Top news of the week in oncology and cancer drug development.
FDA Approves Durvalumab for Bladder Cancer
The FDA has granted an accelerated approval to the PD-L1 inhibitor durvalumab (Imfinzi) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. A complementary diagnostic for PD-L1, the VENTANA PD-L1 (SP263) Assay, was simultaneously approved.
The approval was based on the single-arm phase I/II Study 1108, which included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy. In the study, the objective response rate (ORR) per blinded independent central review was 17.0% (95% CI, 11.9-23.3). At the data cutoff, the median duration of response was not reached (range, 0.9+ to 19.9+ months).
FDA Approves Brigatinib for ALK-Positive NSCLC
The FDA has granted brigatinib (Alunbrig) an accelerated approval as a treatment for patients with metastatic ALK-positive non—small cell lung cancer (NSCLC) who are resistant to prior crizotinib (Xalkori). The approval is based on findings from the phase II ALTA trial, in which the confirmed objective response rate for brigatinib at 180 mg daily was 53% (95% CI, 43-62) and the median progression-free survival (PFS) was 13.8 months.
The confirmed ORR was 48% (95% CI, 39-58) in the 90-mg arm. In those who had not received prior chemotherapy, the ORR was 52%. In the 180-mg dose group, those who had not received chemotherapy had an ORR of 52%. There were 4 confirmed complete responses in the 180-mg arm and 1 in the 90-mg group. The median duration of response was 13.8 months in both arms. The median PFS in the 90-mg arm was 9.2 months. There was a 45% reduction in the risk of progression or death with the 180-mg dose of brigatinib versus the 90-mg dose (HR, 0.55; 95% CI, 0.35-0.86). The 1-year PFS rate was 39% with the 90-mg dose and 54% in the 180-mg arm.
FDA Approves Midostaurin for AML
The FDA has approved midostaurin (Rydapt) for the treatment of adult patients with newly diagnosed FLT3-positive acute myeloid leukemia (AML) in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. The drug has also been approved for the treatment of patients with advanced systemic mastocytosis (SM), including aggressive systemic mastocytosis (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia.
Midostaurin was approved along with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, to test for FLT3 mutations in patients with AML. The approval is based on the phase III RATIFY trial in AML and 2 single-arm, open-label studies of patients with SM. In the RATIFY trial, the addition of midostaurin to standard chemotherapy reduced the risk of death by 23% compared with chemotherapy alone in patients with AML who harbored an FLT3 mutation.
After censoring for patients who received stem cell transplants, the overall survival benefit with midostaurin remained steady at 25%. In the pivotal phase II trial considered for the SM approvals, among patients receiving 6 cycles of midostaurin, the rates of confirmed complete remission (CR) plus incomplete remission (ICR) by modified Valent criteria were 38% for ASM and 16% for SM-AHN. One patient with mast cell leukemia had a CR.
FDA Grants Lorlatinib Breakthrough Designation for NSCLC
The FDA has granted a breakthrough therapy designation to lorlatinib for use in patients with ALK-positive metastatic non-small cell lung cancer who have previously received 1 or more ALK inhibitors, according to Pfizer, the company developing the next-generation ALK/ROS1 tyrosine kinase inhibitor (TKI). The designation was based on findings from the ongoing phase I/II study NCT01970865 (N = 54) presented at the 17th World Conference on Lung Cancer in 2016.
As of January 2016, the study had accrued 41 patients who were ALK-positive, 12 who were ROS1-positive, and the mutation status of 1 patient was not recorded at cutoff. Overall response rate (ORR) was 47%, with 3 compete responses (CR) and 22 partial responses (PR). ORR was 57% for ALK-positive patients with 1 prior TKI treatment (n = 14) with 1 CR (7%) and 7 PRs (50%). For ALK-positive patients with ≥2 prior TKI treatments (n = 26), ORR was 42% with 2 CRs (8%) and 9 PRs (34%).
FDA Approves Regorafenib for Liver Cancer
The FDA has approved regorafenib (Stivarga) as a second-line treatment for patients with hepatocellular carcinoma who have previously received sorafenib (Nexavar). The approval of the multikinase inhibitor is based on the phase III RESORCE trial, in which the median overall survival was 10.6 months with regorafenib plus best supportive care compared with 7.8 months for placebo plus best supportive care, representing a 38% reduction in the risk of death (HR, 0.62; 95% CI, 0.50-0.78; P <.001).
Median PFS was 3.1 months in the regorafenib arm compared with 1.5 months in the placebo group, representing a 54% reduction in the risk of progression or death (HR, 0.46; 95% CI, 0.37-0.56; P <.001). The median time to progression in the regorafenib group was 3.2 versus 1.5 months with placebo (HR, 0.44; 95% CI, 0.036-0.55; P <.001).
Pembrolizumab for Hodgkin Lymphoma
The European Commission has approved pembrolizumab (Keytruda) for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma who have progressed following autologous stem cell transplant and brentuximab vedotin (Adcetris), or who are transplant-ineligible and have failed brentuximab vedotin.
Daratumumab Triplets for Myeloma
The European Commission has approved daratumumab for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of patients with multiple myeloma following at least 1 prior therapy.
Full Approval for Osimertinib in EGFR T790M-Positive NSCLC
The European Union has granted a full approval to osimertinib (Tagrisso) for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non—small cell lung cancer, regardless of prior treatment with an EGFR TKI.