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An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
An open-label randomized phase 3 trial of oral alisertib for relapsed/refractory peripheral T-cell lymphoma (rrPTCL) was terminated in 2015 after it became clear that it was not going to prove significantly superior to options already on the market.
A new report explains what happened. Oral Alisertib was compared to two agents approved for rrPTCL: intravenous pralatrexate (Folotyn) and romidepsin (Istodax), as well as a common off-label option, intravenous gemcitabine (Gemzar). In all, 138 adults were randomized to alisertib 50 mg two times per day on days 1-7, with a median of four 21-day cycles; 133 were randomized to a comparator, the majority to gemcitabine, and again with repeated cycles as tolerated (J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899).
Overall response rate (ORR) was 33% for alisertib versus 45% for the comparator arm (odds ratio, 0.60; 95% confidence interval, 0.33-1.08). Median progression-free survival was 115 days for alisertib versus 104 days for the comparators, a non–statistically significant difference (hazard ratio, 0.87; 95% CI, 0.637-1.178). Median overall survival was 415 days in the alisertib arm versus 367 days in the comparator arm, also not statistically significant (HR, 0.98; 95% CI, 0.707-1.369).
In patients with rrPTCL, alisertib “did not demonstrate superior efficacy over comparators,” concluded investigators led by oncologist Owen A. O’Connor, MD, PhD, of the Columbia University Medical Center, New York.
Another downside to this drug is that it was associated with adverse events in more than half of patients who took it. While 53% of alisertib patients developed anemia and 47% became neutropenic, in the comparator arm, only 34% and 31% developed anemia and neutropenia, respectively. Further, three deaths in the trial were judged to have be related to alisertib. An additional two deaths occurred in this trial; those were judged to have been related to the rival treatments.
Despite alisertib’s less than great results, the story of this drug’s use for rrPTCL may not be over.
There were hints of benefits for rrPCLT, which might play out in a more focused trial, maybe “in a subgroup of patients with PTCL who responded poorly to comparator agents,” perhaps as a last ditch option. There’s also “potential for treatment combinations of alisertib with novel agents,” the investigators said.
The ORR differences were driven mostly by better performance with the approved agents: ORR was 61% with romidepsin and 43% with pralatrexate; however, alisertib’s ORR (33%) was similar to that for gemcitabine (35%) with “the potential benefits of ... oral administration,” the researchers said.
Also, the number of patients who discontinued treatment because of adverse events was higher in the comparator arm (14%) than in the alisertib group (9%), and more comparator patients required dose reductions (33% versus 28%) because of drug side effects.
Alisertib binds to and inhibits Aurora A kinase (AAK), which is essential for mitosis; studies have demonstrated overexpression in PTCL, which supports AAK inhibition as a novel therapeutic strategy. Research on alisertib for other cancer indications continues, including breast and lung cancer and leukemia.
Most of the subjects in both study arms were white, and about two-thirds were men; the median age was 63 years in both arms.
The work was funded by alisertib maker Millennium Pharmaceuticals, a subsidiary of Takeda. Dr. O’Connor and other investigators reported various ties to Millennium and Takeda, including research funding, honoraria, and consulting work. The study included employees of the companies.
SOURCE: O’Connor OA et al. J Clin Oncol. 2019 Feb 1. doi: 10.1200/JCO.18.00899.
FROM THE JOURNAL OF CLINICAL ONCOLOGY