May 3, 2017 : Episode 1

FDA Approvals in Bladder Cancer, NSCLC, AML, HCC, and a Breakthrough Designation in NSCLC



FDA approvals in bladder cancer, lung cancer, acute myeloid leukemia, and liver cancer, and a breakthrough therapy designation in non—small cell lung cancer.

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

The FDA has granted an accelerated approval to the PD-L1 inhibitor durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy. It is also indicated for patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The VENTANA PD-L1 assay, which is the complementary diagnostic for PD-L1, was also approved.

The approval was based on findings from the phase I/II Study 1108. Here, the objective response rate per blinded independent central review was 17% for patients with locally advanced or metastatic urothelial carcinoma. The ORR was 26.3% in patients with high PD-L1 expression.

The accelerated approval is contingent on the results of confirmatory trial.


In non—small cell lung cancer, the ALK inhibitor brigatinib was approved by the FDA as a treatment for patients with metastatic ALK-positive NSCLC who are resistant to prior crizotinib.

The approval is based on phase II findings from the ALTA trial, in which the 180-mg daily dose of brigatinib was linked with a confirmed objective response rate of 53%. Additionally, the median progression-free survival was 13.8 months.

In patients who received 90 mg of brigatinib, the confirmed ORR was 48%. There were 4 complete responses in the 180-mg arm and 1 in the 90-mg arm.

This accelerated approval is contingent on 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. The study is assessing the 180-mg dose of brigatinib.


The FDA has also granted an approval to midostaurin for the treatment of adult patients with newly diagnosed FLT3-positive acute myeloid leukemia. The agent will be given in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

The companion diagnostic LeukoStrat CDx FLT3 Mutation Assay to test for FLT3 mutations in patients with AML was also approved.

Additionally, the FDA approved midostaurin for the treatment of patients with advanced systemic mastocytosis, including aggressive systemic mastocytosis; systemic mastocytosis with associated hematological neoplasm; and mast cell leukemia.

In the phase III RATIFY trial that led to the FDA approval in AML, the addition of midostaurin to standard chemotherapy led to a 23% reduction in the risk of death versus chemotherapy alone. After censoring for patients who received stem cell transplants, the overall survival benefit with midostaurin remained steady at 25%.

Regarding safety, grade 3 or higher adverse events were found to be similar between the midostaurin and placebo arms. Thirty-seven grade 5 AEs occurred in the trial, which was similar between the 2 arms. This was not found to be statistically significant.


In liver cancer, the multikinase inhibitor regorafenib was approved by the FDA as a second-line treatment for patients who have previously received sorafenib.

Regorafenib’s approval is based on data from the phase III RESORCE trial, which demonstrated a median overall survival of 10.6 months with regorafenib plus best supportive care versus 7.8 months for placebo with best supportive care. This represents a 38% reduction in the risk of death.

The median progression-free survival was 3.1 months in the regorafenib arm versus 1.5 months in the placebo group, representing a 54% reduction in the risk of progression or death.

The median time to progression in the regorafenib group was 3.2 months versus 1.5 months with placebo. The overall response rate with regorafenib was 10.6% compared with 4.1% with placebo.

Regorafenib is also already approved for the treatment of patients with metastatic colorectal cancer and gastrointestinal stromal tumors.


Also in non—small cell lung cancer, the FDA granted a breakthrough therapy designation to lorlatinib for use in patients with ALK-positive metastatic disease who have previously received 1 or more ALK inhibitors.

Lorlatinib is a selective ALK/ROS1 tyrosine kinase inhibitor with significant intracranial activity that is active against more known mutations.

Pfizer, the company developing lorlatinib, submitted results to the FDA from an ongoing phase I/II study. Findings showed that the overall response rate with lorlatinib was 47% with 3 complete responses and 22 partial responses.

The median duration of response was 10.5 months among ALK-positive patients and 12.4 months in patients who are both ALK- and ROS1-positive.

Updated data will be presented at the 2017 ASCO Annual Meeting.


This week, we also sat down with Dr Howard Kaufman of Rutgers Cancer Institute, to shed light on the recent FDA approval of avelumab in Merkel cell carcinoma. ********************************

That’s all for today.

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

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