Long-term study results show that outcomes, such as survival and response rates, in patients who have received Calquence-containing treatment regimens continue to outpace outcomes in those who were given Gazyva and chemotherapy.
Approximately five years of follow-up data show that Calquence (acalabrutinib) alone or in combination with Gazyva (obinutuzumab) continues to outperform Gazyva combined with the chemotherapy agent chlorambucil in patients with treatment-naïve chronic lymphocytic leukemia (CLL).
In fact, the long-term follow-up data — which were presented at the 2022 American Society of Clinical Oncology Annual Meeting — demonstrate that the Calquence-containing treatment regimens produce more favorable results in both progression-free survival (time a patient is alive without disease getting worse) as well as overall response rate (percentage of patients whose disease partially or completely responds to treatment) at five years.
Previous reporting of the phase 3 ELEVATE-TN trial — at a median follow-up of 28.3 and 46.9 months — have also shown that Calquence with or without Gazyva bests the results provided by Gazyva and chlorambucil in this patient population.
During this year’s conference, Dr. Jeff Sharman, director of Research at Willamette Valley Cancer Institute in Eugene, Oregon, and medical director of Hematology Research at The US Oncology Network, presented the updated findings.
The trial enrolled 535 patients (median age, 70 years) who were randomized to receive either single-agent Calquence (179 patients), Calquence plus Gazyva (179 patients) or the chemoimmunotherapy combination of Gazyva and chlorambucil (177 patients).
If disease progression was confirmed in patients who receive the chemoimmunotherapy combination, those patients were then allowed to crossover to receive the single-agent Calquence regimen.
The main goal of the study authors was to measure progression-free survival. Of note, Sharman explained that at the 58.2-month mark, 59.8% and 64.8% of patients in the Calquence single-agent and Calquence-Gazyva combination groups remained on treatment, respectively. Moreover, 72 patients who started the trial in the chemoimmunotherapy group crossed over to receive single-agent Calquence.
Since the change of treatment regimens, however, 25% of those patients have discontinued single-agent Calquence treatment — 10% of discontinuations were due to the onset of side effects.
As of this reporting, progression-free survival outcomes favor single-agent Calquence (72%) and Calquence plus Gazyva (84%) over the chemoimmunotherapy regimen (21%). Moreover, a median progression-free survival has not yet been reached for either Calquence-treatment group, which is considered a good outcome since it highlights longer survival without disease progression. However, in the treatment group that received Gazyva with chlorambucil, median progression-free survival was 27.8 months.
The findings also demonstrated that the progression-free survival benefit translated to patients who had del(17p) and/or mutated TP53 disease. In this patient population, both the Calquence only and Calquence plus Gazyva group have a progression-free survival rate of 71%. The progression-free survival rate drops significantly to 18% in the chemoimmunotherapy group.
The overall response rate was also significantly higher in both the Calquence plus Gazyva (96.1%) and Calquence only (89.9%) group compared with the chemoimmunotherapy combination group (83.1%). Complete responses (also known as the disappearance of all signs of cancer) also occurred more frequently in the Calquence-containing groups — 32.4% and 14.5% in the Calquence combination and single-agent group, respectively. Whereas 13.6% of patients in the chemoimmunotherapy group achieved a complete response.
“The proportion of patients who achieved a complete response, including those with incomplete blood count recovery, were higher in the acalabrutinib-containing arms,” Sharman said during a pre-recorded presentation of the data. “Minimal residual disease was completed only for those patients who achieved complete response.”
Forty-two percent of the patients who achieved a complete response with Calquence plus Gazyva had undetectable minimal residual disease (which is the presence of a small number of cancer cells in the body), versus 9% of patients in the chemoimmunotherapy arm.
A median overall survival has not yet been reached in any of the treatment groups, according to Sharman. However, he said, the authors have observed longer overall survival in the Calquence plus Gazyva group versus the chemoimmunotherapy group.
In terms of side effects, Sharman said they remained similar to past analyses of the findings. Cardiac events, bleeding and infections were significantly more likely to occur in the Calquence treatment groups However, Sharman noted these were also consistent with what has been previously shown.
“We conclude that acalabrutinib demonstrates durability, tolerability, and flexibility to tailor treatment as monotherapy or in combination with obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia,” he said of the findings.
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