Patients with relapsed and/or refractory peripheral T-cell lymphoma (PTCL) have limited treatment options, and, subsequently, poor survival outcomes. Alisertib, an investigational oral selective inhibitor of Aurora A kinase, may have a place in treating PTCL but has not yet shown superiority over other agents, according to results from an interim analysis of the Lumiere trial.
Alisertib has shown promising anti-tumor activity in previous phase II studies of patients with relapsed and/or refractory PTCL, but this is the first phase III trial to evaluate single-agent alisertib against investigator’s choice in these patients. The results were presented by Owen A. O’Connor, MD, PhD, from the Center for Lymphoid Malignancies at the Columbia University Medical Center at the New York Presbyterian Hospital.
238 patients from 27 countries were randomized 1:1 to receive:
- Alisertib: 50 mg twice daily on days 1-7 in 21-day cycles (n=120)
- Investigator’s choice (n=118), including:
- Pralatrexate: 30 mg/m2 intravenously (IV) once weekly for 6 weeks in 7-week cycles
- Romidepsin: 14 mg/m2 IV on days 1, 8, and 15 in 28-day cycles
- Gemcitabine: 1,000 mg/m2 IV on days 1, 8, and 15 in 28-day cycles
All patients included in the study had previously taken one or more conventional systemic cytotoxic therapies, had measurable disease according to the 2007 International Working Group criteria, had a tumor biopsy for central hematopathology review, and had an Eastern Cooperative Oncology Group performance status of 0-2.
Patients received treatment for two years or until disease progression or unacceptable toxicity, though patients could continue treatment past two years if a benefit was shown.
Patients taking alisertib were followed for a median of 9.5 months while those in the comparator regimens were followed for a median of 9.2 months. As seen in TABLE, ORR was lower among those taking alisertib, for an odds ratio (OR) of 0.65 (95% CI 0.34-1.23). Median overall survival (OS) was also shorter among patients receiving alisertib compared with the investigator’s choice of treatment: 9.2 months and 12.2 months (hazard ratio [HR] = 0.901; 95% CI 0.607-1.337).
Median progression-free survival, though, was similar among both groups: 3.7 months for the alisertib cohort versus 3.4 months for the comparator cohort (HR=0.939; 95% CI 0.681-1.293).
Treatment duration was longer in patients receiving alisertib than with the other cohorts (12 weeks vs. 10 weeks, respectively), with 15 percent and 5 percent of patients remaining on treatment after two years.
Grade 3 or higher adverse events occurring in the alisertib versus comparator cohorts included, respectively:
- Neutropenia (44% vs. 27%)
- Thrombocytopenia (29% vs. 27%)
- Anemia (30% vs. 11%, respectively)
“While alisertib showed activity in relapsed/refractory PTCL, there was no significant efficacy benefit versus the comparators,” the authors concluded. Although final results are pending, “based on these interim data, there was a low probability of claiming superiority of alisertib for PFS at the final analysis.”
O’Connor OA, Ozcan M, Jacobsen ED, et al. First multicenter, randomized phase 3 study in patients (pts) with relapsed refractory (R/R) peripheral T-cell lymphoma (PTCL): alisertib (MLN8237) versus investigators choice (Lumiere trial; NCT01482962). Abstract #341. Presented at the 2015 ASH Annual Meeting, December 6, 2015; Orlando, Florida.
|TABLE. Comparison of Efficacy of Alisertib and Investigator’s Choice|
|Pralatrexate (n=40)||Romidepsin (n=17)||
|34 (43%)||16 (40%)||10 (59%)||
|20 (25%)||10 (25%)||5 (29%)||5 (22%)|
|14 (17%)||14 (18%)||6 (15%)||5 (29%)||
|18 (23%)||13 (33%)||2 (12%)||
|27 (34%)||11 (28%)||4 (24%)||
|ORR=objective response rate; PFS=progression-free survival|