Clin Cancer Res
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Multicenter Study
FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma.
In October 2017, the FDA granted regular approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Efficacy was based on complete remission (CR) rate and duration of response (DOR) in 101 adult patients with relapsed or refractory large B-cell lymphoma (median 3 prior systemic regimens) treated on a single-arm trial. Patients received a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. ⋯ With a median follow-up of 7.9 months, the median DOR was not reached in patients achieving CR (95% CI, 8.1 months; not estimable, NE), whereas patients with partial remission had an estimated median DOR of 2.1 months (95% CI, 1.3-5.3). Among 108 patients evaluated for safety, serious adverse reactions occurred in 52%. Cytokine release syndrome and neurologic toxicities occurred in 94% and 87% of patients, respectively, leading to implementation of a risk evaluation and mitigation strategy.
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Multicenter Study
FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease.
On March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP ALL. The basis for this accelerated approval was a single-arm trial. ⋯ The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. The FDA is requiring confirmation of clinical benefit in a randomized trial.
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Multicenter Study
A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers.
Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts. ⋯ Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366-73. ©2017 AACR.
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Randomized Controlled Trial Multicenter Study
Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer.
Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase II trial determined whether addition of veliparib to carboplatin and paclitaxel improved progression-free survival (PFS) in previously untreated patients with advanced/metastatic non-small cell lung cancer. ⋯ Conclusions: Veliparib combination with carboplatin and paclitaxel was well-tolerated and demonstrated a favorable trend in PFS and OS versus chemotherapy alone. Patients with squamous histology had the best outcomes with veliparib combination. Clin Cancer Res; 23(8); 1937-44. ©2016 AACR.
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Randomized Controlled Trial Multicenter Study Comparative Study
BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer.
Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open-label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab. ⋯ The efficacy of tivozanib/mFOLFOX6 was comparable with but not superior to bevacizumab/mFOLFOX6 in patients with previously untreated mCRC. Since data from the prespecified interim analysis did not demonstrate superiority, this resulted in discontinuation of the study. The safety and tolerability profile of tivozanib/mFOLFOX6 was consistent with other tivozanib trials. NRP-1 is a potential predictive biomarker for tivozanib activity, but these results require further validation. Clin Cancer Res; 22(20); 5058-67. ©2016 AACR.