4, 2017 : Episode 1

FDA Approvals in Breast Cancer and NSCLC, NDA Accepted in HCC, and More



FDA approvals in breast cancer and non—small cell lung cancer, a priority review designation in breast cancer, a new drug application accepted in hepatocellular carcinoma, a breakthrough therapy designation in Hodgkin lymphoma, and Japanese approvals in Merkel cell carcinoma and multiple myeloma.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved abemaciclib, known by the trade name, Verzenio, for use in combination with fulvestrant in women with hormone receptor-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. The CDK4/6 inhibitor has also been approved as a monotherapy for patients with HR-positive/HER2-negative breast cancer with metastatic disease who have previously received endocrine therapy and chemotherapy.

The decision on the combination approval stems from results of the phase III MONARCH 2 trial, in which adding abemaciclib to fulvestrant reduced the risk of disease progression or death by 45% versus fulvestrant alone. Additionally, the single-agent approval is based on the single-arm phase II MONARCH 1 trial, in which the median progression-free survival in this patient population was 6 months and the median overall survival was 17.7 months.

Following 379 PFS events in the intent-to-treat population in the MONARCH 2 trial, the median PFS was 16.4 months in the abemaciclib arm versus 9.3 months in the fulvestrant-alone group. The overall response rates among patients with measurable disease were 48.1% and 21.3% in the abemaciclib and control arms, respectively.

Moreover, a 48.1% ORR in the abemaciclib cohort included a complete response rate of 3.5%. There were no complete responses in the control arm. The median duration of response was 25.6 months in the placebo arm and had not yet been reached in the fulvestrant arm. OS data are not yet mature.


For patients with non—small cell lung cancer, the FDA has approved a supplemental new drug application for the use of 180-mg tablets of brigatinib.

In April 2017, the FDA granted an accelerated approval to brigatinib as a treatment for patients with metastatic ALK-positive NSCLC who are resistant to prior crizotinib. Brigatinib is approved at a starting dose of 90 mg once daily for 7 days. Patients who tolerate the initial regimen have their dose increased to 180 mg once daily.

Previously, brigatinib was only available in 30- and 90-mg tablets.

Brigatinib’s accelerated approval is contingent upon results from a confirmatory trial. The phase III ALTA-1L study has been initiated to compare brigatinib with crizotinib as a frontline therapy for patients with ALK-positive NSCLC.

Takeda, the manufacturer of brigatinib, reported that updated data from the ALTA trial will be presented at the 18th World Conference on Lung Cancer this month in Japan.


The FDA has accepted a supplemental new drug application for lenvatinib as a frontline systemic treatment for patients with advanced hepatocellular carcinoma. Under a standard review, the FDA will render a decision within 10 months.

The application for lenvatinib was based on results from the phase III REFLECT trial, in which overall survival was found to be noninferior for lenvatinib versus standard sorafenib.

Data showed that the median OS with lenvatinib was 13.6 versus 12.3 months for sorafenib. Lenvatinib was also associated with improvements in progression-free survival, time to progression, and objective response rate compared with sorafenib.

The treatment landscape for patients with HCC has undergone several changes in the past year, starting with the approval of the multikinase inhibitor regorafenib in the second-line setting following sorafenib. Similarly, the PD-1 inhibitor nivolumab was approved as a second-line therapy on September 22, based on findings from the phase I/II CheckMate-040 study.


In early breast cancer, the FDA has granted a priority review to a supplemental biologics license application for pertuzumab for use in combination with trastuzumab and chemotherapy for the adjuvant treatment of patients with HER2-positive disease.

The sBLA is based on data from the phase III APHINITY trial, which demonstrated that patients who received adjuvant pertuzumab with trastuzumab plus chemotherapy had an invasive disease-free survival rate of 94.1% after 3 years’ follow-up versus 93.2% for those who received trastuzumab plus chemotherapy and placebo. At 4 years’ follow-up, the rates were 92.3% versus 90.6%, respectively.

At 3 years, the iDFS rate for patients with node-positive disease was 92.0% with pertuzumab versus 90.2% with standard therapy. At 4 years, the rates were 89.9% and 86.7%, respectively.

APHINITY is also the confirmatory trial for the September 2013 accelerated approval of pertuzumab for use in combination with trastuzumab and docetaxel as a neoadjuvant treatment for patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer.

With the application, Genentech, the manufacturer of pertuzumab, is also seeking to convert the accelerated neoadjuvant approval into a full approval.


The FDA has awarded brentuximab vedotin a breakthrough therapy designation as a first-line treatment for patients with classical Hodgkin lymphoma.

The designation is based on phase III results from the ECHELON-1 trial, in which the 2-year rate of modified progression-free survival for brentuximab vedotin plus AVD was 82.1% compared with 77.2% for patients receiving ABVD.

Results also showed that the experimental combination reduced the risk of disease progression or death by 23%. An interim analysis of 2-year overall survival also showed a trend favoring the brentuximab arm.

The company plans to present full data at the 2017 ASH Annual Meeting in December.


In Japan, the PD-L1 inhibitor avelumab has been approved for use in patients with metastatic Merkel cell carcinoma.

The Japanese Ministry of Health, Labor and Welfare previously awarded Orphan Drug Designation to avelumab in December 2016. Pfizer, the developer of avelumab, noted that this is the first Asian country to approve avelumab.

The approval is based on data from the phase II JAVELIN Merkel 200 study. In Part A of the trial, which included previously treated patients, the objective response rate with avelumab was 33%, which included an 11.4% complete response rate and a 21.6% partial response rate.

In Part B of the trial, which included patients who had not received prior systemic treatment in the metastatic setting, the ORR was 62%, including a CR rate of 14% and PR rate of 48%. The 3-month PFS rate was 67%.

The Japanese Ministry of Health, Labor and Welfare has also approved the use of daratumumab for the treatment of adults with relapsed/refractory multiple myeloma. The indication is for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.

The Japanese approval is primarily based on phase III results from the CASTOR and POLLUX trials.

In the POLLUX trial, the addition of daratumumab to lenalidomide and dexamethasone reduced the risk of progression or death by 63% versus lenalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma. In CASTOR, the addition of daratumumab to bortezomib and dexamethasone reduced the risk of progression or death by 61% versus 2 drugs alone for patients with recurrent or refractory multiple myeloma.


This week, we sat down with Dr Andre Goy of John Theurer Cancer Center to discuss the approval of the chimeric antigen receptor T-cell therapy tisagenlecleucel in acute lymphoblastic leukemia.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.

Related Content